Cardiovascular Research - Basic Research Unit in Cardiology
Lino Gonçalves (HUC/IBILI), Pedro Monteiro (HUC/CNC)
The basic research unit in Cardiology has focused its research in diabetes and ischemic cardiomyopathy. We used an animal model of type 2 diabetes, the Goto-Kakisaki rat, fed with an atherogenic diet or submitted to a hypocaloric regime; this animal model was then used to study several anti-diabetic and lipid-lowering drugs (both isolated and in association). This model was used in two different experimental settings: an acute one, with the drugs used only during ischemia-reperfusion, which was induced in the whole heart, later submitted to differential centrifugations to isolate the mitochondrial and citosolic fractions. Several parameters were studied, including mitochondrial swelling, calcium buffering capacity, oxidative stress and caspase cascade activation.

In the other setting, animals were treated with several drugs during four weeks (insulin, metformin, atorvastatin, gliclazida and combinations of these drugs) and then submitted to global ischemia-reperfusion or preconditioning. After this protocol, the same parameters as in the previous setting were evaluated. Before being treated with a drug and again before being sacrificed, blood and urine were taken to measure inflammatory and oxidative stress markers (as well as adipokines), in order to assess their modification by the drugs studied.

We have also used another study protocol, designed to study the cell and molecular biology of the cardiac tissue from hearts explanted from subjects with advanced heart failure and treated with cardiac transplantation.
Besides that, we are continuing our studies with nicorandil, trough cooperation with the University of São Paulo.
PUBLICATIONS
Carreira RS, Monteiro P, Goncalves LM, Providencia LA. 2006, Carvedilol: just another Beta-blocker or a powerful cardioprotector? Cardiovasc Hematol Disord Drug Targets. 6:257-266.
Facundo HT, Carreira RS, de Paula JG, Santos CC, Ferranti R, Laurindo FR, Kowaltowski AJ. 2006, Ischemic preconditioning requires increases in reactive oxygen release independent of mitochondrial K+ channel activity. Free Radic Biol Med. Feb 1;40(3):469-79.
Campos CB, Degasperi GR, Pacifico DS, Alberici LC, Carreira RS, Guimaraes F, Castilho RF, Vercesi AE. 2004, Ibuprofen-induced Walker 256 tumor cell death: cytochrome c release from functional mitochondria and enhancement by calcineurin inhibition. Biochem Pharmacol. Dec 1;68(11):2197-206.
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