DEDIFFERENTIATION OF VASCULAR SMOOTH MUSCLE CELLS IN THE DEVELOPMENT OF ATHEROSCLEROSIS - THE ROLE OF BMP SIGNALING

• Grant number: 14/16461-0
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): November 01, 2015
• Effective date (End): June 30, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Alexandre Holthausen Campos
• Grantee: Renata Silvério de Barros
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

Atherosclerosis (ATS) is a chronic inflammatory disease of the arterial wall and a major cause of death worldwide. Vascular smooth muscle cells (VSMC) play a crucial role in all stages of atherogenesis. Phenotypic changes in those cells are associated with the progression and instability of atherosclerotic plaque, and the resulting clinical manifestations, such as acute myocardial infarction and stroke. After vascular damage, VSMC synthesize large quantities of extracellular matrix components. Also, they exhibit high rates of proliferation and migration. Bone morphogenetic proteins (BMP) have been associated to different changes during the progression of ATS, such as the induction of vascular calcification and inflammation. Published data (1) from this laboratory demonstrates that BMP-2 and -4, as well as Gremlin, an antagonist of BMP, are upregulated in atherosclerotic lesions in apolipoprotein E-deficient mice fed with hyperlipidemic diet, and in samples from patients with peripheral vascular disease. Of note, primary VSMC overexpress those genes in early stages of ATS, when plaques are not yet detectable by conventional histological analysis. Additionally, we found that Gremlin and BMPs modulate migration of VSMC. However, the full spectrum of BMP pathway's effects on VSMC phenotype and their consequences on ATS remain unknown. This work aims to investigate the role of BMP signaling in the differentiation state of VSMC during atherogenesis in a murine model of the disease. We anticipate that the outcome of the present study will allow a better understanding of the mechanisms involved in the genesis, maintenance and destabilization of atherosclerotic plaques.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE BARROS, RENATA SILVERIO; DIAS, GRAZIELLE SUHETT; DO ROSARIO, ANA PAULA; PALADINO, FERNANDA VIEIRA; LOPES, GABRIEL HERCULANO; CAMPOS, ALEXANDRE HOLTHAUSEN. Gremlin-1 potentiates the dedifferentiation of VSMC in early stages of atherosclerosis. DIFFERENTIATION, v. 109, p. 28-33, SEP-OCT 2019. (14/16461-0)