Mechanisms of coronary microvascular adaptation to obesity

Abstract

The metabolic syndrome (MetS) is associated with clustering of cardiovascular risk factors in individuals that may greatly increase their risk of developing coronary artery disease. Obesity and related metabolic dysfunction are the driving forces in the prevalence of MetS. It is believed that obesity has detrimental effects on cardiovascular function, but its overall impact on the vasomotor regulation of small coronary arteries is still debated. Emerging evidence indicates that in obesity coronary arteries adapt to hemodynamic changes via maintaining and/or upregulating cellular mechanism(s) intrinsic to the vascular wall. Among other factors, endothelial production of cyclooxygenase-2-derived prostacyclin and reactive oxygen species, as well as increased nitric oxide sensitivity and potassium channel activation in smooth muscle cells, have been implicated in maintaining coronary vasodilator function. This review aims to examine studies that have been primarily focused on alterations in coronary vasodilator function in obesity. A better understanding of cellular mechanisms that may contribute to coronary microvascular adaptation may provide insight into the sequence of pathological events in obesity and may allow the harnessing of these effects for therapeutic purposes.

Role of Adipose Tissue Endothelial ADAM17 in Age-Related Coronary Microvascular Dysfunction

“…Such maintained or even enhanced vasodilator capacity of coronary microvessels may imply vascular adaptations to hemodynamic and/or metabolic changes in the heart early on in obesity, a debated phenomenon, which is often implicated in obesity paradox. 36, 37 We 23 and others 24, 38 reported that aging of obese mice or rats, however, induces a prominent impairment in vasodilator function in mesenteric and skeletal muscle arteries. Similarly, in this study we found a significant age-related decline in human coronary arteriole dilator function in both obese men and women, but not in lean patients.…”

Body adiposity dictates different mechanisms of increased coronary reactivity related to improved in vivo cardiac function

“…Previous studies suggest that obesity may reduce NO levels mostly through increased oxidative stress [46] and that when NO bioavailability is reduced a compensatory mechanism takes place in order to maintain a normal coronary function [47]. Adaptation of coronary vessels is particularly important, as in the coronary circulation oxygen extraction is near maximal and any mismatch between blood supply and metabolic demand would deteriorate myocardial contractile function [48].…”

Functional network analysis of obese and lean Göttingen minipigs elucidates changes in oxidative and inflammatory networks in obese pigs

“…Peripheral vascular function showed a relative increased reactive hyperaemic response following cuff occlusion in obese compared to lean animals, but also in response to nitroglycerin, whereas coronary artery sensitivity for the dilating effect of substance P was lower, and for the calcium channel blocker nifedipine was significantly higher in obese as compared to lean. This apparent contradiction between vascular and endothelial function in different vascular beds and between lean and obese subjects has previously been shown in animal and human studies and maybe indicative of compensatory mechanisms in response to altered endothelial function or an altered physiological reserve in the obese [6,1]. Thus, in general, a number of parameters usually associated with obesity were not significantly different between obese and lean animals.…”