Metabolism of vascular smooth muscle cells in vascular diseases

Abstract

Vascular smooth muscle cells (VSMCs) are the fundamental component of the medial layer of arteries and are essential for arterial physiology and pathology. It is becoming increasingly clear that VSMCs can alter their metabolism to fulfill the bio-energetic and biosynthetic requirements. During vascular injury, VSMCs switch from a quiescent "contractile" phenotype to a highly migratory and proliferative "synthetic" phenotype. Recent studies find that the phenotype switching of VSMCs is driven by a metabolic switch. Metabolic pathways, including aerobic glycolysis, fatty acid oxidation, and amino acid metabolism, have distinct, indispensable roles in normal and dysfunctional vasculature. VSMCs metabolism is also related to the metabolism of endothelial cells. In the present review, we present a brief overview of VSMCs metabolism, and how it regulates the progression of several vascular diseases, including atherosclerosis, systemic hypertension, diabetes, pulmonary hypertension, vascular calcification, and aneurysms, and the effect of the risk factors for vascular disease (aging, cigarette smoking and excessive alcohol drinking) on VSMCs metabolism, to clarify the role of VSMCs metabolism in the key pathological process.

Disease-Relevant Single Cell Photonic Signatures Identify S100β Stem Cells and their Myogenic Progeny in Vascular Lesions

“…Indeed, it is known that glucose catabolism due to cellular differentiation increases relative to oxidative phosphorylation during periods of biosynthesis with significant carbon demands [69] . In fully differentiated cells, such as medial SMCs, efficient ATP production is valuable, and accordingly, these cells primarily rely on oxidative phosphorylation, producing a high baseline optical redox ratio of FAD/ [NAD(P)H+FAD] [70]. While we clearly demonstrate upregulation of glycolytic metabolism in cells upon myogenic stimulation (even in the presence of oxygen) akin to the "Warburg effect", the precise species involved were not specifically addressed in the current manuscript.…”

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

“…Independent of structural changes, there is also recent evidence linking cell metabolism to transcriptional activity during differentiation/de-differentiation cycles that may contribute to changes in the photonic profile of these cells [67], Indeed, it is known that glucose catabolism due to cellular differentiation increases relative to oxidative phosphorylation during periods of biosynthesis with significant carbon demands [68]. In fully differentiated cells, such as medial SMCs, efficient ATP production is valuable, and accordingly, these cells primarily rely on oxidative phosphorylation, producing a high baseline optical redox ratio of FAD/[NAD(P)H+FAD] [71], While we clearly demonstrate upregulation of glycolytic metabolism in cells upon myogenic stimulation (even in the presence of oxygen) akin to the “Warburg effect”, the precise species involved were not specifically addressed in the current manuscript. NADPH is routinely utilized in the maintenance of pools of glutathione, thioredoxin, and peroxiredoxins, which help to create a reductive environment after oxidative damage produced by processes such as inflammation or ischemia, typical of vascular injury [72], Quantifying NAD(P)H and FAD fluorescence through an optical redox ratio and fluorescence lifetime imaging (FLIM) can provide sensitivity to the relative balance between oxidative phosphorylation and glucose catabolism.…”

Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation

“…Increased glycolysis appears to be critical for the bioenergetic shift that occurs during proliferation and migration of VSMCs [ 8 , 10 ]. Growth factor-treated VSMCs exhibit enhanced glycolytic flux and express markers of the synthetic VSMC phenotype [ 5 , 36 , 37 ]. We previously identified LDHA, which catalyzes the final step of glycolysis, as a therapeutic target for uncontrolled proliferation and migration of VSMCs [ 38 ].…”

“…Fully differentiated VSMCs remain in a non-proliferative state under normal conditions, while VSMCs dedifferentiate and their proliferation rate increases upon vascular injury [ 2 , 3 ]. Phenotypic switching of VSMCs in response to various physiological and pathological factors has long been considered of fundamental importance for proliferation and migration of VSMCs and pathological intima formation, which leads to the development of various vascular diseases including atherosclerosis, transplant vasculopathy, and pulmonary hypertension [ 4 , 5 ]. Thus, better understanding of the underlying mechanism might lead to the identification of a new therapeutic target for neointimal hyperplasia.…”