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Updated: May 27, 2026
Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk
Published on: July 27, 2022
CD36 overexpression predisposes to arrhythmias but reduces infarct size in spontaneously hypertensive rats: gene
Jan Neckář1, Jan Šilhavy, Václav Zídek
1Institute of Physiology, Academy of Sciences of the Czech Republic, Czech Republic.
Insights
The CD36 fatty acid translocase gene variant in spontaneously hypertensive rats increases susceptibility to ischemic ventricular arrhythmias but reduces myocardial infarct size. This suggests CD36 plays a complex role in cardiac response to ischemia.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Genetics
Background:
- CD36 fatty acid translocase is crucial for cardiac energy metabolism, utilizing long-chain fatty acids (FA).
- A naturally occurring Cd36 deletion variant in spontaneously hypertensive rats (SHR) impairs FA transport into cardiomyocytes, leading to cardiac hypertrophy.
- This study investigates the impact of this Cd36 variant on ischemic heart disease outcomes.
Purpose of the Study:
- To determine the effect of wild-type CD36 expression on susceptibility to ischemic ventricular arrhythmias and myocardial infarction in SHR.
- To explore the molecular mechanisms underlying CD36-mediated effects on ischemic tolerance.
Main Methods:
- Utilized an open-chest model of coronary artery occlusion in adult SHR-Cd36 transgenic rats (wild-type Cd36) and age-matched SHR controls.
- Assessed ventricular arrhythmias and myocardial infarct size.
- Performed gene expression profiling using Illumina-based sequencing on left ventricles.
- Investigated the role of catecholamines using reserpine.
Main Results:
- SHR-Cd36 transgenic rats exhibited significantly increased duration and number of ventricular arrhythmias and a higher arrhythmia score compared to SHR controls.
- Conversely, transgenic SHR showed a significantly reduced myocardial infarct size.
- Reserpine abolished the increased susceptibility to arrhythmias in transgenic SHR, indicating involvement of catecholamines.
- Gene expression analysis identified circadian rhythms and oxidative phosphorylation as key KEGG pathways, and circadian rhythms, VDR/RXR activation, IGF1 signaling, and HMGB1 signaling as significant IPA canonical pathways.
Conclusions:
- Transgenic expression of CD36 significantly modulates the incidence and severity of ischemic and reperfusion ventricular arrhythmias and myocardial infarct size in SHR.
- The proarrhythmic effect of the CD36 transgene is dependent on adrenergic stimulation.
- CD36 plays a dual role in ischemic heart disease, promoting arrhythmias while offering protection against infarct expansion.
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 with 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 ± 48 s vs. 55 ± 21 s, P < 0.05), total number of premature ventricular complexes (2,623 ± 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 with 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 hearts, and the increased susceptibility of transgenic SHR to arrhythmias was abolished by reserpine, suggesting the involvement of catecholamines. To further search for possible molecular mechanisms of altered ischemic tolerance, we compared gene expression profiles in left ventricles dissected from 6-wk-old transgenic SHR vs. age-matched controls using Illumina-based sequencing. Circadian rhythms and oxidative phosphorylation were identified as the top KEGG pathways, while circadian rhythms, VDR/RXR activation, IGF1 signaling, and HMGB1 signaling were the top IPA canonical pathways potentially important for Cd36-mediated effects on ischemic tolerance. It can be concluded that transgenic expression of 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 dependent on adrenergic stimulation.
