RESUMEN
Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs) in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to "endothelial progenitor cells" and "endothelium" and, for the different categories, respectively, "smoking"; "blood pressure"; "diabetes mellitus" or "insulin resistance"; "dyslipidemia"; "aging" or "elderly"; "angina pectoris" or "myocardial infarction"; "stroke" or "cerebrovascular disease"; "homocysteine"; "C-reactive protein"; "vitamin D". Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.
RESUMEN
BACKGROUND AND AIMS: Suboptimal vitamin D status was recently acknowledged as an independent predictor of cardiovascular diseases and all-cause mortality in several clinical settings, and its serum levels are commonly reduced in Rheumatoid Arthritis (RA). Patients affected by RA present accelerated atherosclerosis and increased cardiovascular morbidity and mortality with respect to the general population. In RA, it has been reported an impairment of the number and the activity of circulating proangiogenic haematopoietic cells (PHCs), including CD34+, that may play a role in endothelial homeostasis. The purpose of the study is to investigate the association between vitamin D levels and PHCs, inflammatory markers, and arterial stiffening in patients with RA. METHODS AND RESULTS: CD34+ cells were isolated from 27 RA patients and 41 controls. Vitamin D levels, C-reactive protein (CRP), fibrinogen, pulse wave velocity (PWV), and carotid intima-media thickness (cIMT) were also evaluated. CD34+ count and vitamin D levels were lower in RA patients as compared to controls, while fibrinogen, CRP, PWV and cIMT were higher in RA patients. CD34+ cell number appeared to be associated with vitamin D levels, and negatively correlated to fibrinogen and early atherosclerosis markers (PWV and cIMT); vitamin D levels appear also to be inversely associated to fibrinogen. CONCLUSIONS: RA patients with moderate disease activity presented with low vitamin D levels, low CD34+ cell count, increased PWV and cIMT; we found that vitamin D deficiency is associated to CD34+ cell reduction in peripheral blood, and with fibrinogen levels. This suggests that vitamin D might contribute to endothelial homeostasis in patients with RA.
Asunto(s)
Artritis Reumatoide/sangre , Aterosclerosis/sangre , Inflamación/sangre , Células Madre , Rigidez Vascular/fisiología , Deficiencia de Vitamina D/sangre , Vitamina D/sangre , Adulto , Artritis Reumatoide/complicaciones , Artritis Reumatoide/fisiopatología , Aterosclerosis/complicaciones , Aterosclerosis/fisiopatología , Proteína C-Reactiva , Grosor Intima-Media Carotídeo , Recuento de Células , Femenino , Fibrinógeno , Humanos , Inflamación/complicaciones , Inflamación/fisiopatología , Masculino , Persona de Mediana Edad , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/fisiopatologíaRESUMEN
HYPOTHESIS/INTRODUCTION: The aim of this study was to assess the antihypertensive efficacy and safety of aliskiren versus ramipril or losartan in hypertensive patients with type 2 diabetes mellitus, microalbuminuria and uncontrolled hypertension, despite the use of optimal conventional antihypertensive therapy. MATERIALS AND METHODS: In this open-label active comparator study, 126 patients were randomly assigned to receive 24 weeks of additional therapy with aliskiren (Group A) or either losartan or ramipril (Group B), according to whether a patient was already treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, respectively. RESULTS: After 24 weeks, both treatment groups experienced a significant reduction of systolic blood pressure (-11.37% and -8.47%, respectively; both p <0.001 vs. baseline) and diastolic blood pressure levels (-10.67% and -9.28%, respectively; both p <0.001 vs. baseline), with a greater reduction of mean systolic values in Group A compared with Group B (p <0.001). Furthermore, after six months microalbuminuria was significantly decreased in both treatment groups (-67.62% and -49.1%, respectively; both p <0.001), with a reduction rate in Group A significantly higher than in Group B (p<0.001). CONCLUSIONS: The addition of aliskiren to optimal conventional therapy provided a higher reduction of blood pressure and urinary albumin excretion when compared with the addition of losartan or ramipril.
