P566Effect of Cd36 on cardiac ischemic tolerance and adrenergic signaling in spontaneously hypertensive rats

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Abstract

CD36 fatty acid translocase plays a key role in supplying heart with its major energy substrate, long-chain fatty acids (FA). Previously, we found that the spontaneously hypertensive rat (SHR) harbors a deletion variant of Cd36 gene that results in reduced transport of long-chain FA into cardiomyocytes and predisposes the SHR to cardiac hypertrophy. In the current study, we analyzed the effects of mutant Cd36 on susceptibility to ischemic ventricular arrhythmias and myocardial infarction in adult SHR-Cd36 transgenic rats with wild type Cd36 compared to age-matched SHR controls. Using an open-chest model of coronary artery occlusion, we found that SHR-Cd36 transgenic rats showed profound arrhythmogenesis resulting in significantly increased duration of tachyarrhythmias (207 ± 48s vs. 55 ± 21s, P < 0.05), total number of premature ventricular complexes (2623 ± 517 vs. 849 ± 250, P < 0.05) and arrhythmia score (3.86 ± 0.18 vs. 3.13 ± 0.13, P < 0.001). On the other hand, transgenic SHR compared to SHR controls showed significantly reduced infarct size (52.6 ± 4.3% vs. 72.4 ± 2.9% of area at risk, P < 0.001). Similar differences were observed in isolated perfused rat hearts and the increased susceptibility of transgenic SHR to arrhythmia was abolished by reserpine suggesting the involvement of catecholeamines. Furthermore, forskolin-stimulated activity of adenylyl cyclase was increased in the SHR-Cd36 transgenic strain. It can be concluded that Cd36 plays an important role in modulating the incidence and severity of ischemic and reperfusion ventricular arrhythmias and myocardial infarct size induced by coronary artery occlusion. The proarrhythmic effect of Cd36 transgene appears to be related to increased adrenergic stimulation.

Supported by grants: GAUK 429611, GAAV IAAX01110901, MSM 0021620858

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