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GABA B receptors (GABABRs) are heterodimeric seven-transmembrane receptors that interact with a range of proteins and form large protein complexes on cholesterol-rich membrane microdomains. As the brain ages, membrane cholesterol levels exhibit alterations, although it remains unclear how these changes impact protein-protein interactions and downstream signaling. Herein, we studied the structural bases for the interaction between GABABR and the KCC2 transporter, including their protein expression and distribution, and we compared data between young and aged rat cerebella. Also, we analyzed lipid profiles for both groups, and we used molecular dynamics simulations on three plasma membrane systems with different cholesterol concentrations, to further explore the GABABR-transporter interaction. Based on our results, we report that a significant decrease in GABAB2 subunit expression occurs in the aged rat cerebella. After performing a comparative co-immunoprecipitation analysis, we confirm that GABABR and KCC2 form a protein complex in adult and aged rat cerebella, although their interaction levels are reduced substantially as the cerebellum ages. On the other hand, our lipid analyses reveal a significant increase in cholesterol and sphingomyelin levels of the aged cerebella. Finally, we used the Martini coarse-grained model to conduct molecular dynamics simulations, from which we observed that membrane cholesterol concentrations can dictate whether the GABABR tail domains physically establish G protein-independent contacts with a transporter, and the timing when those associations eventually occur. Taken together, our findings illustrate how age-related alterations in membrane cholesterol levels affect protein-protein interactions, and how they could play a crucial role in regulating GABABR's interactome-mediated signaling. Significance Statement: This study elucidates age-related changes in cerebellar GABAB receptors (GABABRs), KCC2, and plasma membrane lipids, shedding light on mechanisms underlying neurological decline. Molecular dynamics simulations reveal how membrane lipids influence protein-protein interactions, offering insights into age-related neurodegeneration. The findings underscore the broader impact of cerebellar aging on motor functions, cognition, and emotional processing in the elderly. By elucidating plasma membrane regulation and GABAergic dynamics, this research lays the groundwork for understanding aging-related neurological disorders and inspires further investigation into therapeutic interventions.

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Background: Some clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro- and anti-inflammatory mediators depending on the clinical setting. Aim: To evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH. Methods: Before-after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1- and M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification. Results: Twenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body-mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1- and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers. Conclusion: PCSK9i therapy exerted subclinical anti-inflammatory and anti-atherogenic effects, indicating potential benefits for clinical outcomes.

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PURPOSE: Nut-enriched diets are related to improve lipid and inflammatory biomarkers in meta-analyses in the context of primary cardiovascular prevention. However, primary studies on secondary cardiovascular prevention are scarce and controversial. This systematic review and meta-analysis aimed to evaluate the effect of nut supplementation on lipid and inflammatory profiles in individuals with atherosclerotic cardiovascular disease, and the frequency of adverse events. METHODS: Six databases were used for research: PubMed, EMBASE, BVS, Cochrane Library, Web of Science, and ClinicalTrials.gov, until February 2023, with no language restrictions. We performed random-effects meta-analyses to compare nut-enriched diets vs. control diets for pre-post intervention changes. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessed the evidence's certainty. RESULTS: From the 5187 records identified, eight publications containing data referring to five randomized clinical trials involving 439 participants were included in the final analyses. The nuts evaluated were almonds, pecans, Brazil nuts, and mixed nuts, with doses ranging between 5 g and 85 g (median: 30 g/day). The intervention time varied between 6 and 12 weeks. Compared to nut-free diets, nut intake did not have a statistically significant effect on lipid profile biomarkers, except on the atherogenic index (MD: -0.32 [95% CI -0.58 to -0.06], I2 = 0% - moderate certainty of the evidence). Similarly, there was no effect of nuts on inflammatory profile biomarkers. It was not possible to aggregate data on adverse events. CONCLUSIONS: Nut supplementation did not change lipid and inflammatory profiles in the secondary cardiovascular prevention setting.

