Obesity and Coronary Microvascular Disease – Implications for Adipose Tissue-Mediated Remote Inflammatory Response

Abstract

It is believed that obesity has detrimental effects on the coronary circulation. These include immediate changes in coronary arterial vasomotor responsiveness and the development of occlusive large coronary artery disease. Despite its critical role in regulating myocardial perfusion, the altered behavior of coronary resistance arteries, which gives rise to coronary microvascular disease (CMD) is poorly understood in obesity. A chronic, low-grade vascular inflammation has been long considered as one of the main underlying pathology behind CMD. The expanded adipose tissue and the infiltrating macrophages are the major sources of pro-inflammatory mediators that have been implicated in causing inadequate myocardial perfusion and, in a long term, development of heart failure in obese patients. Much less is known the mechanisms regulating the release of these cytokines into the circulation that enable them to exert their remote effects in the coronary microcirculation. This mini review aims to examine recent studies describing alterations in the vasomotor function of coronary resistance arteries and the role of adipose tissue-derived pro-inflammatory cytokines and adipokines in contributing to CMD in obesity. We provide examples of regulatory mechanisms by which adipokines are released from adipose tissue to exert their remote inflammatory effects on coronary microvessels. We identify some of the important challenges and opportunities going forward.

Endothelium‐dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction

“…Patients with obesity in general display lower coronary microvascular density, 29 which when combined with alterations in vasomotor function related to adipose tissue-derived pro-inflammatory cytokines, are believed to contribute to CMD in obesity. 26,30,31 The consequent reductions in myocardial blood flow in obesity-related HFpEF from microvascular dysfunction, 32 in combination with greater cardiac metabolic demand due to increases in ventricular mass, volume expansion, higher filling pressures, and greater cardiac output may result in a 'perfect storm' for the occurrence of myocardial oxygen supply-demand mismatch. The combination of these factors may further predispose to development of ischaemia in the setting of CMD by increasing myocardial oxygen demand in obesity-related HFpEF.…”

Integrated Physiologic Assessment of Ischemic Heart Disease in Real-World Practice Using Index of Microcirculatory Resistance and Fractional Flow Reserve

“…There is evidence that obesity is a contributor to coronary microvascular disease. 22 Expansion of adipose tissue leads to tissue hypoxia and results in an increased production of various cytokines (leptin, resistin, tumor necrosis factor, and interleukin-6). These secreted adipokines and proinflammatory cytokines can induce oxidative stress, which leads to reduced availability of nitric oxide and limits vasodilatory capacity.…”

Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk

“…Nevertheless, these molecules can also trigger remote inflammatory effects withy potential vascular changes as far as the retinal circulation, usually devoided of PVAT, therefore, resulting in abnormal vascular function at this level43. Further research is necessary to elucidate this point.…”