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Investigation of the myocardial infarction impact regarding high-density lipoprotein effect on endothelial nitric oxide and endothelin-1 production

Grant number: 14/26136-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2015
Effective date (End): February 28, 2019
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Andrei Carvalho Sposito
Grantee:Vitor Wilson de Moura Virginio
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

In myocardial infarction (MI), the intensity of endothelial dysfunction (ED) is an important determinant of morbidity and mortality. Despite ED that follows MI is stongly related to inflammatory activity (IA), little is known about other potential actors. Thus, the action of high-density lipoprotein (HDL) in MI may represent one of the players in this context. In healthy subjects, the HDL is inversely associated with cardiovascular events, mainly to play a protective role of the endothelium. However, in high IA conditions such as MI, HDL loses its anti-atherogenic properties and can induce ED. Our research group showed that systemic AI is increased on the fifth day after MI compared to admission, as well as HDL oxidation. But it is still unclear which are the signaling pathways involved in post-MI HDL dysfunction that explain the reduced bioavailability of nitric oxide (NO). The objective of this project is to evaluate the effect of HDL obtained in the first and fifth day after MI on NO production and endothelin-1 (ET-1) in endothelial cells. We also aim to investigate the major signaling pathways activated in this process, and measure the substrate, cofactors and coenzymes of endothelial NO synthase (eNOS) responsible for the production of NO. The study will include 25 patients admitted in the first 24 after MI and 25 healthy individuals. The HDL will be isolated by ultracentrifugation and cultivated with human coronary artery endothelial cells (HCAEC). The following tests will be used: (I) Immunoblotting to verify the cellular signaling pathways; (II) ELISA to quantify ET-1, inflammatory markers and oxidative stress; (III) Chemiluminescence to mensure NO; (IV) ELISA, and Metabolomics by nuclear magnetic resonance to measure the substrate, cofactors and coenzymes for NO synthesis. (AU)