Assuntos

Aterosclerose , Biomarcadores , Inflamação , Lipídeos , Nozes , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Biomarcadores/sangue , Aterosclerose/sangue , Aterosclerose/prevenção & controle , Lipídeos/sangue , Inflamação/sangue , Dieta/métodos , Doenças Cardiovasculares/prevenção & controle

RESUMO

This study aimed to investigate the effects of meat biofortified with antioxidants and canola oil on the health of older adults through blood parameters. Eighty institutionalized older persons were divided into four groups who received the following treatments: C-control meat with 46 µg/kg of meat with selenium, 3.80 g/kg of meat with vitamin E and 0.78 g/100 g of meat with conjugated linoleic acid (CLA); A-antioxidant meat with 422 µg/kg of meat with selenium, 7.65 g/kg of meat with vitamin E and 0.85 g/100 g of meat with CLA; O-oil meat with 57 µg/kg of meat with selenium, 3.98 g/kg of meat with vitamin E and 1.27 g/100 g of meat with CLA; OA-oil and antioxidant meat with 367 µg/kg of meat with selenium, 7.78 g/kg of meat with vitamin E and 1.08 g/100 g of meat with CLA. Blood samples were collected at 0, 45 and 90 days after the start of meat intake. Older adults who consumed ANT (A and AO) meat had higher concentrations of selenium (p = 0.039), vitamin E and HDL (higher concentrations of high-density lipoprotein, p = 0.048) in their blood. This study demonstrates that the consumption of Se- and vitamin E-biofortified meat increases the concentration of these metabolites in blood from older adults.

Assuntos

Antioxidantes , Alimentos Fortificados , Carne Vermelha , Selênio , Vitamina E , Humanos , Masculino , Selênio/sangue , Selênio/administração & dosagem , Idoso , Feminino , Vitamina E/sangue , Antioxidantes/análise , Idoso de 80 Anos ou mais , Óleo de Brassica napus , Animais , Ácidos Linoleicos Conjugados/sangue , Ácidos Linoleicos Conjugados/administração & dosagem , Bovinos , Biofortificação

RESUMO

PURPOSE OF REVIEW: This review aims to critically examine how VLCKD affects plasma lipoprotein, lipid and cholesterol metabolism. Cardiovascular disease is a worldwide health problem affecting millions of people and leading to high rates of mortality and morbidity. There is a well-established association between cardiovascular disease and circulating cholesterol. Various dietary recommendations are currently available for the management of dyslipidemia. RECENT FINDINGS: The very low-calorie ketogenic diet (VLCKD) is becoming increasingly popular as a treatment option for several pathological conditions, including dyslipidemia. In addition to being low in calories, the VLCKD's main feature is its unique calorie distribution, emphasizing a reduction in carbohydrate consumption in favor of fat as the primary calorie source. Lowering calorie intake through a VLCKD can reduce the endogenous production of cholesterol. However, if the foods consumed are from animal sources, dietary cholesterol intake may increase due to the higher fat content of animal products. When combined, these dietary practices may have opposing effects on plasma cholesterol levels. Studies investigating the impact of VLCKD on plasma cholesterol and low-density lipoprotein cholesterol levels report contradictory findings. While some studies found an increase in low-density lipoprotein cholesterol levels, others showed a decrease in total cholesterol and low-density lipoprotein cholesterol, along with an increase in high-density lipoprotein cholesterol.

Assuntos

Restrição Calórica , Dieta Cetogênica , Metabolismo dos Lipídeos , Humanos , Dislipidemias/dietoterapia , Colesterol/sangue , Ingestão de Energia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/dietoterapia , Colesterol na Dieta , LDL-Colesterol/sangue

RESUMO

AIM: To determine the association between atherogenic markers, such as total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL-C), triglycerides/HDL-C ratio (TG/HDL-C), and triglycerides-glucose index (TyG), and the risk of 1-year amputation in adults with diabetic foot in a tertiary level hospital. METHODS: Retrospective cohort study conducted in 162 adult patients with diabetic foot. The outcome was amputation, defined as "primary amputation in patients' clinical history after their first hospitalization due to foot ulcer.". The cutoff point was determined using Youden's J statistic. The relative risk (RR) was presented as an association measure. RESULTS: A TyG index of >9.4 [RR: 1.64 (1.10-2.45)] was associated with a high risk of amputation after 1-year in adults with diabetic foot. However, while a TC/HDL ratio of >4.69 [RR: 1.38 (0.94-2.03)] and a TG/HDL-C ratio > 3.57 [RR: 1.35 (0.89-2.06)] did not show associations with risk of amputation after 1-year. CONCLUSIONS: Only a TyG index of >9.4 was associated with an increased risk of 1-year amputation in adults with diabetic foot. Future studies with larger samples and a longitudinal design may provide more robust evidence and a better understanding of clinical implications.

