RESUMEN

BACKGROUND: Sepsis-induced cardiomyopathy (SICM) is common complication in septic patients with a high mortality and is characterized by an abnormal inflammation response, which was precisely regulated by endogenous specialized pro-resolving mediators (SPMs). However, the metabolic changes of cardiac SPMs during SICM and the roles of SPMs subset in the development of SICM remain unknown. METHODS: In this work, the SPMs concentration was assessed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) of SICM mice and SICM patients. The cardiac function was measured by echocardiography after the treatment of a SPMs subset, termed Resolvin D2 (RvD2). Caspase-11-/-, GSDMD-/- and double deficient (Caspase-11-/-GSDMD-/-) mice were used to clarify the mechanisms of RvD2 in SICM. RESULTS: We found that endogenous cardiac SPMs were disorders and RvD2 was decreased significantly and correlated with left ventricular ejection fraction (LVEF) and ß-BNP, cTnT in Lipopolysaccharide/Cecum ligation and puncture (CLP) induced SICM models. Treatment with RvD2 attenuated lethality, cardiac dysfunction and cardiomyocytes death during SICM. Mechanistically, RvD2 alleviated SICM via inhibiting Caspase-11/GSDMD-mediated cardiomyocytes pyroptosis. Finally, the plasma levels of RvD2 were also decreased and significantly correlated with IL-1ß, ß-BNP, cTnT and LVEF in patients with SICM. Of note, plasma RvD2 level is indicator of SICM patients from healthy controls or sepsis patients. CONCLUSION: These findings suggest that decreased cardiac RvD2 may involve in the pathogenesis of SICM. In addition, treatment with RvD2 represents a novel therapeutic strategy for SICM by inhibiting cardiomyocytes pyroptosis.

Asunto(s)

Cardiomiopatías , Ácidos Docosahexaenoicos , Sepsis , Humanos , Ratones , Animales , Piroptosis , Cromatografía Liquida , Volumen Sistólico , Espectrometría de Masas en Tándem , Función Ventricular Izquierda , Cardiomiopatías/etiología , Cardiomiopatías/genética , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/genética , Gasderminas , Proteínas de Unión a Fosfato/genética

RESUMEN

The lymphatic vasculature is the natural pathway for the resolution of inflammation, yet the role of pulmonary lymphatic drainage function in sepsis-induced acute respiratory distress syndrome (ARDS) remains poorly characterized. In this study, indocyanine green-near infrared lymphatic living imaging was performed to examine pulmonary lymphatic drainage function in septic mouse models. We found that the pulmonary lymphatic drainage was impaired owing to the damaged lymphatic structure in sepsis-induced ARDS. Moreover, prior lymphatic defects by blocking vascular endothelial growth factor receptor-3 (VEGFR-3) worsened sepsis-induced lymphatic dysfunction and inflammation. Posttreatment with vascular endothelial growth factor-C (Cys156Ser) (VEGF-C156S), a ligand of VEGFR-3, ameliorated lymphatic drainage by rejuvenating lymphatics to reduce the pulmonary edema and promote draining of pulmonary macrophages and neutrophils to pretracheal lymph nodes. Meanwhile, VEGF-C156S posttreatment reversed sepsis-inhibited CC chemokine ligand 21 (CCL21), which colocalizes with pulmonary lymphatic vessels. Furthermore, the advantages of VEGF-C156S on the drainage of inflammatory cells and edema fluid were abolished by blocking VEGFR-3 or CCL21. These results suggest that efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS. Our findings offer a therapeutic approach to sepsis-induced ARDS by promoting lymphatic drainage function.

Asunto(s)

Vasos Linfáticos , Síndrome de Dificultad Respiratoria , Sepsis , Ratones , Animales , Factor C de Crecimiento Endotelial Vascular/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ligandos , Vasos Linfáticos/patología , Inflamación/metabolismo , Síndrome de Dificultad Respiratoria/patología , Sepsis/metabolismo

RESUMEN

Physiological activity cannot be regulated without the blood and lymphatic vasculatures, which play complementary roles in maintaining the body's homeostasis and immune responses. Inflammation is the body's initial response to pathological injury and is responsible for protecting the body, removing damaged tissues, and restoring and maintaining homeostasis in the body. A growing number of researches have shown that blood and lymphatic vessels play an essential role in a variety of inflammatory diseases. In the inflammatory state, the permeability of blood vessels and lymphatic vessels is altered, and angiogenesis and lymphangiogenesis subsequently occur. The blood vascular and lymphatic vascular systems interact to determine the development or resolution of inflammation. In this review, we discuss the changes that occur in the blood vascular and lymphatic vascular systems of several organs during inflammation, describe the different scenarios of angiogenesis and lymphangiogenesis at different sites of inflammation, and demonstrate the prospect of targeting the blood vasculature and lymphatic vasculature systems to limit the development of inflammation and promote the resolution of inflammation in inflammatory diseases.

