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Molecular mechanisms of vascular smooth muscle cell trans-differentiation and calcification in atherosclerosis

Monika Roszkowska 1
1 MEM² - Métabolisme, Enzymes et Mécanismes Moléculaires
ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
Abstract : Vascular calcification (VC) is a hallmark of atherosclerosis plaques. Calcification (formation of apatite) of advanced lesions share common features with endochondral ossification of long bones and appears to stabilize plaques. This process is associated with trans-differentiation of vascular smooth muscle cells (VSMCs) into chondrocyte-like cells. On the other hand, microcalcification of early plaques, which is poorly understood, is thought to be harmful. The two proteins necessary for physiological mineralization are tissue-nonspecific alkaline phosphatase (TNAP) and collagen. Under pathological conditions, TNAP is activated by inflammatory cytokines in VSMCs, whereas collagen is produced constantly. The activation of TNAP appears to induce calcification of these cells. Therefore, the objective of this PhD thesis was to study the role of TNAP and generated apatite crystals in the VSMC trans-differentiation and determine underlying molecular mechanisms. Based on the obtained results, we propose that activation of BMP-2, a strong inducer of ectopic calcification, and formation of apatite crystals generated by TNAP represents a likely mechanism responsible for stimulation of VSMC trans-differentiation. Moreover, we were interested in localization and function of mineralization markers such as TNAP and annexins in mineralization process mediated by trans-differentiated VSMCs and VSMC-derived matrix vesicles (MVs). We observed that, similarly as in the case of typical mineralizing cells, increased TNAP activity in VSMC-derived MVs and association with collagen were important for their ability to mineralize
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Submitted on : Monday, September 24, 2018 - 7:10:07 PM
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Monika Roszkowska. Molecular mechanisms of vascular smooth muscle cell trans-differentiation and calcification in atherosclerosis. Biochemistry, Molecular Biology. Université de Lyon; Instytut biologii doświadczalnej im. M. Nenckiego (Pologne), 2018. English. ⟨NNT : 2018LYSE1059⟩. ⟨tel-01880436⟩



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