Abstract
Vascular smooth muscle cells (VSMCs) are central players in carotid atherosclerosis plaque development. Although the precise mechanisms involved in plaque destabilization are not completely understood, it is known that VSMC proliferation and migration participate in plaque stabilization. In this study, we analyzed expression patterns of genes involved in carotid atherosclerosis development (e.g., transcription factors of regulation of SMC genes) of VSMCs located inside or outside the plaque lesion that may give clues about changes in phenotypic plasticity during atherosclerosis. VSMCs were isolated from 39 carotid plaques extracted from symptomatic and asymptomatic patients by endarterectomy. Specific biomarker expression, related with VSMC phenotype, was analyzed by qPCR, western immunoblot, and confocal microscopy. MYH11, CNN1, SRF, MKL2, and CALD1 were significantly underexpressed in VSMCs from plaques compared with VSMCs from a macroscopically intact (MIT) region, while SPP1, KLF4, MAPLC3B, CD68, and LGALS3 were found significantly upregulated in plaque VSMCs versus MIT VSMCs. The gene expression pattern of arterial VSMCs from a healthy donor treated with 7-ketocholesterol showed high similarity with the expression pattern of carotid plaque VSMCs. Our results indicate that VSMCs isolated from plaque show a typical SMC dedifferentiated phenotype with macrophage-like features compared with VSMCs isolated from a MIT region of the carotid artery. Additionally, MYH11, KLF5, and SPP1 expression patterns were found to be associated with symptomatology of human carotid atherosclerosis.
Highlights
Carotid atherosclerosis is a chronic progressive vascular disease which can lead to symptoms such as stroke [1]
Human carotid atherosclerotic plaque tissues obtained by carotid endarterectomy surgery were enzymatically digested and once cells were totally disaggregated from tissue, we routinely analyzed the presence of two specific markers of Vascular smooth muscle cells (VSMCs) i.e., ACTA2 and TAGLN, together with that of endothelial cell marker PECAM1 by flow cytometry in 39 plaque; the center of the lesion (PLQ)-VSMCs and 39 macroscopically intact (MIT)-VSMCs
This study has documented the expression patterns of relevant genes associated with phenotypic modulation in VSMCs by comparing carotid atherosclerotic lesions with macroscopically intact regions located within the surgically excised carotid artery areas
Summary
Carotid atherosclerosis is a chronic progressive vascular disease which can lead to symptoms such as stroke [1]. Unstable carotid atheroma plaques are those that can rupture causing an ischemic attack [2,3], the precise mechanisms underlying plaque destabilization and consequent rupture remain unclear [4]. Vascular smooth muscle cell (VSMC) dedifferentiation is known to play a role in atherosclerosis development [5]. VSMCs found in healthy arteries represent a mature, fully differentiated stage and express the factors needed to ensure their specific contractile features [6]. These cells display high plasticity capacity compared with other muscle cell types [7].
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