Asunto(s)
Albuminuria/tratamiento farmacológico , Amidas/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fumaratos/uso terapéutico , Hipertensión/tratamiento farmacológico , Losartán/uso terapéutico , Ramipril/uso terapéutico , Anciano , Albuminuria/sangre , Albuminuria/complicaciones , Presión Sanguínea/efectos de los fármacos , Creatinina/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diástole/efectos de los fármacos , Quimioterapia Combinada , Femenino , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Potasio/sangre , Sístole/efectos de los fármacosRESUMEN
OBJECTIVES: Circulating proangiogenic haematopoietic cells (PHCs), including CD34+ cells, play an important role in endothelial homeostasis. Among PHCs, CD34+ cells are the largest cell population, thus, much of the regenerative/reparative potential of PHCs may be attributed to CD34+ cells. Our aim was to determine the association between inflammation and CD34+ cell number, intracellular levels of reactive oxygen species (ROS) and expression of Toll-like receptor 3 (TLR3) and interleukin 1ß (IL-1ß), arterial stiffness (AS) indices, and carotid intima-media thickness (cIMT) in patients affected by rheumatoid arthritis (RA). METHODS: CD34+ cells were isolated from 24 RA patients and 26 matched controls. ROS levels, TLR3 and IL-1ß expression were measured. C-reactive protein (CRP), fibrinogen, AS, and cIMT were also evaluated. RESULTS: CD34+ count was lower in RA patients as compared to controls. In CD34+ cells from RA patients, ROS, TLR3 and IL-1ß expressions were increased compared to controls. In RA patients, we found higher CRP and fibrinogen levels, and higher values of Pulse Wave Velocity (PWV) and Augmentation Index (AIx), both AS indices, and of cIMT. CD34+ cell numbers were inversely correlated with CRP, TLR3, IL-1ß, ROS, and AS indices. TLR3 levels were related to CRP, IL-1ß, fibrinogen and ROS. IL-1ß levels were correlated with expression of CRP, ROS, and PWV. CONCLUSIONS: Inflammatory status in RA is associated with an increased expression of TLR3 and of IL-1ß in CD34+ cells, which appear to affect cell number. These new findings suggest a perspective on accelerated atherosclerosis and vascular damage in RA.
Asunto(s)
Antígenos CD34/metabolismo , Artritis Reumatoide/metabolismo , Aterosclerosis/metabolismo , Células Endoteliales/metabolismo , Células Madre Hematopoyéticas/metabolismo , Mediadores de Inflamación/metabolismo , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Receptor Toll-Like 3/metabolismo , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Aterosclerosis/inmunología , Biomarcadores/metabolismo , Proteína C-Reactiva/metabolismo , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Estudios Transversales , Células Endoteliales/inmunología , Femenino , Células Madre Hematopoyéticas/inmunología , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Inflamación/inmunología , Masculino , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismo , Factores de Riesgo , Regulación hacia Arriba , Rigidez VascularRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and is associated with familial combined hyperlipidaemia (FCHL). Currently, the invasive liver biopsy is considered as the gold standard for evaluating liver fibrosis (LF); however, liver stiffness measurement (LSM) by transient elastography (TE) trough FibroScan device may be employed to estimate LF noninvasively. The aim of this study was to evaluate the prevalence of NAFLD in FCHL subjects