The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles

Abstract

Vascular smooth muscle cells (VSMCs) are the stromal cells of the vascular wall, continually exposed to mechanical signals and biochemical components generated in the blood compartment. They are involved in all the physiological functions and the pathological changes taking place in the vascular wall. Owing to their contractile tonus, VSMCs of resistance vessels participate in the regulation of blood pressure and also in hypertension. VSMCs of conduit arteries respond to hypertension-induced increases in wall stress by an increase in cell protein synthesis (hypertrophy) and extracellular matrix secretion. These responses are mediated by complex signalling pathways, mainly involving RhoA and extracellular signal-regulated kinase1/2. Serum response factor and miRNA expression represent main mechanisms controlling the pattern of gene expression. Ageing also induces VSMC phenotypic modulation that could have influence on cell senescence and loss of plasticity and reprogramming. In the early stages of human atheroma, VSMCs support the lipid overload. Endocytosis/phagocytosis of modified low-density lipoproteins, free cholesterol, microvesicles, and apoptotic cells by VSMCs plays a major role in the progression of atheroma. Migration and proliferation of VSMCs in the intima also participate in plaque progression. The medial VSMC is the organizer of the inwardly directed angiogenic response arising from the adventitia by overexpressing vascular endothelial growth factor in response to lipid-stimulated peroxisome proliferator-activated receptor-γ, and probably also the organizer of the adventitial immune response by secreting chemokines. VSMCs are also involved in the response to proteolytic injury via their ability to activate blood-borne proteases, to secrete antiproteases, and to clear protease/antiprotease complexes.

Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium

“…In addition, in the co-cultured system with HUVECs and VSMCs, a significant increase in both PAI-1 secretion from HUVECs and intracellular PAI-1 expression in VSMCs were observed (Gallicchio et al 1994). Physiological fibrinolysis in VSMCs is controlled by specific molecules and affected by the presence of other cytokines secreted from adjacent cells (Lacolley et al 2012).…”

Thrombospondin-1, -2 and -5 have differential effects on vascular smooth muscle cell physiology

“…The individual processes listed in the "Cardiovascular System Development and Function" annotation heavily represent the migration, proliferation and differentiation and activation of ECs. While VSMC-induced signaling of ECs is a well-documented phenomenon [16], these findings may also represent a bias due to a much greater body of research on apoptosis-related genes and their functions in ECs.…”

Development of Human Umbilical Vessels in The Second Trimester of Pregnancy: Histological, Immunohistochemical and Morphometric Study

“…Second, SMCs of the neointima revealed negative immune staining for alpha smooth muscle actin denoting lack of contractile function. According to Lacolley et al [20] neointima is mainly constituted by vascular SMCs of subjacent media. These SMCs partially lose their contractile phenotype and acquire a synthetic one during their migration and intimal proliferation.…”

“…Vascular SMCs the main stromal cells of vascular wall assume structural and physiological functions. It synthesizes the extracellular matrix during development and provide arterial wall with the capacity of withstanding high pressure of circulating blood [10,20] . In addition, the vascular SMCs possess fibroblastic function producing collagen and elastin in the developing media hence collagen content in the vessel wall is a reflection of SMC maturity [8] .…”