Article

Avogaro A, de Kreutzenberg SV. Mechanisms of endothelial dysfunction in obesity

Metabolic Diseases--Department of Clinical and Experimental Medicine, University of Padova, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy.
Clinica Chimica Acta (Impact Factor: 2.82). 11/2005; 360(1-2):9-26. DOI: 10.1016/j.cccn.2005.04.020
Source: PubMed

ABSTRACT Obesity is a chronic disease, whose incidence is alarmingly growing, affecting not only adults but also children and adolescents. It is associated with severe metabolic abnormalities and increased cardiovascular morbidity and mortality. Adipose tissue secretes a great number of hormones and cytokines that not only regulate substrate metabolism but may deeply and negatively influence endothelial physiology, a condition which may lead to the formation of the atherosclerotic plaque. In this review, the physiology of the endothelium is summarised and the mechanisms by which obesity, through the secretory products of adipose tissue, influences endothelial function are explained. A short description of methodological approaches to diagnose endothelial dysfunction is presented. The possible pathogenetic links between obesity and cardiovascular disease, mediated by oxidative stress, inflammation and endothelial dysfunction are described as well.

0 Followers
 · 
78 Views
 · 
0 Downloads
  • Source
    • "Thus, these complex mechanisms interact after exercise, leading to decreased PVR in most circumstances and to decreased CO in some circumstances. It is possible that, as in elderly, hypertensive, and overweight subjects, sympathetic activity (57,71) and cardiopulmonary reflexes (68) are exacerbated while endothelial function (57,60) and baroreflex control (72) are impaired, PVR decrease after exercise is mitigated, and CO decrease is facilitated, which may explain the differences in PAEH suggested by this review. Once again, this is just a hypothesis that should be investigated in the future. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Due to differences in study populations and protocols, the hemodynamic determinants of post-aerobic exercise hypotension (PAEH) are controversial. This review analyzed the factors that might influence PAEH hemodynamic determinants, through a search on PubMed using the following key words: ''postexercise'' or ''post-exercise'' combined with ''hypotension'', ''blood pressure'', ''cardiac output'', and ''peripheral vascular resistance'', and ''aerobic exercise'' combined only with ''blood pressure''. Forty-seven studies were selected, and the following characteristics were analyzed: age, gender, training status, body mass index status, blood pressure status, exercise intensity, duration and mode (continuous or interval), time of day, and recovery position. Data analysis showed that 1) most postexercise hypotension cases are due to a reduction in systemic vascular resistance; 2) age, body mass index, and blood pressure status influence postexercise hemodynamics, favoring cardiac output decrease in elderly, overweight, and hypertensive subjects; 3) gender and training status do not have an isolated influence; 4) exercise duration, intensity, and mode also do not affect postexercise hemodynamics; 5) time of day might have an influence, but more data are needed; and 6) recovery in the supine position facilitates systemic vascular resistance decrease. In conclusion, many factors may influence postexercise hypotension hemodynamics, and future studies should directly address these specific influences because different combinations may explain the observed variability in postexercise hemodynamic studies.
    Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 06/2014; 47(8):626. DOI:10.1590/1414-431X20143832 · 1.08 Impact Factor
  • Source
    • "Genetically obese mice develop endothelial dysfunction.31 In the current study, pharmacological MR antagonism prevented endothelial dysfunction in diet-induced obesity, suggesting that activation of MR with a concomitant release of inflammatory molecules impaired endothelium-dependent relaxation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Aims: Aldosterone plays a crucial role in cardiovascular disease. ‘Systemic’ inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the ‘endothelial’ MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. ..................................................................................................................................................................................... Methods and results: C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high ‘endogenous’ aldosterone) and in ‘exogenous’ aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. ..................................................................................................................................................................................... Conclusion: Obesity-induced endothelial dysfunction depends on the ‘endothelial’ MR and is mediated by an imbalance of oxida- tive stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.
    European Heart Journal 04/2013; 34(45). DOI:10.1093/eurheartj/eht095 · 14.72 Impact Factor
  • Source
    • "Nuclear Factor κB Activation contributes to vascular endothelial dysfunction via oxidative stress in overweight/obese middle-aged and older humans [38]. Modest weight loss can improve endothelial function and affect the entire cluster of coronary heart disease risk factors simultaneously [39]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiac syndrome X is an important therapeutic and diagnostic challenge to physician. Study of Csx patients may help to understand the pathophysiology of coronary microcirculation and to gain an insight on the management of these group patients. We measured the flow mediated dilation of the brachial artery both endothelium dependent and independent vasodilatation by high resolution ultrasound in 30 cardiac syndrome X patients and matched with 30 healthy control subjects. Significantly decreased flow mediated dilatation was observed in patients when compared to control (9.42±7.20 vs 21.11±9.16 p<0.01) but no significant difference was observed between groups in response to nitroglycerin (25.39±6.82 vs 28.87±8.69). Receiver operator characteristic analysis showed that value of <11.11 had sensitivity of 80%, specificity 86.67%, positive predictive value 76.66%, negative predictive value 83.33%. In total, 46% of subjects had endothelial dysfunction and of them, CSX subjects had higher prevalence (76% vs 16% p<0.01) than control subjects. Higher mean values of body mass index, systolic blood pressure and diastolic blood pressure was observed in subjects with FMD<11.11 than >11.11(p<0.01). In logistic regression analysis, FMD was significantly associated with systolic blood pressure (Odds ratio 1.122 95% CI 1.053-1.196 p<0.01) and body mass index (Odds 1.248 95%CI 0.995-1.56 p<0.05). The study suggests impairment of endothelial function in cardiac syndrome X patients. Increased Systolic blood pressure and body mass index may increase the risk of impairment of endothelial function in this group of patients.
    Cardiovascular Ultrasound 12/2011; 9:40. DOI:10.1186/1476-7120-9-40 · 1.28 Impact Factor
Show more