RESUMEN

Sepsis, a life-threatening organ dysfunction, is not caused by direct damage of pathogens and their toxins but by the host's severe immune and metabolic dysfunction caused by the damage when the host confronts infection. Previous views focused on the damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), including metabolic proinflammatory factors in sepsis. Recently, new concepts have been proposed to group free fatty acids (FFAs), glucose, advanced glycation end products (AGEs), cholesterol, mitochondrial DNA (mtDNA), oxidized phospholipids (OxPLs), ceramides, and uric acid into metabolism-associated molecular patterns (MAMPs). The concept of MAMPs will bring new guidance to the research and potential treatments of sepsis. Nowadays, sepsis is regarded as closely related to metabolic disorders, and MAMPs play an important role in the pathogenesis and development of sepsis. According to this view, we have explained MAMPs and their possible roles in the pathogenesis of sepsis. Next, we have further explained the specific functions of different types of MAMPs in the metabolic process and their interactional relationship with sepsis. Finally, the therapeutic prospects of MAMPs in sepsis have been summarized.

Asunto(s)

Sepsis , Alarminas , Humanos , Mitocondrias/metabolismo , Moléculas de Patrón Molecular Asociado a Patógenos

RESUMEN

ABSTRACT: Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by increased permeability of the alveolar-capillary barrier and impaired alveolar fluid clearance. Resolvin E1 (RvE1) is a specialized pro-resolving mediator derived endogenously from omega-3-polyunsaturated fatty acids. RvE1 (10 µg/kg i.v.) was injected to rats 6 h post-lipopolysaccharide (LPS) (14 mg/kg) induction. After another 3 h, alveolar fluid clearance was measured in live rats (n = 8-9). The primary Type II alveolar epithelial cell was isolated and treated by LPS (1 µg/mL) with or without RvE1 (250 nM). The expression of epithelial sodium channel (ENaC), Na+/K+-ATPase (NKA), AKT, serum- and glucocorticoid-induced kinase 1 (SGK1), and Nedd4-2 were detected. RvE1 improved survival rate (30% vs. 70%, P = 0.048), increased the clearance of alveolar fluid (13.34% vs. 18.73%, P  < 0.001), reduced lung wet-dry weight ratio (5.01 vs. 4.63, P  < 0.001), mitigated lung injury scores (13.38 vs. 7.0, P  < 0.05) and inflammation in LPS-induced ARDS in rats. RvE1 upregulated alveolar ENaC and NKA expression in vivo and in vitro. In addition, RvE1 significantly increased the expression of phosphorylated AKT, SGK1, and phosphorylated Nedd4-2 in LPS-stimulated primary alveolar type II cells. The effects of RvE1 were abrogated by blocking phosphatidylinositide3'-kinase (PI3K) and SGK1 with LY294002 and GSK650394, respectively. In summary, RvE1 upregulated ENaC and NKA expression by activating PI3K/AKT/SGK1 pathway to promote alveolar fluid clearance, suggesting that RvE1 may be a potentially effective drug for ARDS treatment.

Asunto(s)

Lesión Pulmonar Aguda , Síndrome de Dificultad Respiratoria , Lesión Pulmonar Aguda/metabolismo , Animales , Ácido Eicosapentaenoico/análogos & derivados , Canales Epiteliales de Sodio/metabolismo , Canales Epiteliales de Sodio/uso terapéutico , Lipopolisacáridos/toxicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , ATPasa Intercambiadora de Sodio-Potasio/efectos adversos , ATPasa Intercambiadora de Sodio-Potasio/metabolismo

