Angiotensin II, Hypercholesterolemia, and Vascular Smooth Muscle Cells: A Perfect Trio for Vascular Pathology

Abstract

Cardiovascular disease is the leading cause of morbidity and mortality in the Western and developing world, and the incidence of cardiovascular disease is increasing with the longer lifespan afforded by our modern lifestyle. Vascular diseases including coronary heart disease, high blood pressure, and stroke comprise the majority of cardiovascular diseases, and therefore represent a significant medical and socioeconomic burden on our society. It may not be surprising that these conditions overlap and potentiate each other when we consider the many cellular and molecular similarities between them. These intersecting points are manifested in clinical studies in which lipid lowering therapies reduce blood pressure, and anti-hypertensive medications reduce atherosclerotic plaque. At the molecular level, the vascular smooth muscle cell (VSMC) is the target, integrator, and effector cell of both atherogenic and the major effector protein of the hypertensive signal Angiotensin II (Ang II). Together, these signals can potentiate each other and prime the artery and exacerbate hypertension and atherosclerosis. Therefore, VSMCs are the fulcrum in progression of these diseases and, therefore, understanding the effects of atherogenic stimuli and Ang II on the VSMC is key to understanding and treating atherosclerosis and hypertension. In this review, we will examine studies in which hypertension and atherosclerosis intersect on the VSMC, and illustrate common pathways between these two diseases and vascular aging.

The Effects of Angiotensin II or Angiotensin 1-7 on Rat Pial Microcirculation during Hypoperfusion and Reperfusion Injury: Role of Redox Stress

“…In the rat model used in this study, at the end of reperfusion Ang II caused massive microvascular leakage along the venular networks, causing interstitial edema and compromising the capillary viability, while ROS formation increased, indicating marked oxidative stress. Our data support previous studies that evaluated the effects caused by angiotensin II in different pathophysiological conditions, such as hypertension and hypercholesterolemia [ 34 , 35 ]. Ang 1-7 did not affect microvascular vessels under baseline conditions, but it was able to reduce extravascular leakage and counteract the increase in ROS.…”

Edible and Herbal Plants for the Prevention and Management of COVID-19

“…Cardiovascular diseases in COVID-19 patients involves IL-6, ACE2, and angiotensin as the critical mediators that drive the pathological process. The increased IL-6 from activated macrophages and endothelial and smooth muscle cells after SARS-CoV-2 infection promotes the generation of MCP-1, upregulates the expression of cell adhesion molecules, and motivates the proliferation and migration of vascular smooth muscle cells, thus promoting atherogenesis (St Paul et al, 2020). Therefore, the level of circulating IL-6 may be a risk predictor of cardiovascular events in COVID-19.…”

Pyk2/MCU Pathway as a New Target for Reversing Atherosclerosis

“…Meanwhile, by reviewing the literature, it was reported that angiotensin II (Ang II) stimulated a calcium-sensitive tyrosine kinase Pyk2 via the type-1 angiotensin II (AT1) receptor in pulmonary vein endothelial cells (PVECs) and vascular smooth muscle cells (VSMCs) ( Tang et al, 2000 ; Satoh et al, 2001 ; Nakashima et al, 2006 ). In the endothelial cells, Ang II binds to EC receptors and facilitates the expression of plasminogen activator inhibitor-1 and cell adhesion molecules, which may promote the development of atherosclerosis and myocardial infarction ( Luscinskas and Gimbrone, 1996 ; St Paul et al, 2020 ), due to promoting ROS generation, increasing the cell-surface expression of cell adhesion molecules, and enhancing leukocyte adhesiveness to ECs, eventually causing endothelium dysfunction. Would the presence of Ang II and EC injury in the initial stage of atherosclerosis activate the Pyk2/MCU pathway (further aggravating the progression of the disease)?…”