and to analyse LSM with TE to better identify those individuals with a potential risk of liver disease progression. MATERIALS AND METHODS: Sixty subjects with FCHL (38 men, 22 women, mean age 46.4 +/- 10.9 years) were included in the study. We studied biochemical parameters including lipid profile, glucose, transaminase and insulin; blood pressure and waist circumference (WC) were measured; BMI and HOMA-index were calculated. Ultrasonography was performed to assess liver steatosis and carotid intima-media thickness (IMT). Liver fibrosis was measured by FibroScan. RESULTS: Patients were classified according to have no (group 0: 19%), mild (group 1: 32%) or moderate-severe (group 2: 49%) steatosis. No difference was found between group 0 and 1 concerning all study parameters. WC (P < 0.05), BMI (P < 0.05), glucose (P < 0.05), insulin (P < 0.001), HOMA-index (P < 0.001) and LSM (6.03 +/- 1.9 Kpa vs. 4.2 +/- 0.5 Kpa, P < 0.001) were significantly higher in group 2 than groups 1 and 0. Furthermore, LSM correlated with insulin (P < 0.05), glucose (P < 0.05), HOMA-index (P < 0.001), transaminase (P < 0.01) and liver steatosis (P < 0.001). Regression analysis showed that LSM (P < 0.001) and NAFLD (P < 0.01) is associated with HOMA-index; NAFLD is also associated with WC (P < 0.05). CONCLUSION: Our results suggest that in FCHL subjects, HOMA-index, an insulin resistance index, is strongly associated with liver steatosis and its progression. Furthermore, in these subjects, we propose the transient elastography to identify and follow up patients for the progression of hepatic disease.
Asunto(s)
Hígado Graso/epidemiología , Hígado Graso/patología , Hiperlipidemia Familiar Combinada/complicaciones , Cirrosis Hepática/diagnóstico , Hígado/patología , Adulto , Arterias Carótidas/patología , Progresión de la Enfermedad , Diagnóstico por Imagen de Elasticidad/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Túnica Íntima/patología , Túnica Media/patologíaRESUMEN
BACKGROUND: Biglycan (BGN), an extracellular matrix proteoglycan, has been shown to convey pro-inflammatory signals. In the present study we investigated BGN expression and its correlation with plasma levels of inflammatory markers in hypertensive subjects with or without alteration of carotid intima media thickness (IMT). METHODS: We evaluated 123 untreated essential hypertensives with no additional risk factors for atherosclerosis nor signs of cardiovascular disease and 40 controls. Hypertensives were classified according to a normal (< or =1 mm) or increased (>1 mm) IMT. BGN-mRNA and protein expression were measured in unstimulated, LPS- and Angiotensin II (Ang-II)-stimulated blood monocytes. Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and high sensitivity-C-reactive protein (hs-CRP) were also measured. RESULTS: We found increased levels of IL-6, TNF-alpha, hs-CRP, and BGN-mRNA and protein in hypertensives vs controls (1.72+/-0.60 vs 1 n-fold, and 3.60+/-0.75 vs 1 n-fold, both p<0.001). However, BGN expression was not significantly different between hypertensives with IMT < or =1 mm and >1 mm. Furthermore, in vitro addition of Ang II enhanced basal BGN-mRNA (in hypertensives: 3.57+/-1.08 vs 1.72+/-0.60 n-fold, p<0.001) and protein (in hypertensives: 4.92+/-0.42 vs 3.41+/-0.75, p<0.001) expression in monocytes. CONCLUSIONS: Our data provide evidence of an enhanced expression of BGN in essential hypertension. In addition we suggest that Ang II can mediate monocyte BGN production.