RESUMEN

Acute respiratory distress syndrome (ARDS), a common and fatal clinical condition, is characterized by the destruction of epithelium and augmented permeability of the alveolar-capillary barrier. Resolvin conjugates in tissue regeneration 1 (RCTR1) is an endogenous lipid mediator derived from docosahexaenoic acid , exerting proresolution effects in the process of inflammation. In our research, we evaluated the role of RCTR1 in alveolar fluid clearance (AFC) in lipopolysaccharide-induced ARDS/acute lung injury (ALI) rat model. Rats were injected with RCTR1 (5 µg/kg) via caudal veins 8 hours after lipopolysaccharide (LPS) (14 mg/kg) treatment, and then AFC was estimated after 1 hour of ventilation. Primary type II alveolar epithelial cells were incubated with LPS (1 ug/ml) with or without RCTR1 (10 nM) for 8 hours. Our results showed that RCTR1 significantly enhanced the survival rate, promoted the AFC, and alleviated LPS-induced ARDS/ALI in vivo. Furthermore, RCTR1 remarkably elevated the protein expression of sodium channels and Na, K-ATPase and the activity of Na, K-ATPase in vivo and in vitro. Additionally, RCTR1 also decreased neural precursor cell expressed developmentally downregulated 4-2 (Nedd4-2) level via upregulating Ser473-phosphorylated-Akt expression. Besides this, inhibitors of receptor for lipoxin A4 (ALX), cAMP, and phosphatidylinositol 3-kinase (PI3K) (BOC-2, KH-7, and LY294002) notably inhibited the effects of RCTR1 on AFC. In summary, RCTR1 enhances the protein levels of sodium channels and Na, K-ATPase and the Na, K-ATPase activity to improve AFC in ALI through ALX/cAMP/PI3K/Nedd4-2 pathway, suggesting that RCTR1 may become a therapeutic drug for ARDS/ALI. SIGNIFICANCE STATEMENT: RCTR1, an endogenous lipid mediator, enhanced the rate of AFC to accelerate the resolution of inflammation in the LPS-induced murine lung injury model. RCTR1 upregulates the expression of epithelial sodium channels (ENaCs) and Na, K-ATPase in vivo and in vitro to accelerate the AFC. The efficacy of RCTR1 on the ENaC and Na, K-ATPase level was in an ALX/cAMP/PI3K/Nedd4-2-dependent manner.

Asunto(s)

Lesión Pulmonar Aguda/metabolismo , Ácidos Docosahexaenoicos/farmacología , Agonistas del Canal de Sodio Epitelial/farmacología , Canales Epiteliales de Sodio/metabolismo , Alveolos Pulmonares/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Animales , Ácidos Docosahexaenoicos/análogos & derivados , Ácidos Docosahexaenoicos/uso terapéutico , Lipopolisacáridos/toxicidad , Masculino , Alveolos Pulmonares/efectos de los fármacos , Ratas , Ratas Sprague-Dawley

RESUMEN

BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating clinical conditions characterized by pulmonary epithelial damage and protein-rich fluid accumulation in the alveolar spaces. Statins are a class of HMG-CoA reductase inhibitors, which exert cholesterol-lowering and anti-inflammatory effects. METHODS: Rosuvastatin (1 mg/kg) was injected intravenously in rats 12 h before lipopolysaccharide (LPS, 10 mg/kg) administration. Eight hours later after LPS challenge, alveolar fluid clearance (AFC) was detected in rats (n = 6-8). Rosuvastatin (0.3 µmol/mL) and LPS were cultured with primary rat alveolar type II epithelial cells for 8 h. RESULTS: Rosuvastatin obviously improved AFC and attenuated lung-tissue damage in ALI model. Moreover, it enhanced AFC by increasing sodium channel and Na,K-ATPase protein expression. It also up-regulated P-Akt via reducing Nedd4-2 in vivo and in vitro. Furthermore, LY294002 blocked the increase in AFC in response to rosuvastatin. Rosuvastatin-induced AFC was found to be partly rely on sodium channel and Na,K-ATPase expression via the PI3K/AKT/Nedd4-2 pathway. CONCLUSION: In summary, the findings of our study revealed the potential role of rosuvastatin in the management of ALI/ARDS.

RESUMEN

Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist, which can regulate inflammatory responses. However, whether DEX interferes with the inflammation resolving remains unclear. Here, we reported the effects of DEX on zymosan-induced generalized inflammation in mice during resolution. Mice were administered intraperitoneally with DEX after the initiation of sepsis. The resolution interval (Ri), a vital resolution indice, decreased from twelve hours to eight hours after the administration of DEX. The induction of peritoneal pro-inflammatory interleukin [IL] - 1ß and tumour necrosis factor-α (TNF-α) appeared to be inhibited. Of interest, the anti-inflammatory transforming growth factor-ß1 (TGF-ß1) but not IL-10 levels were up-regulated at twenty-four hours in the DEX group along with 1.0 mg/mice zymosan A (ZyA) treatment. The expression levels of multiple genes related to protective immune processes and clearance functions were detected and revealed the same trends. DEX markedly increased the F4/80+Ly6G+ macrophage population. Additionally, the adequate apoptotic neutrophil clearance from injury after DEX installation could be reverse by opsonization or co-instillation of TGF-ß1 neutralizing antibody in vivo, promoting the inflammation-resolution programs. In conclusion, DEX post-treatment, via the increase of F4/80+Ly6G+ macrophages, provokes further secretion of TGF-ß1, leading to the attenuated cytokine storm and accelerated inflammation resolving.