Assuntos

Amputação Cirúrgica , Biomarcadores , Pé Diabético , Centros de Atenção Terciária , Humanos , Pé Diabético/cirurgia , Pé Diabético/sangue , Pé Diabético/epidemiologia , Amputação Cirúrgica/estatística & dados numéricos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Centros de Atenção Terciária/estatística & dados numéricos , Biomarcadores/sangue , Estudos de Coortes , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/cirurgia , Aterosclerose/complicações , Fatores de Risco , Triglicerídeos/sangue , HDL-Colesterol/sangue , Adulto , Glicemia/análise , Glicemia/metabolismo

RESUMO

Testicular ischemia is one of the most rarely reported complications of endovascular abdominal aortic aneurysm repair (EVAR). Although the pathogenesis remains unclear, thromboembolic events in the setting of testicular artery origin occlusion by the stent graft and poor baseline collateral testicular circulation are presumed causes. A 73-year-old man developed acute right testicular infarction 3 days after EVAR, requiring orchiectomy. This case emphasizes the importance of recognizing and evaluating testicular pain after EVAR and counseling patients on this possible EVAR complication.

RESUMO

Fatty acid profile, physicochemical composition, and carcass traits of 32 young Nellore bulls were assessed following the supplementation of Acacia mearnsii extract at levels of 0, 10, 30, and 50 g/kg of total dry matter (DM) in a completely randomized experiment with four treatments and eight replicates. Adding 50 g/kg DM of condensed tannins (CT) from Acacia mearnsii in the bulls' diet reduced DM intake, average daily gain, and meat lipid oxidation (P ≤ 0.05). The pH, centesimal composition, collagen, and meat color indexes of the longissimus muscle were not altered by the addition of Acacia mearnsii (P > 0.05). Cooling loss increased (P = 0.049) linearly. Including Acacia mearnsii in diet reduced the Warner-Bratzler shear force (WBSF, P = 0.018) of longissimus muscle of the bulls. The concentration of C16:0, C17:0, C24:0, t9,10,11,16-18:1, c9t11-18:2, C18:2n-6, C20:4n-6, 20:5n-3, 22:5n-3, and 22:6n-3 in the muscle increased due to the addition of Acacia in the diet (P ≤ 0.05), with the highest muscle concentrations caused by the addition of 10 to 30 g Acacia. c9-18:1 and t16-18:1 reduced linearly. Æ©SFA, Æ©BI, Æ©cis- and Æ©MUFA, Æ©n-3, Æ©n-6, and Æ©PUFA (P ≤ 0.05) quadratically increased at higher concentrations of addition of Acacia, above 30 g/kg DM. It is recommended to include Acacia mearnsii extract up to 30 g/kg total DM in diets for young bulls as it improves CLA, PUFA and TI and reduces lipid oxidation. Acacia mearnsii extract as source of CT at 50 g/kg DM negatively impacted the young bulls performance.

Assuntos

Acacia , Ração Animal , Dieta , Ácidos Graxos , Músculo Esquelético , Extratos Vegetais , Carne Vermelha , Animais , Bovinos , Acacia/química , Masculino , Carne Vermelha/análise , Músculo Esquelético/química , Ração Animal/análise , Ácidos Graxos/análise , Dieta/veterinária , Extratos Vegetais/química , Cor , Resistência ao Cisalhamento , Suplementos Nutricionais

RESUMO

BACKGROUND: Adiposity favors several metabolic disorders with an exacerbated chronic pro-inflammatory status and tissue damage, with high levels of plasminogen activator inhibitor type 1 (PAI-1) and proprotein convertase subtilisin/kexin type 9 (PCSK9). OBJECTIVE: To demonstrate the influence of bariatric surgery on the crosstalk between PAI-1 and PCSK9 to regulate metabolic markers. METHODS: Observational and longitudinal study of 190 patients with obesity and obesity-related comorbidities who underwent bariatric surgery. We measured, before and after bariatric surgery, the anthropometric variables and we performed biochemical analysis by standard methods (glucose, insulin, triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C] and TG/HDL-C ratio, PAI-1 and PCSK9 were measured by ELISA). RESULTS: PAI-1 levels decreased significantly after bariatric surgery, and were positively correlated with lipids, glucose, and TG, with significance on PCSK9 and TG/HDL-C alleviating the insulin resistance (IR) and inducing a state reversal of type 2 diabetes (T2D) with a significant decrease in body weight and BMI (p <0.0001). Multivariate regression analysis predicted a functional model in which PAI-1 acts as a regulator of PCSK9 (p <0.002), TG (p <0.05), and BMI; at the same time, PCSK9 modulates LDL-C HDL-C and PAI-1. CONCLUSIONS: After bariatric surgery, we found a positive association and crosstalk between PAI-1 and PCSK9, which modulates the delicate balance of cholesterol, favoring the decrease of circulating lipids, TG, and PAI-1, which influences the glucose levels with amelioration of IR and T2D, demonstrating the crosstalk between fibrinolysis and lipid metabolism, the two main factors involved in atherosclerosis and cardiovascular disease in human obesity.

