Full Record

New Search | Similar Records

Title HDL 3B e 3C reduzem a lesão de isquemia e reperfusão e preservam a função sistólica do ventrículo esquerdo após infarto do miocárdio por mecanismo mediado pelo óxido nítrico   : HDL 3B and 3C reduce ischemia and reperfusion injury and preserve the systolic function of the left ventricle after myocardial infarction by a mechanism dependent on nitric oxide  : HDL 3B and 3C reduce ischemia and reperfusion injury and preserve the systolic function of the left ventricle after myocardial infarction by a mechanism dependent on nitric oxide  
Publication Date
Date Accessioned
University/Publisher Universidade Estadual de Campinas
Abstract Abstract: The pandemic of ischemic heart disease mainly manifested in the form of myocardial infarction (MI) is associated with a high mortality and morbidity rate in the world population. During MI, even with rapid intervention to restore coronary flow, about half the size of the remaining lesion is due to ischemia and reperfusion (I/R) injury. Several therapeutic strategies have been studied to reduce the damage caused by I/R injury, however, no effective therapy has been demonstrated. Based on the cardioprotective effects of high-density lipoprotein (HDL) particles such as anti-inflammatory, antioxidant, antiapoptotic activity, as well as its important regulation on vascular homeostasis, make HDL a potential candidate for attenuation I/R injury. HDL particles can be divided into five subclasses: 2B and 2A (larger and rich in lipids), 3A, 3B and 3C (smaller and rich in proteins). However, it is not clear until now which HDL subclass would yield the most benefits in the I/R injury. The aim of this study was to evaluate which HDL subclass could result in greater protection after MI, in relation to infarct size, left ventricular (LV) systolic function, and coronary flow. Similarly, we sought to evaluate the role of nitric oxide (NO) synthesis, as well as to explore the cell pathways directly involved in the protection triggered by HDL/NO and mitochondrial protection. The present hypothesis was verified with total and subclass HDL samples isolated from 15 healthy volunteers (26 ± 5 years old). HDL was tested in an I/R model in hearts isolated from Wistar rats perfused in the Langendorff system. The hearts were submitted to 35 minutes of ischemia and 90 minutes of regional myocardial reperfusion. The HDL was infused at very first minutes of reperfusion. The same approach was tested in vitro separately on endothelial and cardiomyocytes cells in the hypoxia-reoxygenation scenario. NO biosynthesis was evaluated ex vivo and in vitro by chemiluminescence, and cardioprotection pathways were evidenced by immunoblotting. Mitochondrial respiration was characterized by the rate of oxygen uptake Our results demonstrated that total HDL was able to decrease -24% (p<0.01) infarct size and improve systolic function during reperfusion. We found that the smallest HDL, subclasses 3C and 3B, were more efficient in reducing infarct size (-30%, p<0.001; -25%, p<0.01, respectively) and increasing viability of cardiomyocytes (three times; p=0.023) in the hypoxia-reoxygenation scenario. HDL 3C and 3B also improved LV systolic function during reperfusion and reduced coronary resistance compared to control and other subclasses. In addition, we have shown that NO plays a key role in cardioprotection after ischemia and that the HDL 3C and 3B were the most effective phenotypes in stimulating increased NO bioavailability in coronary effluent (240%, p<0.0001 and 204%, p<0.0001), in the extracellular environment of human coronary endothelial cells (330%, p<0.0001) and cardiomyocytes (390%, p<0.0001). In endothelial cells, this NO increase by…
Subjects/Keywords Lipoproteinas HDL; Infarto do miocárdio; Cardioproteção; Isquemia miocárdica; Reperfusão miocárdica; Óxido nítrico; Respiração mitocondrial; Lipoproteins, HDL; Myocardial infarction; Cardioprotection; Myocardial ischemia; Myocardial reperfusion; Nitric oxide; Mitochondrial respiration
Contributors UNIVERSIDADE ESTADUAL DE CAMPINAS (CRUESP); Sposito, Andrei Carvalho, 1967- (advisor); Universidade Estadual de Campinas. Faculdade de Ciências Médicas (institution); Programa de Pós-Graduação em Clínica Médica (nameofprogram); Velloso, Licio Augusto (committee member); Rached, Fabiana Hanna (committee member); Passarelli, Marisa (committee member); Oliveira, Rodrigo Bueno de (committee member)
Language português
Country of Publication br
Record ID oai:repositorio.unicamp.br:REPOSIP/335311
Repository unicamp
Date Indexed 2020-09-09
Issued Date 2019-01-01 00:00:00
Note [] Orientador: Andrei Carvalho Sposito; [] Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas; [degreelevel] Doutorado; [degreediscipline] Clinica Medica; [degreename] Doutor em Ciências; [sponsordocumentnumber] 2014/26136-9; [sponsordocumentnumber] 1501479; [sponsor] FAPESP; [sponsor] CAPES;

Sample Images