Asunto(s)

Antiinflamatorios/uso terapéutico , Dexmedetomidina/uso terapéutico , Macrófagos/efectos de los fármacos , Peritonitis/tratamiento farmacológico , Factor de Crecimiento Transformador beta1/inmunología , Animales , Antiinflamatorios/farmacología , Antígenos de Diferenciación/inmunología , Antígenos Ly/inmunología , Citocinas/genética , Citocinas/inmunología , Dexmedetomidina/farmacología , Macrófagos/inmunología , Masculino , Ratones Endogámicos C57BL , Peritonitis/genética , Peritonitis/inmunología , Factor de Crecimiento Transformador beta1/genética

RESUMEN

Acute respiratory distress syndrome (ARDS) is a lethal clinical syndrome characterized by damage of the epithelial barriers and accumulation of pulmonary edema fluid. Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenously produced lipid mediator, are believed to exert anti-inflammatory and pro-resolution effects. PCTR1 (1 µg/kg) was injected at 8 hr after lipopolysaccharide (LPS; 14 mg/kg) administration, and the rate of pulmonary fluid clearance was measured in live rats at 1 hr after PCTR1 treatment. The primary type II alveolar epithelial cells were cultured with PCTR1 (10 nmol/ml) and LPS (1 µg/ml) for 8 hr. PCTR1 effectively improved pulmonary fluid clearance and ameliorated morphological damage and reduced inflammation of lung tissue, as well as improved the survival rate in the LPS-induced acute lung injury (ALI) model. Moreover, PCTR1 markedly increased sodium channel expression as well as Na, K-ATPase expression and activity in vivo and in vitro. In addition, PCTR1i also upregulated the expression of LYVE-1 in vivo. Besides that, BOC-2, HK7, and LY294002 blocked the promoted effect of PCTR1 on pulmonary fluid clearance. Taken together, PCTR1 upregulates sodium channels' expression via activating the ALX/cAMP/P-Akt/Nedd4-2 pathway and increases Na, K-ATPase expression and activity to promote alveolar fluid clearance. Moreover, PCTR1 also promotes the expression of LYVE-1 to recover the lymphatic drainage resulting in the increase of lung interstitial fluid clearance. In summary, these results highlight a novel systematic mechanism for PCTR1 in pulmonary edema fluid clearance after ALI/ARDS, suggesting its potential role in a therapeutic approach for ALI/ARDS.

Asunto(s)

Lesión Pulmonar Aguda/tratamiento farmacológico , Antígenos CD59/farmacología , Canales Epiteliales de Sodio/genética , Edema Pulmonar/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/patología , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/patología , Animales , Antiinflamatorios/farmacología , Líquidos Corporales/efectos de los fármacos , Antígenos CD59/química , Antígenos CD59/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/química , Ácidos Docosahexaenoicos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Lipopolisacáridos/toxicidad , Pulmón/efectos de los fármacos , Pulmón/patología , Fosfatidilinositol 3-Quinasas/genética , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/patología , Edema Pulmonar/inducido químicamente , Edema Pulmonar/patología , Ratas , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/genética , Transducción de Señal/efectos de los fármacos , ATPasa Intercambiadora de Sodio-Potasio/genética

RESUMEN

Gram-negative bacterial infection causes an excessive inflammatory response and acute organ damage or dysfunction due to its outer membrane component, lipopolysaccharide (LPS). Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenous lipid mediator, exerts fundamental anti-inflammation and pro-resolution during infection. In the present study, we examined the properties of PCTR1 on the systemic inflammatory response, organic morphological damage and dysfunction, and serum metabolic biomarkers in an LPS-induced acute inflammatory mouse model. The results show that PCTR1 reduced serum inflammatory factors and ameliorated morphological damage and dysfunction of the lung, liver, kidney, and ultimately improved the survival rate of LPS-induced acute inflammation in mice. In addition, metabolomics analysis and high performance liquid chromatography-mass spectrometry revealed that LPS-stimulated serum linoleic acid (LA), arachidonic acid (AA), and prostaglandin E2 (PGE2) levels were significantly altered by PCTR1. Moreover, PCTR1 upregulated LPS-inhibited fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongase of very long chain fatty acids 2 (ELOVL2) expression, and downregulated LPS-stimulated phospholipase A2 (PLA2) expression to increase the intrahepatic content of AA. However, these effects of PCTR1 were partially abrogated by a lipoxin A4 receptor (ALX) antagonist (BOC-2). In summary, via the activation of ALX, PCTR1 promotes the conversion of LA to AA through upregulation of FADS1, FADS2, and ELOVL2 expression, and inhibits the conversion of bound AA into free AA through downregulation of PLA2 expression to decrease the serum AA and PGE2 levels.

