Heart of the matter: Coronary dysfunction in metabolic syndrome

Abstract

Metabolic syndrome (MetS) is a collection of risk factors including obesity, dyslipidemia, insulin resistance/impaired glucose tolerance, and/or hypertension. The incidence of obesity has reached pandemic levels, as ~20–30% of adults in most developed countries can be classified as having MetS. This increased prevalence of MetS is critical as it is associated with a two-fold elevated risk for cardiovascular disease. Although the pathophysiology underlying this increase in disease has not been clearly defined, recent evidence indicates that alterations in the control of coronary blood flow could play an important role. The purpose of this review is to highlight current understanding of the effects of MetS on regulation of coronary blood flow and to outline the potential mechanisms involved. In particular, the role of neurohumoral modulation via sympathetic α-adrenoceptors and the renin-angiotensin-aldosterone system (RAAS) are explored. Alterations in the contribution of end-effector K+, Ca2+, and transient receptor potential (TRP) channels are also addressed. Finally, future perspectives and potential therapeutic targeting of the microcirculation in MetS are discussed.

Impaired coronary flow reserve evaluated by echocardiography is associated with increased aortic stiffness in patients with metabolic syndrome: an observational study

“…MetS impairs the ability of the coronary circulation to regulate vascular resistance and balance myocardial oxygen supply and demand (9). All the components of MetS (hypertension, dysglycemia, dyslipidemia, and obesity) can individually impair microvascular function (10,28,31).…”

“…All the components of MetS (hypertension, dysglycemia, dyslipidemia, and obesity) can individually impair microvascular function (10,28,31). Exact mechanisms underlying impaired pharmacologic coronary vasodilation in MetS have not been clearly defined, but are likely related to altered functional expression of receptors and ion channels, endothelial and vascular smooth muscle function, paracrine and neuroendocrine influences, structural remodeling of coronary arterioles and/or microvascular rarefaction (9). Coronary vasomotor dysfunction in the MetS is related to chronic activation of the renin-angiotensin and sympathetic nervous system that leads to augmented angiotensin II tip 1 and alpha 1-adrenoceptor mediated coronary vasoconstriction (5,32).…”

“…MetS impairs the ability of the coronary circulation to regulate vascular resistance and balance myocardial oxygen supply and demand (4,5). Coronary microvascular dysfunction in MetS is evidenced by reduced coronary venous PO 2 , diminished vasodilation to endothelial-dependent and independent agonist and altered functional and reactive hyperemia (4)(5)(6)(7)(8)(9). Alterations in coronary microvascular function could contributed to the increased cardiovascular morbidity and mortality observed in patients with MetS (10).…”

Perioperative management of the severely obese patient: a selective pathophysiological review

“…Coronary vasodilatation in response to pharmacological or metabolic stimuli is reduced, and coronary autoregulation is inhibited. 19 The impact on myocardial oxygenation may become evident in settings where coronary flow reserve is an important defense mechanism, e.g., during exercise or cardiac ischemia. On the other hand, the response of the coronary circulation to vasoconstrictor agents, such as angiotensin II (circulating or locally produced by adipocytes) and alpha-1 receptor agonists, is enhanced in animal models of the metabolic syndrome, 20 and this is in keeping with the increased activity of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system often found in MetS.…”

The Adrenergic System in Vascular Smooth Muscle

“…The α 1 -adrenoceptor vasoconstriction may reduce retrograde coronary flow caused by systolic ventricular contraction and so help maintain blood flow to the deeper regions of the left ventricle [96]. However, the presence of α 1 -adrenoceptors can lead to enhanced vasoconstriction in pathophysiological situations such as metabolic syndrome, and this may also be linked to diminished β-adrenoceptor-mediated dilatation [11]. In coronary atherosclerosis, damage to the vascular endothelium may also be a factor in the shift of the balance towards vasoconstriction [120].…”