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Cells 2018, 7(3), 23;

Characterization of Carotid Smooth Muscle Cells during Phenotypic Transition

Neurogenomiks Neuroscience Department, Faculty of Medicine and Nursing, Basque Country University, 48940 Leioa, Spain
ACHUCARRO Basque Center for Neuroscience, Basque Country University, 48940 Leioa, Spain
Neurology Unit, Basurto University Hospital (BUH), 48013 Bilbao, Spain
Vascular Surgery and Angiology Unit, BUH, 48013 Bilbao, Spain
Radiodiagnostic Unit, BUH, 48013 Bilbao, Spain
IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain
Author to whom correspondence should be addressed.
Received: 28 January 2018 / Revised: 2 March 2018 / Accepted: 15 March 2018 / Published: 18 March 2018
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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. View Full-Text
Keywords: carotid atherosclerosis; plaque instability; smooth muscle cells; MYH11 carotid atherosclerosis; plaque instability; smooth muscle cells; MYH11

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Goikuria, H.; Freijo, M.D.M.; Vega Manrique, R.; Sastre, M.; Elizagaray, E.; Lorenzo, A.; Vandenbroeck, K.; Alloza, I. Characterization of Carotid Smooth Muscle Cells during Phenotypic Transition. Cells 2018, 7, 23.

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