Asunto(s)

Ácidos Docosahexaenoicos/farmacología , Inflamación/metabolismo , Ácido Linoleico/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Fosfolipasas A2/metabolismo , Animales , Antígenos CD59 , Ácidos Docosahexaenoicos/química , Ácido Graso Desaturasas/genética , Ácido Graso Desaturasas/metabolismo , Elongasas de Ácidos Grasos/genética , Elongasas de Ácidos Grasos/metabolismo , Femenino , Inflamación/inducido químicamente , Lipopolisacáridos/efectos adversos , Masculino , Ratones , Ratones Endogámicos C57BL , Fosfolipasas A2/genética

RESUMEN

Maresin Conjugates in Tissue Regeneration 1 (MCTR1) is a newly identified macrophage-derived sulfido-conjugated mediator that stimulates the resolution of inflammation. This study assessed the role of MCTR1 in alveolar fluid clearance (AFC) in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Rats were intravenously injected with MCTR1 at a dose of 200 ng/rat, 8 hours after administration of 14 mg/kg LPS. The level of AFC was then determined in live rats. Primary rat ATII (Alveolar Type II) epithelial cells were also treated with MCTR1 (100 nmol/L) in a culture medium containing LPS for 8 hours. MCTR1 treatment improved AFC (18.85 ± 2.07 vs 10.11 ± 1.08, P < .0001) and ameliorated ALI in rats. MCTR1 also significantly promoted AFC by up-regulating epithelial sodium channel (ENaC) and Na+ -K+ -adenosine triphosphatase (Na, K-ATPase) expressions in vivo. MCTR1 also activated Na, K-ATPase and elevated phosphorylated-Akt (P-Akt) by up-regulating the expression of phosphorylated Nedd4-2 (P-Nedd4-2) in vivo and in vitro. However, BOC-2 (ALX inhibitor), KH7 (cAMP inhibitor) and LY294002 (PI3K inhibitor) abrogated the improved AFC induced by MCTR1. Based on the findings of this study, MCTR1 may be a novel therapeutic approach to improve reabsorption of pulmonary oedema during ALI/acute respiratory distress syndrome (ARDS).

Asunto(s)

Lesión Pulmonar Aguda/terapia , Células Epiteliales Alveolares/efectos de los fármacos , Proteínas de Ciclo Celular/farmacología , Proteínas Oncogénicas/farmacología , Alveolos Pulmonares/efectos de los fármacos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/genética , Células Epiteliales Alveolares/metabolismo , Animales , Proteínas de Ciclo Celular/genética , Canales Epiteliales de Sodio/genética , Regulación de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/toxicidad , Proteínas Oncogénicas/genética , Fosfatidilinositol 3-Quinasas/genética , Fosforilación , Alveolos Pulmonares/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , ATPasa Intercambiadora de Sodio-Potasio/genética

RESUMEN

INTRODUCTION: This study evaluates an insulin dose titration model and factors that impact insulin dose adjustment in Chinese adults with type-2 diabetes, who receive basal insulin in real-world settings. MATERIAL AND METHODS: A total of 19,894 patients from the ORBIT study were included. These patients were divided into four groups, according to the type of insulin dose adjustment: no insulin titration (group A), self-titration (group B), physician-led insulin titration (group C), and combined physician and patient-led insulin titration (group D). Data were collected and compared at baseline and after six months of treatment. RESULTS: A total of 12,865 patients completed the visits and were included in the analysis. Among these patients, 3187 (24.8%), 1971 (15.3%), 5165 (40.1%), and 2542 (19.8%) patients were included in groups A, B, C, and D, respectively. The multivariate logistic regression analysis revealed that the duration of diabetes, body mass index, microvascular complications, inpatient days, HbA1C level, and self-monitoring of blood glucose (SMBG) were positively correlated with insulin titration in group B, C, and D, compared with group A. The number of inpatient days and outpatient visits were positively correlated with dose adjustment for physician-led titration, while this was negatively correlated for self-titration. Self-titration encouraged by physicians and home blood glucose monitoring were positively correlated with self-titration and the combined physician and patient-led titration. CONCLUSIONS: High HbA1C level, SMBG, long disease duration, microvascular complications, and the encouragement of physicians while initiating insulin use prompt patients to perform dose adjustments in real-world settings.

