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Phenotypic modulation of smooth muscle cells and matrix metalloproteinases as targets for atherosclerotic plaque stabilization

George N. Chaldakov, Maria D. Zhelyazkova-Savova, Daniela Panayotova, Marco Fiore, Stanislav Yanev


Atherosclerosis and its complications, erosion and rupture of the plaque fibrous cap, lead to myocardial infarction and stroke, the main causes of mortality worldwide. In this setting, arterial smooth muscle cells (SMC) of the innermost media undergo phenotypic changes, a switch towards a secretory phenotype engaged in matrix proteins production. In its nature, this is a protective action that forms of a new arterial layer, the fibrous cap covering the plaque thrombogenic lipid core. The risk of plaque rupture is inversely correlated with the presence of secretory state SMC and collagen fibrils within the fibrous cap. Thus, fibrous cap remodeling appears to be the main determinant of plaque vulnerability. Herein, we focus on the potential role of (i) the transcription factors TCF21 and KLF-4 in SMC phenotypic modulation, (ii) the matrix protein secretion of SMC, and (iii) the activity of proteinases (MMP, ADAM, ADAMTS, furin, and the MMP inducer CD147) in this critical process. We argue that focusing on these basic pathways could contribute to the knowledge of fibrous cap stability that might be translated into clinical medicine.


atherosclerosis, fibrous cap, smooth muscle cells, secretion, collagen, matrix metalloproteinases, TCF21, KLF-4, furin, CD147

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About The Authors

George N. Chaldakov
Department of Anatomy and Cell Biology, Faculty of Medicine, Medical University of Varna

Maria D. Zhelyazkova-Savova
Department of Pharmacology and Clinical Pharmacology and Therapeutics, Faculty of Medicine, Medical University of Varna

Daniela Panayotova
Department of Cardiac Surgery, St Marina University Hospital, Varna

Marco Fiore
Institute of Biochemistry and Cell Biology, Section of Neurobiology, National Research Council (CNR), Rome

Stanislav Yanev
Laboratory of Drug Toxicology, Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia

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