Rosiglitazone exacerbates the recovery of diminished Ca2+ transient amplitude in cardiomyocytes from metabolic syndrome rats

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 776-795-Cardiometabolic Risk & Vascular Biology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-781
Gaudencio Fernandez Miranda*1, Martha Mercado Morales1, Mavil Lopez Casamichana2 and Angelica Rueda1
1Cinvestav-IPN, Mexico, Mexico, 2UACM, México City, Mexico, Mexico
The Metabolic Syndrome (MS) is a multi-pathological disorder that directly promotes the development of cardiovascular diseases. However, the molecular mechanisms responsible for the cardiovascular complications in MS are unclear and could be related to anomalies in the activity and/or expression of cardiac Ca2+ handling proteins, such as the cardiac Ryanodine Receptor (RyR2) and the Sarco/Endoplasmic Reticulum Ca2+ pump (SERCA pump).  Since, Rosiglitazone, a potent and highly selective agonist of the peroxisome proliferator-activated receptor-gamma (PPARg) recovers activity and expression level of SERCA pump in platelets of diabetic patients, our aim was to examine the effect of acute (100 mM, 5 min) and chronic (0.5 mg/Kg, 4 weeks) administration of Rosiglitazone in the activity and expression level of RyR2 and SERCA pump in heart tissue and isolated cardiomyocytes of an experimental model of MS in rat. MS was induced by administration of sucrose (30% in the drinking water) for 24 weeks. Fluo-3 loaded cardiomyocytes were used to evaluate in-cell RyR2 spontaneous activity (Ca2+ sparks) by confocal microscopy. In addition, we evaluated the expression of RyR2 and SERCA pump by qPCR. We found that relative mRNA levels of both proteins showed a tendency to decrease in animals developing MS, although this trend was not significant. Rosiglitazone superfusion onto Fluo-3-loaded cardiomyocytes diminished Ca2+ spark frequency in MS cardiomyocytes with no modification of their amplitude, duration and time-to-peak. However, in chronic treatment, Rosiglitazone not only restored but exacerbated the recovery of Ca2+ transient amplitude in intact cardiomyocytes of Metabolic Syndrome animals; which could help to explain the high incidence of heart attack events in diabetic patients under Rosiglitazone treatment. Funding ICyTDF Project No. 331/2010.

Nothing to Disclose: GF, MM, ML, AR

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