Myofibroblast Forms Atherosclerotic Plaques

Abstract

For decades, smooth muscle cells (SMCs) and macrophages are considered as the main contributors to atherosclerotic plaques. However, we found that in the human coronary atherosclerotic plaques, SMCs were few, while lots of myofibroblasts infiltrated in the intima near the lumen (fibrous cap) and their distribution was highly positive related to intimal thickness. In addition to lots of foam cells formation, collagen fibers were forming in the thickening intima near the lumen (fibrous cap), and denaturing or calcifying gradually far from the lumen, which evolved into various complex plaques. In vitro, myofibroblasts could actively take lots of low-density lipoprotein (LDL) to enhance proliferation. Lots of collagen fibers, foam cells and extracellular lipids accumulation emerged in myofibroblasts cultured with 5% FBS high glucose DMEM without adding modified LDL. It is consistent with the characteristics of human coronary atherosclerotic plaques. It is the first time that lipid rich plaques with lots of foam cells, extracellular lipids and collagen fibers formed in vitro. It demonstrated that myofibroblast should be the direct and main source of collagen fibers, foam cells and extracellular lipids. This suggests that atherosclerosis is not as complicated as previously considered, and it might be mainly a process of myofibroblast remodeling to vascular injury caused by various risk factors. This study made the pathogenesis of atherosclerosis clearer. It would provide a target cell for future treatments of atherosclerotic diseases. In vitro atherosclerotic plaques model formed by human myofibroblasts would be an efficient and convenient way to study atherosclerosis.