Assuntos

Cirurgia Bariátrica , Obesidade , Inibidor 1 de Ativador de Plasminogênio , Pró-Proteína Convertase 9 , Humanos , Inibidor 1 de Ativador de Plasminogênio/sangue , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Pró-Proteína Convertase 9/sangue , Pró-Proteína Convertase 9/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Obesidade/cirurgia , Obesidade/metabolismo , Obesidade/sangue , Estudos Longitudinais , Resistência à Insulina , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/cirurgia , Triglicerídeos/sangue , Triglicerídeos/metabolismo

RESUMO

Introduction: The behavior of periodontal clinical indicators in metabolic syndrome (MetS) and fatty liver disease (NAFLD) are not clearly defined. It's even considered that high-risk cases for NAFLD are currently underreported or not identified in a timely manner. The aim of the study is to elucidate the interaction of periodontal clinical indicators in MetS and NAFLD. Materials and methods: 336 patients were eligible because they met the diagnostic criteria for metabolic syn-drome and nonalcoholic fatty liver disease. Those selected were randomly selected for a cross-sectional study. Metabolic status and non-alcoholic fatty liver disease were measured using the MetS Metabolic Syndrome Diagnostic Criteria (NCEP/ATP-III) and laboratory tests, respectively. In addition, periodontal clinical indicators were evaluated: probing depth, clinical attachment, plaque index and gingival bleeding. Results: The association for NAFLD and probing depth was p = 0.736. The association for MetS and probing depth was p = 0.598. For NAFLD and clinical attachment loss, the association was p = 0.751. For MetS and clinical attachment loss, the association was p = 0.435. The plaque index for MetS was p = 0.238. The plaque index for NAFLD was p = 0.269. The gingival bleeding association for NAFLD was p = 0.673 and for MetS was p = 0.522. Conclusions: Periodontal clinical indicators of metabolic syndrome were as-sociated with elevated serum levels of low-density lipoproteins (LDL), HDL-cholesterol, and triglycerides. However, when comparing the values in NAFLD and MetS, a greater significance is evident in the first study group.

RESUMO

In this study, we evaluated the impact of incorporating diblock and triblock amphiphilic copolymers, as well as cholesterol into DPPC liposomes on the release of a model molecule, calcein, mediated by exogenous phospholipase A2 activity. Our findings show that calcein release slows down in the presence of copolymers at low concentration, while at high concentration, the calcein release profile resembles that of the DPPC control. Additionally, calcein release mediated by exogenous PLA2 decreases as the amount of solubilized cholesterol increases, with a maximum between 18 mol% and 20 mol%. At concentrations higher than 24 mol%, no calcein release was observed. Studies conducted on HEK-293 and HeLa cells revealed that DPPC liposomes reduced viability by only 5% and 12%, respectively, after 3 hours of incubation, while DPPC liposome in presence of 33 mol% of Cholesterol reduced viability by approximately 11% and 23%, respectively, during the same incubation period. For formulations containing copolymers at low and high concentrations, cell viability decreased by approximately 20% and 40%, respectively, after 3 hours of incubation. Based on these preliminary results, we can conclude that the presence of amphiphilic copolymers at low concentration can be used in the design of new DPPC liposomes, and together with cholesterol, they can modulate liposome stabilization. The new formulations showed low cytotoxicity in HEK-293 cells, and it was observed that calcein release depended entirely on PLA2 activity and the presence of calcium ions.

RESUMO

Cholesterol is crucial for the proper functioning of eukaryotic cells, especially neurons, which rely on cholesterol to maintain their complex structure and facilitate synaptic transmission. However, brain cells are isolated from peripheral cholesterol by the blood-brain barrier and mature neurons primarily uptake the cholesterol synthesized by astrocytes for proper function. This study aimed to investigate the effect of aging on cholesterol trafficking in astrocytes and its delivery to neurons. We found that aged astrocytes accumulated high levels of cholesterol in the lysosomal compartment, and this cholesterol buildup can be attributed to the simultaneous occurrence of two events: decreased levels of the ABCA1 transporter, which impairs ApoE-cholesterol export from astrocytes, and reduced expression of NPC1, which hinders cholesterol release from lysosomes. We show that these two events are accompanied by increased microR-33 in aged astrocytes, which targets ABCA1 and NPC1. In addition, we demonstrate that the microR-33 increase is triggered by oxidative stress, one of the hallmarks of aging. By coculture experiments, we show that cholesterol accumulation in astrocytes impairs the cholesterol delivery from astrocytes to neurons. Remarkably, we found that this altered transport of cholesterol could be alleviated through treatment with endocannabinoids as well as cannabidiol or CBD. Finally, according to data demonstrating that aged astrocytes develop an A1 phenotype, we found that cholesterol buildup is also observed in reactive C3+ astrocytes. Given that reduced neuronal cholesterol affects synaptic plasticity, the ability of cannabinoids to restore cholesterol transport from aged astrocytes to neurons holds significant implications in aging and inflammation.

