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Influence of microRNAs in angiogenic and antiangiogenic factors in the pathway of vascular endothelial growth factor in patients with Coronary Artery Disease

Grant number: 17/24605-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2018
Effective date (End): March 31, 2020
Field of knowledge:Health Sciences - Medicine
Principal researcher:Maria Urbana Pinto Brandão Rondon
Grantee:Larissa Ferreira dos Santos
Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated scholarship(s):18/18854-0 - Role of ADAM17 in mediating vascular insulin resistance in type 2 diabetes, BE.EP.DR

Abstract

According to the World Health Organization (WHO), Cardiovascular Disease (CVD) is the leading cause of Death among Chronic Noncommunicable Diseases (DCNT) with 17.7 million global deaths in 2015, which represents 45% of all DCNT deaths. Among CVD, Coronary Artery Disease (CAD) has a high prevalence. The pathophysiology of CAD mainly involves a complex inflammatory atherosclerotic process, increased oxidative stress and platelet and thrombotic activation, leading to endothelial dysfunction, decreased vascular integrity and altered angiogenesis. Thus, patients with CAD suffer a process of vascular remodeling causing a reduction in blood flow, oxygen supply, ischemia and worsening of the patient´s clinical condition. An important mechanism acting on the angiogenic intracellular pathway is the Vascular Endothelial Growth Factor (VEGF) and its receptor VEGFR2. They stimulate the production of eNOS and thereby increase the bioavailability of nitric oxide, the final mediator of angiogenesis. On the other hand, the presence of antiangiogenic factors, such as iNOS and Bad, may alter the cellular integrity and survival since they are directly related to inflammatory and apoptotic processes. In addition, it is known that microRNAs (miRNAs), small sequences of non-protein-encoding RNAs, play an important role in vascular homeostasis by regulating the expression of proangiogenic and antiangiogenic factors. However, the participation of these miRNAs in the modulation of angiogenic and antiangiogenic factors of the VEGF pathway in patients with CAD is still unknown. Therefore, the primary aim of this study is to evaluate the influence of circulating and skeletal muscle microRNAs-126, -16, -21, -21 and -92a on proangiogenic and antiangiogenic factors in the VEGF pathway in patients with CAD. Moreover, we intend to evaluate the gene and protein expression of proangiogenic and cellular survival factors and antiangiogenic, inflammatory and apoptotic factors in patients with CAD, as well as to evaluate the relationship between the microRNAs to be studied and the peripheral blood flow at rest and during exercise. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SANTOS, Larissa Ferreira dos. Influence of microRNAs on angiogenic and antiangiogenic factors in the pathway of vascular endothelial growth factor in coronary artery disease patients. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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