Asunto(s)

Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina/uso terapéutico , Anciano , Pueblo Asiatico , Automonitorización de la Glucosa Sanguínea , China , Diabetes Mellitus Tipo 2/sangre , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros

RESUMEN

BACKGROUND: Apolipoprotein M (apoM) was the carrier of the biologically active lipid mediator sphingosine-1-phospate in high density lipoprotein cholesterol (HDL-C) and played a critical role in formation and maturation of prebeta-HDL-C particles. The plasma apoM levels were decreased obviously in patients with type 2 diabetes mellitus (T2DM). A new single-nucleotide polymorphism (SNP) C-724del in apoM promoter was associated with a higher risk for coronary artery diseases (CAD) and myocardial infarction, could reduce promoter activities and apoM expression in vitro. The primary aim of the present case-controls study was to investigate the effect of apoM SNP C-724del on apoM expression in vivo and its association with T2DM susceptibility in an eastern Han Chinese cohort. METHODS: Two hundred and fifty-nine T2DM patients and seventy-six healthy controls were included in this study. Amplifying DNA of apoM proximal promoter region including SNP C-724del by Real-Time Polymerase Chain Reaction (RT-PCR) and amplicons sequencing. The plasma apoM concentrations were assayed by enzyme linked immunosorbentassay (ELISA). RESULTS: Four polymorphic sites, rs805297 (C-1065A), rs9404941 (T-855C), rs805296 (T-778C), C-724del were confirmed. rs805297 (C-1065A) and rs9404941 (T-855C) showed no statistical difference in allele frequencies and genotype distributions between T2DM patients and healthy controls just as previous studies. It's worth noting that the difference of rs805296 (T-778C) between these two groups was not found in this study. In SNP C-724del, the frequency of del allele and mutant genotypes (del/del, C/del) were higher in T2DM patients compared with healthy controls (p = 0.035; P = 0.040, respectively), while the plasma apoM levels of C-724del mutant allele carriers compared with the wide-type homozygotes carriers were not statistically different in T2DM patients (18.20 ± 8.53 ng/uL vs 20.44 ± 10.21 ng/uL, P = 0.245). CONCLUSION: The polymorphism C-724del in the promoter region of the apoM gene could confer the risk of T2DM among eastern Han Chinese. Unfortunately, the lowing of plasma apoM levels of C-724del mutant allele carriers compared with the wide-type homozygotes carriers in T2DM patients was not statistically different in present study, so further researchs were needed by enlarging the sample.

Asunto(s)

Apolipoproteínas/genética , Diabetes Mellitus Tipo 2/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Lipocalinas/genética , Adulto , Anciano , Apolipoproteínas/sangre , Apolipoproteínas M , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/patología , Femenino , Genotipo , Humanos , Lipocalinas/sangre , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Riesgo , Eliminación de Secuencia

RESUMEN

BACKGROUND AND OBJECTIVE: It is necessary to develop an effective and low-cost screening tool for identifying Chinese people at high risk of stroke. Transcranial Doppler ultrasound (TCD) is a powerful predictor of stroke in the pediatric sickle cell disease population, as demonstrated in the STOP trial. Our study was conducted to determine the prediction value of peak systolic velocities as measured by TCD on subsequent stroke risk in a prospective cohort of the general population from Beijing, China. METHODS: In 2002, a prospective cohort study was conducted among 1392 residents from 11 villages of the Shijingshan district of Beijing, China. The cohort was scheduled for follow up with regard to incident stroke in 2005, 2007, and 2012 by a study team comprised of epidemiologists, nurses, and physicians. Univariate and multivariate Cox proportional hazard regression models were used to determine the factors associated with incident stroke. RESULTS: Participants identified by TCD criteria as having intracranial stenosis had a 3.6-fold greater risk of incident stroke (hazard ratio (HR) 3.57, 95% confidence interval (CI) 1.86-6.83, P<0.01) than those without TCD evidence of intracranial stenosis. The association remained significant in multivariate analysis (HR 2.53, 95% CI 1.31-4.87) after adjusting for other risk factors or confounders. Older age, cigarette smoking, hypertension, and diabetes mellitus remained statistically significant as risk factors after controlling for other factors. CONCLUSIONS: The study confirmed the screening value of TCD among the general population in urban China. Increasing the availability of TCD screening may help identify subjects as higher risk for stroke.