Assuntos

Transportador 1 de Cassete de Ligação de ATP , Astrócitos , Canabinoides , Colesterol , Lisossomos , Neurônios , Astrócitos/metabolismo , Astrócitos/efeitos dos fármacos , Animais , Colesterol/metabolismo , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Canabinoides/farmacologia , Canabinoides/metabolismo , Células Cultivadas , Proteína C1 de Niemann-Pick , Camundongos , Envelhecimento/metabolismo , Técnicas de Cocultura , Camundongos Endogâmicos C57BL

RESUMO

INTRODUCTION: Patients with psoriatic arthritis have some lipid metabolism changes and higher risk of metabolic syndrome (MetS) and cardiovascular diseases, regardless of traditional risk factors, suggesting that chronic inflammation itself plays a central role concerning the atherosclerosis. However, there is a lack of information regarding atherogenic pattern and lipoprotein subfractions burden in these individuals. AIM: To evaluate the HDL and LDL-cholesterol plasmatic levels and their subfractions after a nutritional intervention in patients with psoriatic arthritis (PsA). METHODS: This was a randomized, placebo-controlled clinical trial of a 12-week nutritional intervention. PsA patients were randomly assigned to 1-Placebo: 1 g of soybean oil daily, no dietetic intervention; 2-Diet + Supplementation: an individualized diet, supplemented with 604 mg of omega-3 fatty acids, three times a day; and 3-Diet + Placebo: individualized diet + 1 g of soybean oil. The LDL subfractions were classified as non-atherogenic (NAth), atherogenic (Ath) or highly atherogenic (HAth), whereas the HDL subfractions were classified as small, medium, or large particles, according to the current recommendation based on lipoproteins electrophoresis. RESULTS: A total of 91 patients were included in the study. About 62% of patients (n = 56) had an Ath or HAth profile and the main risk factors associated were male gender, longer skin disease duration and higher BMI. Thirty-two patients (35%) had a high-risk lipoprotein profile despite having LDL plasmatic levels below 100 mg/dL. The 12-week nutritional intervention did not alter the LDL subfractions. However, there were significant improvement of HDL subfractions. CONCLUSION: Recognizing the pro-atherogenic subfractions LDL pattern could be a relevant strategy for identifying PsA patients with higher cardiovascular risk, regardless total LDL plasmatic levels and disease activity. In addition, a short-term nutritional intervention based on supervised and individualized diet added to omega-3 fatty acids changed positively the HDLLARGE subfractions, while LDLLARGE subfraction was improved in hypercholesterolemic individuals. CLINICALTRIALS: gov identifier: NCT03142503 ( http://www. CLINICALTRIALS: gov/ ).

Assuntos

Artrite Psoriásica , HDL-Colesterol , LDL-Colesterol , Humanos , Artrite Psoriásica/dietoterapia , Artrite Psoriásica/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , LDL-Colesterol/sangue , HDL-Colesterol/sangue , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/uso terapêutico , Óleo de Soja/administração & dosagem , Aterosclerose/prevenção & controle , Aterosclerose/sangue

RESUMO

Cardiovascular disease (CVD) is the primary cause of death and disability worldwide. Although age-standardized CVD mortality rates decreased globally by 14.5% between 2006 and 2016, the burden of CVD remains disproportionately higher in low- and middle-income countries compared to high-income countries. Even though proven, effective approaches based on multiple-drug intake aimed at the prevention and treatment of CVD are currently available, poor adherence, early discontinuation of treatment, and suboptimal daily execution of the prescribed therapeutic regimes give rise to shortfalls in drug exposure, leading to high variability in the responses to the prescribed medications. Wald and Law, in their landmark paper published in BMJ 2003, hypothesized that the use of a fixed-dose combination of statins, ß-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and aspirin (classic Polypill composition) may increase adherence and decrease CVD by up to 80% when prescribed as primary prevention or in substitution of traditional protocols. Since then, many clinical trials have tested this hypothesis, with comparable results. This review aims to describe the available clinical trials performed to assess the impact of fixed-dose combinations on adherence, cost-effectiveness, and the risk factors critical to the onset of CVD.