Asunto(s)
Arterias Carótidas/patología , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Regulación de la Expresión Génica , Hipertensión/genética , Hipertensión/fisiopatología , Proteoglicanos/genética , Proteoglicanos/metabolismo , Túnica Íntima/patología , Adulto , Angiotensina II/farmacología , Biglicano , Proteína C-Reactiva/metabolismo , Arterias Carótidas/anatomía & histología , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hipertensión/sangre , Hipertensión/patología , Interleucina-6/sangre , Lipopolisacáridos/inmunología , Macrófagos/metabolismo , Masculino , Monocitos/efectos de los fármacos , Monocitos/inmunología , Monocitos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Regresión , Factor de Necrosis Tumoral alfa/sangre , Túnica Íntima/anatomía & histologíaRESUMEN
BACKGROUND AND AIMS: Aging is associated with an increased risk of developing atherosclerosis. Subjects over 80 years of age without cardiovascular disease provide a model to investigate the protective factors increasing their resistance to atherosclerotic disease. Platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme associated with low density lipoprotein (LDL) and high density lipoprotein (HDL) inactivating platelet-activating factor (PAF) and preventing LDL oxidation by hydrolysis of oxidized phospholipids. The aim of the present study was to evaluate the contribution of the PAFAH gene Arg92His, Ile198Thr and Ala379Val polymorphisms to resistance toward developing cardiovascular events in healthy Sicilian octogenarians. METHODS: Distribution of PAF-AH genotypes and activity, and biochemical parameters, were compared between 100 octogenarians and 200 healthy adults. RESULTS: The individuals in the elderly group displayed significantly higher levels of HDL-C (p<0.001) and plasma (p<0.001) and HDL (p<0.001) PAF-AH activity. Analysis of PAFAH genotype distributions showed no significant differences between octogenarians and controls. No differences among PAF-AH genotypes with respect to plasma and HDL PAF-AH activity were found in either group. CONCLUSIONS: Our results provide no evidence of a significant association between the PAF-AH gene Arg92His, Ile198Thr and Ala379Val polymorphisms and successful aging in Sicilians. They also emphasize that, in these subjects, aging is characterized by increased levels of PAF-AH activity and HDL-C.
Asunto(s)
1-Alquil-2-acetilglicerofosfocolina Esterasa/sangre , 1-Alquil-2-acetilglicerofosfocolina Esterasa/genética , Envejecimiento/sangre , Envejecimiento/genética , Lipoproteínas HDL/sangre , Polimorfismo de Nucleótido Simple , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos , Aterosclerosis/sangre , Aterosclerosis/enzimología , Aterosclerosis/genética , Secuencia de Bases , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/enzimología , Enfermedades Cardiovasculares/genética , HDL-Colesterol/sangre , Cartilla de ADN/genética , Femenino , Humanos , Italia , MasculinoRESUMEN
BACKGROUND: Serum paraoxonase (PON1), a high density lipoprotein (HDL)-bound antioxidant enzyme, plays a role in atherosclerosis. An increase in PON1 activity has been reported following statin treatment. OBJECTIVE: In the present study the following factors were evaluated: the influence of PON1 gene Q192R, L55M and T(-107)C polymorphisms on the response of LDL oxidisability and PON1 activity to atorvastatin treatment. RESEARCH DESIGN AND METHODS: 205 Sicilian subjects with primary hypercholesterolaemia (HCh) and 69 healthy subjects as controls were concurrently enrolled. Hypercholesterolaemic patients were randomly divided into two groups: an atorvastatin group (10 mg/day atorvastatin) and a placebo group. Lipid profile, markers of LDL resistance to in vitro oxidation (lag-phase, oxidation rate and thiobarbituric acid-reactive substances), vitamin E content in LDL, PON1 activity and genotypes in both HCh and control subjects were determined at baseline. The same parameters were measured again after 3 weeks of treatment in both the atorvastatin and placebo groups. RESULTS: HCh subjects showed significantly lower LDL resistance to oxidation, vitamin E content and PON1 activity levels than controls. A strong association was found among PON1 T(-107)C genotypes, LDL susceptibility to oxidation, vitamin E content and PON1 activity. After treatment, the atorvastatin group displayed a significant decrease in total cholesterol, LDL-cholesterol levels, and LDL susceptibility to oxidation, and an increase in vitamin E content and PON1 activity, compared with baseline values. Unlike PON1 activity levels, no difference among PON1 gene polymorphisms and reduction in markers of LDL oxidisability was observed. CONCLUSIONS: These results show, for the first time, that atorvastatin is able to improve the resistance to LDL oxidation independently of PON1 gene polymorphism.