Asunto(s)

Circulación Cerebrovascular , Accidente Cerebrovascular/diagnóstico , Ultrasonografía Doppler Transcraneal , Anciano , Velocidad del Flujo Sanguíneo , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/patología , Análisis de Supervivencia , Sístole

RESUMEN

Apolipoprotein M (ApoM) is a novel lipoprotein-associated plasma protein of the apolipoprotein family. It is predominantly enriched in high-density lipoprotein (HDL), and is also present in small quantities in low-density lipoprotein (LDL) and in very low-density lipoprotein. Transgenic animal experiments have suggested that ApoM can be transformed into various lipoproteins and may be involved in lipoprotein metabolism. ApoM has five subtypes, however, their biological functions remain to be elucidated. The α-helix, formed by ApoM through hydrophobic signal peptides, is anchored to the phospholipid monomolecular layers of HDL. Hydrophobic domains can associate with small lipophilic ligands and perform biological functions. ApoM may affect HDL metabolism and exhibit anti-atherosclerotic functions. Human HDL, containing ApoM subfractions, can protect LDL from oxidation and regulate cholesterol efflux more effectively than HDL without ApoM. Therefore, it is highly correlated with plasma cholesterol levels in the human body. Although previous studies have reported no difference in ApoM between groups of patients with coronary heart disease (CHD) and a normal control groups, the anti-atherosclerotic effect of ApoM is evident. ApoM is highly expressed in renal proximal tubule cells and is secreted into the urine in tubule cells. However, it is usually reabsorbed by giantin-associated proteins in a process, which is also affected in kidney disease. In addition to liver and kidney cells, low expression levels of ApoM occur in the intestinal tract and are associated with lymph node metastasis of colorectal cancer. ApoM gene polymorphism is associated with CHD, diabetes and other immune-associated diseases. Investigations into the gene regulation of ApoM may assist in further clarifying the role of ApoM in blood glucose and lipid metabolism. Genetic modification of the mouse ApoM gene is an essential technique to investigate the gene expression and regulation of ApoM, and to clarify the potential roles of ApoM in lipoprotein metabolism, atherosclerosis, diabetes and renal diseases.

Asunto(s)

Apolipoproteínas/metabolismo , Lipocalinas/metabolismo , Lipoproteínas/metabolismo , Animales , Apolipoproteínas/química , Apolipoproteínas/genética , Apolipoproteínas M , Enfermedad Coronaria/genética , Enfermedad Coronaria/patología , Diabetes Mellitus/genética , Diabetes Mellitus/patología , Humanos , Lipocalinas/química , Lipocalinas/genética , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Hígado/metabolismo

RESUMEN

BACKGROUND: Since men with chronic kidney disease (CKD) progress faster than women, an accurate assessment of CKD progression rates should be based on gender differences in age-related decline of glomerular filtration rate (GFR) in healthy individuals. METHODS: A Chinese sample population from a stratified, multistage, and clustered CKD screening study was classified into healthy, at-risk, and CKD groups. The gender differences in estimated GFR (eGFR) and age-related eGFR decline were calculated for each group after controlling for blood pressure, fasting glucose levels, serum lipids levels, education level, and smoking status. After referencing to the healthy group, gender-specific multivariate-adjusted rates of decline in eGFR and differences in the rates of decline were calculated for both CKD and at-risk groups. RESULTS: The healthy, at-risk, and CKD groups consisted of 4569, 7434, and 1573 people, respectively. In all the 3 groups, the multivariate-adjusted eGFRs in men were lower than the corresponding eGFRs in women. In addition, in the healthy and at-risk groups, the rates of decline in eGFR in men were lower than the corresponding rates of decline in women (healthy group: 0.51 mLxmin-1x1.73 m-2·yr-1 vs. 0.74 mLxmin-1x1.73 m-2xyr-1 and at-risk group: 0.60 mLxmin-1x1.73 m-2xyr-1 vs. 0.73 mLxmin-1x1.73 m-2xyr-1). However, in the CKD group, the rates of decline in eGFR in men were similar to those in women (0.96 mLxmin-1x1.73 m-2xyr-1 vs. 0.91 mLxmin-1x1.73 m-2xyr-1). However, after referencing to the healthy group, the rates of decline in eGFR in men in the at-risk and CKD groups were greater faster than the corresponding rates in women (at-risk group: 0.10 mLxmin-1x1.73 m-2·yr-1 vs. -0.03 mLxmin-1x1.73 m-2xyr-1 and CKD group: 0.44 mLxmin-1x1.73 m-2·yr-1 vs. 0.15 mLxmin-1x1.73 m-2xyr-1). CONCLUSION: To accurately assess gender differences in CKD progression rates, gender differences in age-related decline in GFR should be considered.