RESUMO

Hypercholesterolemia is one of the most important risk factors for cardiovascular diseases. However, it is mostly associated with vascular dysfunction and atherosclerotic lesions, while evidence of direct effects of hypercholesterolemia on cardiomyocytes and heart function is still incomplete and controversial. In this study, we assessed the direct effects of hypercholesterolemia on heart function and the electro-contractile properties of isolated cardiomyocytes. After 5 weeks, male Swiss mice fed with AIN-93 diet added with 1.25% cholesterol (CHO), developed an increase in total serum cholesterol levels and cardiomyocytes cholesterol content. These changes led to altered electrocardiographic records, with a shortening of the QT interval. Isolated cardiomyocytes displayed a shortening of the action potential duration with increased rate of depolarization, which was explained by increased IK, reduced ICa.L and altered INa voltage-dependent inactivation. Also, reduced diastolic [Ca2+]i was found with preserved adrenergic response and cellular contraction function. However, contraction of isolated hearts is impaired in isolated CHO hearts, before and after ischemia/reperfusion, although CHO heart was less susceptible to arrhythmic contractions. Overall, our results demonstrate that early hypercholesterolemia-driven increase in cellular cholesterol content is associated with direct modulation of the heart and cardiomyocytes' excitability, Ca2+ handling, and contraction.

Assuntos

Hipercolesterolemia , Miócitos Cardíacos , Animais , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Hipercolesterolemia/fisiopatologia , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Camundongos , Masculino

RESUMO

INTRODUCTION: A new cardiovascular risk (CVR) calculator that incorporates Lipoprotein(a) [Lp(a)] levels has recently been designed. AIMS: To estimate CVR using the new score and to identify the reduction in low-density lipoprotein cholesterol (LDL-C) or systolic blood pressure (SBP) necessary to balance the risk attributable to Lp(a). METHODS: CVR throughout life and at 10 years was estimated with the new score in patients in primary prevention, both considering and not considering the value of Lp(a). When the estimated risk considering Lp(a) levels exceeded the baseline risk, the reduction in LDL-C levels or SBP necessary to balance the risk attributable to Lp(a) was calculated. RESULTS: In total, 671 patients (mean age 54.2 years, 47.2% women) were included. Globally, 22.7% of the population had high Lp(a) values (> 50 mg/dL or > 125 nmol/L). When calculating CVR throughout life and considering the Lp(a) value, the global risk increased in 66.7% of cases (median 19.3%). Similar results were observed when we assessed the 10-year risk. The risk associated with Lp(a) could be completely compensated by decreasing LDL-C (average 21 mg/dL) or SBP (average 6.3 mmHg) in 79.2% and 74.7% of cases, respectively. CONCLUSION: When calculating the CVR with the new score, two-thirds and one-third of the population were bidirectionally recategorized as 'up' or 'down,' respectively. The decrease in LDL-C or SBP mitigated the increased risk caused by Lp(a) levels across a substantial proportion of patients.

Assuntos

Biomarcadores , Pressão Sanguínea , Doenças Cardiovasculares , LDL-Colesterol , Fatores de Risco de Doenças Cardíacas , Lipoproteína(a) , Valor Preditivo dos Testes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/diagnóstico , LDL-Colesterol/sangue , Técnicas de Apoio para a Decisão , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Dislipidemias/tratamento farmacológico , Lipoproteína(a)/sangue , Prevenção Primária , Prognóstico , Medição de Risco , Fatores de Tempo

