Insulin Resistance and Endothelial Dysfunction Constitute a Common Therapeutic Target in Cardiometabolic Disorders

Abstract

Insulin resistance and other risk factors for atherosclerosis, such as hypertension and hypercholesterolemia, promote endothelial dysfunction and lead to development of metabolic syndrome which constitutes an introduction to cardiovascular disease. The insulin resistance and endothelial dysfunction cross talk between each other by numerous metabolic pathways. Hence, targeting one of these pathologies with pleiotropic treatment exerts beneficial effect on another one. Combined and expletive treatment of hypertension, lipid disorders, and insulin resistance with nonpharmacological interventions and conventional pharmacotherapy may inhibit the transformation of metabolic disturbances to fully developed cardiovascular disease. This paper summarises the common therapeutic targets for insulin resistance, endothelial dysfunction, and vascular inflammatory reaction at molecular level and analyses the potential pleiotropic effects of drugs used currently in management of cardiovascular disease, metabolic syndrome, and diabetes.

Insulin Resistance Is a Risk Factor for Silent Lacunar Infarction

“…Both IR and endothelial dysfunction are commonly observed in many cardiovascular diseases. 36,37 The link between IR and endothelial dysfunction is explained by some molecular and cellular mechanisms. IR increases lipolysis and induces proinflammatory cytokines.…”

“…Such lipotoxicity and inflammation may contribute to endothelial dysfunction, explaining the link between IR and endothelial dysfunction. 36,37 Thus, IR may lead to the development of SLI, via both endothelial dysfunction and atherosclerosis. In this study, we investigated the association of C-reactive protein, which is one of known inflammatory marker associated with both atherosclerosis 38 and endothelial dysfuntion, 39 with SLI.…”

Comparative Effectiveness of Combination Therapy with Statins and Angiotensin‐Converting Enzyme Inhibitors versus Angiotensin II Receptor Blockers in Patients with Coronary Heart Disease: A Nationwide Population‐Based Cohort Study in Korea

“…Hyperlipidemia and hypertension are the most prevalent but modifiable risk factors that commonly coexist in patients with established CHD, and these were well represented in our population (95% or more of our patients had both of these risk factors). Studies have emphasized the importance of controlling both risk factors to minimize CV morbidity and mortality . The first‐line therapies for hyperlipidemia and hypertension, statins and RAAS blockers, have the potential to exert synergistic results when used together; thus it seemed reasonable to assess combination therapy with these agents and compare different RAAS blockers.…”

Atheroprotective Effects and Molecular Targets of Tanshinones Derived From Herbal Medicine Danshen

“…The endothelium, the first‐line defense in the blood vessel, is regarded as the gatekeeper of vascular health and diseases . Alteration of functional properties of endothelium leads to endothelial dysfunction and multiple cardiometabolic diseases, such as atherosclerosis, hypertension, and diabetes . Endothelial dysfunction is an early event in the development of atherosclerosis, which consists of endothelial injury, increased monocyte adhesion to endothelial cells, impaired endothelium‐dependent vasorelaxation, inflammation, vascular aging, and augmented oxidative stress .…”

“…51 Alteration of functional properties of endothelium leads to endothelial dysfunction and multiple cardiometabolic diseases, such as atherosclerosis, hypertension, and diabetes. 52 Endothelial dysfunction is an early event in the development of atherosclerosis, which consists of endothelial injury, increased monocyte adhesion to endothelial cells, impaired endothelium-dependent vasorelaxation, inflammation, vascular aging, and augmented oxidative stress. 53 One central mechanism of protecting endothelial dysfunction is endothelial nitric oxide synthase (eNOS) dependent nitric oxide (NO) production, which represents a promising anti-atherosclerotic target in cardiovascular therapeutics.…”