Asunto(s)

Envejecimiento/fisiología , Tasa de Filtración Glomerular , Enfermedades Renales/fisiopatología , Riñón/crecimiento & desarrollo , Caracteres Sexuales , Adulto , Anciano , China/epidemiología , Enfermedad Crónica , Comorbilidad , Progresión de la Enfermedad , Femenino , Humanos , Riñón/fisiopatología , Enfermedades Renales/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Muestreo , Factores Socioeconómicos , Adulto Joven

RESUMEN

To investigate combination patterns of cardiovascular risks and sequelae at different stages of hypertension, all 6176 newly or previously diagnosed hypertensives were selected from a randomized sampling surveillance data to perform a multiple correspondence analysis. Short duration hypertensives are characterized by relatively young age, less physical exercise, normal fruits and vegetable intakes, high salt diet, and nearly normal blood lipid and glucose. Middle duration hypertensives begin to pursue more physical exercise and less salt, although increasing physiological disorders are found. Severe sequelae such as stroke and myocardial infraction mainly occurred in long duration hypertensives. Results imply that great efforts should be taken in health education and lifestyle interventions on prehypertensive and early stage hypertensive patients.

Asunto(s)

Hipertensión/complicaciones , Hipertensión/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , China/epidemiología , Estudios Transversales , Ejercicio Físico , Femenino , Promoción de la Salud , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Prevalencia , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Encuestas y Cuestionarios

RESUMEN

OBJECTIVE: To evaluate the therapeutic effects of stem cell transplantation in heart failure patients with old myocardial infarction (OMI) by MRI. METHODS: Heart failure patients [NYHA 2.7 +/- 0.7, male = 18, mean age (59.5 +/- 10.1) y] with OMI were randomly divided into 2 groups (group A: CABG + stem cell transplantation, group B: CABG; n = 10 each). Left ventricular (LV) function was measured by MRI, viable myocardium was detected by (18)F-FDG myocardial metabolism imaging and late contrast-enhanced at baseline and 6 months post intervention. RESULTS: LVEF and LVEDV at baseline for group A were (20.71 +/- 6.09)% and (172.73 +/- 32.74) ml, and for group B were (27.59 +/- 2.31)% and (155.13 +/- 28.36) ml, respectively (P > 0.05). The LVEF was equally improved in group A and B (mean 8.63% vs. 10.37%, P > 0.05) while DeltaLVEDV was significant higher in group A than that in group B [(9.91 +/- 39.50) ml vs. (-22.34 +/- 31.35) ml, P < 0.05]. Ventricular wall thickening ratio at 6 months post intervention was significantly higher in group A than that in group B [(11.40 +/- 11.53)% vs. (2.27 +/- 7.20)%, P < 0.05]. Late contrast-enhanced MRI results correlated with (18)F-FDG myocardial metabolism imaging SPECT well in assessment of myocardial viability (kappa value: 0.446, P < 0.001; sensitivity: 68.3% and specificity: 92.5%). CONCLUSIONS: Stem cell therapy on top of CABG aggravated LV remodeling in heart failure patients with old myocardial infarction. The specificity of MRI is similar to (18)F-FDG SPECT while the sensitivity is inferior to (18)F-FDG SPECT on detecting viable myocardium.

Asunto(s)

Insuficiencia Cardíaca/terapia , Imagen por Resonancia Magnética , Infarto del Miocardio/terapia , Trasplante de Células Madre , Adulto , Anciano , Método Doble Ciego , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Sensibilidad y Especificidad , Resultado del Tratamiento , Remodelación Ventricular

Asunto(s)

Dislipidemias/epidemiología , Locomoción , Adulto , China/epidemiología , Femenino , Humanos , Incidencia , Estilo de Vida , Modelos Logísticos , Masculino , Transportes

RESUMEN

OBJECTIVE: To understand the prevalence and control of several common chronic disease in Beijing adults. METHODS: 16,658 adult residents were randomly selected with stratified multi-stage cluster sampling method. Each participant was invited to receive a set of standardized questionnaire, physical examinations and laboratory tests. RESULTS: Data showed that the prevalence, awareness, treatment and the rate of control on hypertension among the adults in Beijing were 29.1%, 49.3%, 42.3% and 10.6% respectively. The counterparts of diabetes mellitus were 8.8%, 56.7%, 50.0% and 15.0%. The four corresponding figures for dyslipidemia were 33.2%, 31.1%, 13.0% and 4.3%, respectively. 22.9% of the Beijing adults had metabolic syndrome including 8.1 per thousand suffering from myocardial infarction and 18.4 per thousand from stroke. Except for diabetes, all the chronic diseases had higher prevalence rate in rural area than in urban area, according to the findings under our study. Postmenopausal women were more susceptible to chronic disease than men. CONCLUSION: The prevalence rate of chronic disease in Beijing was still high. The prevalence rate in rural area had exceeded the level in urban area. Adjustment and attention should be made according to the prevalence features and weakness existed in present chronic disease control strategy.

Asunto(s)

Enfermedad Crónica/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Prevalencia , Adulto Joven