Nutritional Control, Gene Regulation, and Transformation of Vascular Smooth Muscle Cells in Atherosclerosis

Abstract

Contractile-state smooth muscle cells (SMC), the only cell type in the arterial media, undergoes migration to the intima, proliferation, and abundant extracellular matrix production during the early stages of atherosclerosis. This involves the ingestion of low-density lipoprotein (LDL) and modified or oxidised LDL by macrophages together with SMC by several pathways including a scavenger pathway leading to accumulation of cholesterol esters and formation of foam cells. High-plasma cholesterol levels constitute a major causative risk for atherosclerosis. The membrane-bound transcription factor called sterol regulatory element binding protein (SREBP) activates gene-encoding enzymes of cholesterol and fatty acid biosynthesis. The SREBP expression, in response to diet, shows that are involved in both lipogenesis and cholesterol homeostasis, moreover SREBPs are regulated directly by cholesterol. Animal models were used in trials of atherosclerosis, and cholesterol feeding has been described elsewhere as producing atherosclerotic lesions. We have examined the morphological, molecular and proliferative change in arterial SMC mimicking such a cholesterol diet, this transformed SMC is a good model to study the alterations of the differentiated state of SMC, and the transformation into foam cell, caused by cholesterol-rich diet. Despite the complexity of the interactions in atherosclerosis, there are many opportunities to affect the homeostatic balance of the artery wall at SMC levels. We have considered here some of the possible targets for intervention with promising strategies for the nutritional control of the genes, and, in a general way, the possibilities for modulating the expression of genes influencing atherosclerosis.

Deleted in Breast Cancer 1 (DBC1) Protein Regulates Hepatic Gluconeogenesis

“…A variety of hormones and dietary signals that control glucose synthesis target the expression of PEPCK, given that this enzyme catalyzes the first committed step of gluconeogenesis (4). In mouse models, overexpression of PEPCK is enough to induce glucose intolerance (30), and even a modest reduction in PEPCK expression is able to ameliorate fasting glucose levels and glucose tolerance (31).…”

Cyclic fluctuations of 3‐hydroxy‐3‐methylglutaryl‐CoA reductase in aortic smooth muscle cell cultures

“…These results suggest that the cholesterol diet induces change in HMG-CoA reductase gene expression in SMC cultures before the morphologic transformation of the SMC in the artery wall (53). SMC in vivo were shown to increase cholesterol biosynthesis significantly and decrease the intracellular cholesterol efflux associated with phenotype changes in SMC in culture (54,55).…”

Serotonin Effects on Expression of the LDL Receptor Family Member LR11 and 7-Ketocholesterol–Induced Apoptosis in Human Vascular Smooth Muscle Cells

“…These reports propose that the presence of 7KCHO may reduce the number of VSMCs and contribute to unstable plaque. Generally, proliferation/apoptosis and dediferentiation of VSMCs in the arterial intima identify one of the pathological indings observed in atherogenesis [2,13,14]. Meanwhile, the factors modulating proliferation/ apoptosis of VSMCs and the potential cellular mechanisms are not fully elucidated.…”