Coronary microvascular disease as an early culprit in the pathophysiology of diabetes and metabolic syndrome

Abstract

Metabolic syndrome (MetS) is a group of cardio-metabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia; these are also a combination of independent coronary artery disease (CAD) risk factors. Alarmingly, the prevalence of MetS risk factors are increasing and a leading cause for mortality. In the vasculature, complications from MetS and type 2 diabetes (T2D) can be divided into microvascular (retinopathy and nephropathy) and macrovascular (cardiovascular diseases and erectile dysfunction). In addition to vascular and endothelial dysfunction, vascular remodeling and stiffness are also hallmarks of cardiovascular disease (CVD), and well-characterized vascular changes that are observed in the early stages of hypertension, T2D, and obesity (1-3). In the heart, the link between obstructive atherosclerosis of coronary macrovessels and myocardial ischemia (MI) is well established. However, recent studies show that abnormalities in the coronary microcirculation are associated with functional and structural changes in coronary microvessels (classically defined as being <150-200 μm internal diameter), which may cause or contribute to MI even in the absence of obstractive CAD. This suggests a prognostic value of an abnormal coronary microcirculation as an early sub-clinical culprit in the pathogenesis and progression of heart disease in T2D and MetS. The aim of this review is to summarize recent studies investigating the coronary microvascular remodeling in an early pre-atherosclerotic phase of MetS and T2D, and to explore potential mechanisms associated with the timing of coronary microvascular remodeling relative to that of the macrovasculature.

Subclinical systolic and diastolic dysfunctions in patients with metabolic syndrome and angiographically normal coronary arteries: An echocardiographic study

“…Additionally, all patients in this study had normal coronary arteries; therefore, the diastolic dysfunction could not be caused by epicardial coronary artery disease. Several animal and human studies have shown that MetS and type 2 diabetes mellitus can lead to abnormal coronary microcirculation as an initial subclinical culprit in the development of heart diseases . Macrovascular remodeling occurs at a later stage, and is attributed to the progression of atherosclerotic plaques induced by MetS components …”

“…Macrovascular remodeling occurs at a later stage, and is attributed to the progression of atherosclerotic plaques induced by MetS components. 17 Ivanovic et al 7 reported that the Tei index as an indicator of global LV function was associated with systemic hypertension, diabetes mellitus, and an increased levels of triglyceride, but not decreased levels of high-density lipoprotein and higher weight.…”

Chloroquine differentially modulates coronary vasodilation in control and diabetic mice

“…Ischaemia due to coronary artery disease is caused by occlusion or narrowing vessels as a result of lipid plaque formation, whereas the patient with coronary microvascular disease shows a clear angiograph with reduced coronary flow due to attenuated relaxation in the distal artery and reduced number of capillaries. Coronary endothelial dysfunction is implicated in the development of both coronary macrovascular and microvascular diseases (Belin de Chantemele & Stepp, ; Labazi & Trask, ; Pant et al, ; Pepine et al, ; Rocic, ). Therefore, we examined the effect of chloroquine on coronary endothelial function in control and diabetic mice.…”

“…Diabetic patients exhibit a higher morbidity of malaria infection (Danquah, Bedu-Addo, & Mockenhaupt, 2010) & Stepp, 2012;Labazi & Trask, 2017;Pant et al, 2014;Pepine et al, 2015;Rocic, 2012). Therefore, we examined the effect of chloroquine on coronary endothelial function in control and diabetic mice.…”

“…Chronic hyperglycaemia leads to cardiovascular complications that are a leading cause of death in diabetic patients. Endothelial cell (EC) dysfunction is a major cause of vascular complications in diabetes, while coronary endothelial dysfunction is implicated in the increased morbidity of coronary artery disease and coronary microvascular disease in diabetes (Belin de Chantemele & Stepp, 2012;Labazi & Trask, 2017;Pant, Marok, & Klein, 2014;Pepine et al, 2015;Rocic, 2012). It is therefore scientifically important and clinically relevant to examine whether chloroquine has a maladaptive effect on coronary endothelial function in diabetes.…”