CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Role of Carbonic Anhydrase IX and Hypoxia-Inducible Factor 1 in infarcted rat heart.
FANTINELLI JC; NOLLY MB; MORGAN PE; PINILLA AO
Congreso; ISHR XXI World Congress2016; 2016
Background. Acute myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. MI refers to an oxygen blood perfusion reduction, hypoxia, severely altering cardiac function and myocardial energy metabolism. Studies made on hypoxic tissues of solid tumors revealed an increase expression of Hypoxia-Inducible Factor 1 (HIF-1). This transcription factor translocates to the nucleus, binds to DNA elements and stimulates the transcription of several genes including Carbonic Anhydrase IX (CAIX). During MI the increase expression of HIF-1 reduces infarct size, improving cardiac function. We have previously shown that heart CAIX plays a critical role in regulating myocardial intracellular pH, interacting with bicarbonate transporters (BT). However, the role of CAIX in MI is unknown.Objetive. Our goal is to evaluate CAIX expression in ischemic myocardium and its relation to HIF-1 and BT.Methods. To analyze the role of HIF-1, CAIX and BT in MI we used adult male Wistar rats. MI was produced by permanent ligation of the left anterior descending coronary artery ?in vivo? and analyzed by histology. Heart samples were obtained from infarct, peri-infarct and remote heart regions. Expression of HIF-1, CAIX and BT was analyzed by western blot. Also, interaction of CAIX-BT was assessed by co-immunoprecipitation and colocalization. Results and Conclusions. Infarcted Wistar rats showed a significant increased expression of HIF-1 and CAIX in the peri-infarct regions, compare to the remote heart areas. Peri-infarct regions show a marked physical interaction between CAIX and sodium bicarbonate co-transporter (NBC1). These results suggests that HIF-1 and its downstream target, such us CAIX, interacting with BT may improve cellular pH surroundings and survival mechanisms possibly attenuating progression of cardiac dysfunction after MI.