RESUMO

INTRODUCTION: Nutritional management plays a crucial role in treating patients with type 2 diabetes (T2D), working to prevent and control the progression of chronic non-communicable diseases. OBJECTIVES: To evaluate the effects of individualized nutritional interventions on weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides (TGs), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR)} over 12 months and subsequently at follow-up (15 months). METHODS: This longitudinal experimental study (without randomization and blinding) enrolled 84 sedentary participants with T2D (both sexes, aged 18-80 years). They were divided into a control group of 40 participants who received only medical consultations, and an intervention group of 44 participants who received the same medical care along with a nutritional assessment. Consultations occurred quarterly from August 2020 to November 2022 (first-twelfth month), with six to nine patients per session. Subsequently, a follow-up was conducted from December 2022 to November 2023, during which the intervention group had only medical care (during the 12th-15th months). Personalized dietary planning was inspired by the Mediterranean/DASH diets adapted to Brazilian foods and socioeconomic cultures. STATISTICAL ANALYSIS: Normal variables were compared between groups for each time point and also within each group across different time points using a two-way ANOVA (repeated measures for intragroup) followed by the Sídák post hoc test. Non-normal variables were compared between groups for each time point using Kruskal-Wallis followed by the Dunn post hoc test, and within each group across different time points using Friedman followed by the Dunn post hoc test. Data with a Gaussian distribution were presented as mean ± standard deviation (SD), and data with a non-Gaussian distribution were presented as median ± interquartile range (IQR). For all cases, α < 0.05 and p < 0.05 were adopted. RESULTS: In the intervention group, significant reductions were observed between the first and twelfth month for all parameters (p < 0.05), (except for TC), along with an increase in HDL-C (p = 0.0105). Conversely, in the control group, there was a significant increase in HbA1c, weight, BMI, FBG, and WHR (p < 0.05) between the first and twelfth months. Regarding the comparison between groups, there was a significant difference for all analyzed parameters (p < 0.05) from the first to the twelfth month. In the follow-up, differences were also observed (p < 0.05), except for BMI (p > 0.05). CONCLUSION: The individualized nutritional intervention improved eating habits, anthropometric, biochemical, and cardiovascular markers in T2D over 12 months, with sustained results during follow-up. The dietary plan inspired by the Mediterranean and DASH diets demonstrated good adaptation to the Brazilian food culture and the patients' socioeconomic contexts. Consistent monitoring and personalized nutritional management are essential for optimizing long-term outcomes. However, more clinical trials are necessary in order to optimize the level of evidence for longitudinal interventions.

Assuntos

Glicemia , Diabetes Mellitus Tipo 2 , Controle Glicêmico , Humanos , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Controle Glicêmico/métodos , Estudos Longitudinais , Glicemia/metabolismo , Fatores de Risco de Doenças Cardíacas , Hemoglobinas Glicadas/metabolismo , Doenças Cardiovasculares/prevenção & controle , Idoso de 80 Anos ou mais , Adulto Jovem , Índice de Massa Corporal , Adolescente , Pressão Sanguínea , Biomarcadores/sangue , Relação Cintura-Quadril , Circunferência da Cintura , Terapia Nutricional/métodos

RESUMO

High-density lipoprotein cholesterol (HDL-c) removes cholesterol, an essential component in lipid rafts, and this cholesterol removal can regulate protein attachment to lipid rafts, modulating their functionality in the immune cell response. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can alter the lipid profile, there is little information on the role of HDL-c and other lipids in prognostic of the coronavirus disease 2019 (COVID-19) in Mexican population. This study aims to evaluate the predictive value of HDL-c and lipid profile on severity and survival of 102 patients infected with SARS-CoV-2 during the COVID-19 first wave. Our findings, derived from univariate and multivariate Cox proportional hazards regression models, highlighted age and hypertension as significant predictors of survival (HR = 1.04, p = 0.012; HR = 2.78, p = 0.027), while gender, diabetes, and obesity showed no significant impact. Triglycerides and HDL-c levels notably influenced mortality, with elevated triglycerides and lower HDL-c associated with higher mortality risk (p = 0.032). This study underscores the importance of lipid profiles alongside traditional risk factors in assessing COVID-19 risk and outcomes. It contributes to the understanding of COVID-19 patient management and emphasizes the need for further investigation into the role of dyslipidemia in influencing COVID-19 prognosis, potentially aiding in refined risk stratification and therapeutic strategies.

Assuntos

COVID-19 , HDL-Colesterol , SARS-CoV-2 , Humanos , COVID-19/mortalidade , COVID-19/sangue , Masculino , Feminino , Pessoa de Meia-Idade , HDL-Colesterol/sangue , Adulto , Idoso , SARS-CoV-2/isolamento & purificação , Fatores de Risco , Triglicerídeos/sangue , Prognóstico , Lipídeos/sangue , México/epidemiologia , Dislipidemias/sangue , Modelos de Riscos Proporcionais , Hipertensão/sangue

RESUMO

OBJECTIVE: To evaluate the association between GGT/HDL-C ratio and resolution of MetS in adults after sleeve gastrectomy (SG). METHODS: We conducted a retrospective cohort study using secondary data from a Peruvian bariatric center. The study population consisted of adults aged 18 and above who underwent laparoscopic SG and were diagnosed with MetS prior to the surgery. The main outcome measured was MetS resolution 6 months post-surgery and the exposure variable was the GGT/HDL-C ratio. RESULTS: We analyzed 137 patients with a mean age of 38.9 ± 10.9 years; 64.2% were females. The median GGT/HDL-C ratio was 1.1 [0.7 - 1.5], and 83.9% of patients experienced resolution of MetS. Furthermore, both the middle tertile of GGT/HDL-C (aRR: 1.28; 95% CI: 1.04 - 1.58; p = .019) and the lowest tertile (aRR: 1.27; 95% CI: 1.01 - 1.60; p = .038) showed a significant association with the resolution of MetS. CONCLUSION: Eight out of 10 patients undergoing SG experience resolution of MetS within 6 months after surgery. Patients in the middle and lower tertiles of the GGT/HDL-C were more likely to achieve this outcome. Therefore, the GGT/HDL-C ratio should be considered a valuable and efficient biomarker for preoperative assessment of bariatric surgery candidates.

