Vascular smooth muscle remodeling in health and disease

Abstract

In blood vessels, vascular smooth muscle cells (VSMCs) generally exist in two major phenotypes: contractile and non-contractile (synthetic). The contractile phenotype is predominant and includes quiescent or differentiated VSMCs, which function as the regulators of blood vessel diameter and blood flow. According to some literature in the field, contractile VSMCs do not switch to the non-contractile phenotype due to the activation of specific transcription factors that are considered as guardians of the contractile phenotype. However, a vast literature uses the terms remodeling and phenotype switching of contractile VSMCs interchangeably mainly based on studies dealing with atherosclerosis. The use of the terms remodeling and switching to describe changes in phenotype based on morphological criteria can be confusing. The term remodeling was first used to describe morphological changes in the heart and was soon used to describe phenotype changes of contractile VSMCs based on morphological criteria. The latter were introduced in early studies, and new molecular criteria were later added, including changes in gene expression, which could be irreversible. In this review, we will discuss the different views concerning remodeling and possible switching of contractile VSMCs to a non-contractile phenotype. We conclude that only remodeling of contractile VSMCs may take place upon vascular injury and disease.

High Na+ Salt Diet and Remodeling of Vascular Smooth Muscle and Endothelial Cells

“…From a macroscopic perspective, this system is divided into three major categories: veins (afferent vessels operating in a low-pressure system), arteries (efferent blood vessels operating in a high-pressure system), and capillaries (connecting veins and arteries). Microscopically, except the capillaries, artery and vein histological organization and their tissue composition are similar and divided into three major tunics or layers ( Figure 1 ) [ 2 ].…”

“…On the surface, there is the tunica externa or adventitia, which is composed of loosely intertwined collagen fibers and fibroblasts ( Figure 1 ) [ 2 ]. Between the circulating blood and the vascular wall is the tunica interna or intima, consisting primarily of a monolayer of vascular endothelial cells (VECs) ( Figure 1 ) [ 2 ].…”

“…On the surface, there is the tunica externa or adventitia, which is composed of loosely intertwined collagen fibers and fibroblasts ( Figure 1 ) [ 2 ]. Between the circulating blood and the vascular wall is the tunica interna or intima, consisting primarily of a monolayer of vascular endothelial cells (VECs) ( Figure 1 ) [ 2 ]. Finally, between the intima and the adventitia lies the tunica media or media composed of abundant elastic fibers and particularly contractile vascular smooth muscle cells (VSMCs), which control the vessel tone ( Figure 1 ).…”

“…However, VECs are roughly 30–50 µm in length, 10–30 µm wide, and a thickness of 0.1–10 µm. Both cell types are of multiple embryonic origins (neural crests, mesoderm) [ 2 , 3 ].…”

“…Due to the complexity of their origin during early embryogenesis, understanding the differentiation of these cells remains a significant challenge [ 2 , 4 ]. Under physiological conditions, contractile VSMCs in mature blood vessels exhibited a low rate of synthesis of extracellular matrix components and was characterized by a series of highly regulated smooth muscle markers, such as cytoskeletal and contractile proteins, which include smooth muscle actin, myosin heavy chain, calponin, and smooth muscle 22 alpha (SM22α), as well as signaling molecules [ 2 , 4 , 5 , 6 ]. All are required for the primary function of VSMCs [ 4 , 7 ].…”