Assuntos

Biomarcadores , HDL-Colesterol , Gastrectomia , Síndrome Metabólica , gama-Glutamiltransferase , Humanos , Feminino , Adulto , Masculino , Estudos Retrospectivos , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Biomarcadores/sangue , HDL-Colesterol/sangue , Resultado do Tratamento , gama-Glutamiltransferase/sangue , Fatores de Tempo , Gastrectomia/efeitos adversos , Peru , Valor Preditivo dos Testes , Obesidade Mórbida/cirurgia , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Indução de Remissão , Redução de Peso , Laparoscopia/efeitos adversos , Fatores de Risco , Cirurgia Bariátrica/efeitos adversos

RESUMO

La alta prevalencia de hipotiroidismo subclínico en Chile puede deberse a que el límite superior normal de la hormona estimulante del tiroides (TSH) sérica es bajo. Personas con TSH levemente mayor al límite superior pueden ser metabólicamente similares a personas sanas. Se compararon marcadores de acción tiroidea (gasto energético en reposo [GER] y lipoproteína de baja densidad [LDL]) en adultos con hipotiroidismo subclínico leve y con función tiroidea normal con o sin tratamiento con levotiroxina. Se midió GER, perfil lipídico y tiroideo en personas sanas con función tiroidea normal (TSH ≥0,4-<4,5 µUI/ml; n=91); con hipotiroidismo subclínico leve (TSH ≥4,5-≤6,5 µUI/ml; n=5); y con hipotiroidismo clínico tratado con levotiroxina y TSH normal (n=13). Se analizó la LDL en 838 personas sanas con función tiroidea normal y 89 con hipotiroidismo subclínico leve de la Encuesta Nacional de Salud 2016/17 (ENS). El GER, ajustado por peso, sexo y edad, fue similar entre grupos (p=0,71). La LDL fue similar entre personas con función tiroidea normal e hipotiroidismo subclínico leve (91±24 vs. 101±17 mg/dl; p=0,67), y menor en hipotiroidismo tratado (64±22 mg/dl; p<0,01). La LDL no se asoció con TSH pero si inversamente con T4L en mujeres (r=-0,33; p=0,02; n=53). En la ENS, ambos grupos tuvieron similar LDL (p=0,34), la que se asoció inversamente con T4L en mujeres (r=-0,12; p=0,01; n=569) pero no con TSH. Personas sanas con función tiroidea normal y con hipotiroidismo subclínico leve tienen similar GER y LDL. Esto apoya la idea de redefinir el límite superior normal de TSH.

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The high prevalence of subclinical hypothyroidism in Chile may be due to the low normal upper limit of serum thyroid-stimulating hormone (TSH). People with TSH slightly higher than the upper limit may be metabolically similar to healthy people. Thyroid action markers (resting energy expenditure [REE] and low-density lipoprotein [LDL]) were compared in adults with mild subclinical hypothyroidism and with normal thyroid function with or without levothyroxine treatment. REE, lipid and thyroid profile were measured in healthy people with normal thyroid function (TSH ≥0,4-<4,5 µUI/ml (n=91); with mild subclinical hypothyroidism (TSH ≥4,5-≤6 µUI/ml; n=5); and with clinical hypothyroidism treated with levothyroxine and normal TSH (n=13). LDL was analyzed in 838 healthy people with normal thyroid function and 89 with mild subclinical hypothyroidism from the 2016/17 National Health Survey (NHS). REE, adjusted for weight, sex and age, was similar between the groups (p=0,71). LDL was similar between people with normal thyroid function and mild subclinical hypothyroidism (91±24 vs. 101±17 mg/dl; p=0,67), and lower in treated hypothyroidism (64±22 mg/dl; p<0,01). LDL was not associated with TSH but was inversely with FT4 in women (r=-0,33; p=0,02; n=53). In the NHS, both groups had similar serum LDL (p=0,34), which was inversely associated with FT4 in women (r=-0,12; p=0,01; n=569), but not with TSH. Healthy people with normal thyroid function and mild subclinical hypothyroidism have similar REE and LDL. These results support the idea of redefining the normal upper limit of TSH.