2020 article
An Essential Protective Role for Cardiomyocyte Alpha1a-adrenergic Receptors in a Mouse Model of Myocardial Infarction
Zhang, J., Ash, T., Huang, W., Smith, A., Huang, H.-Y., & Jensen, B. C. (2020, July 31). CIRCULATION RESEARCH, Vol. 127.
TL;DR:
It is demonstrated that mice deficient of α1A-AR on cardiomyocytes had lower late survival, more profound early pathological injury & adverse mechanical properties after LAD ligation, suggesting that activation ofCardiomyocyte β-ARs plays an essential role in protecting experimental myocadiac infarction, holds the promise of future clinical implications.
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UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: February 8, 2021
Our previous work reveals that dabuzalgron, an oral agonist of alpha-1A adrenergic receptors (α1A-ARs) protects rodents from pathological cardiac stress, a finding in agreement with genetic studies of global α1A-AR overexpression/inactivation. However, it remains largely obscure whether cardiomyocyte-specific actions of α1A-ARs alone determines these cardioprotective effects. To test this essential gap in knowledge, we generated a new mouse line lacking α1A-AR only on cardiomyocytes by crossing αMHC-cre mice with floxed α1A-KO mice (CMKO= cre+ fl/fl, CMWT= cre-fl/fl). After validating specific deletion, baseline features were measured by conscious echo. No overt structural or functional anomaly was identified in either group. Fractional Shortening (FS, %) was virtually identical in 2 groups (51.7±0.7 vs. 52.4±5.3, p=NS). Next, both groups were subjected to permanent left anterior descending (LAD) ligation. By day 14, CMKO had significantly higher mortality (9/15 vs 2/13, p=0.025). To determine early changes that might account for this difference, hearts were harvested at day 3 post-ligation from another cohort. HW did not differ between two groups (7.0±1.1 vs. 7.2±1.1 mg/g·BW, p=NS), neither did LW (8.0±2.1 vs. 7.2±1.0 mg/g·BW, p=NS). Serum troponin level was numerically higher in CMKO mice (8.4±12.4 vs 4.8±6.2 ng/mL,p=0.38). CMKO mice had 51% larger injury (infarcted and leukocyte-infiltrating area) compared to CMWT (31.0±10.5 vs. 20.5±4.9% of LV area, p=0.05). Our preliminary postmortem examination suggested a higher trend of cardiac rupture in injured CMKO (3/5 vs 0/5). To test myocardial biomechanical properties between 2 groups, ventricles from mice 3d post ligation were then subjected to biaxial mechanical stress test. Myocardium from infracted CMKO mice exhibited 70% more stiffness (dt Stress/dt Strain) CMWT (190±34.29 vs.111±42 kPa, p=0.004). Collectively, our results demonstrate that mice deficient of α1A-AR on cardiomyocytes had lower late survival, more profound early pathological injury & adverse mechanical properties after LAD ligation, suggesting that activation of cardiomyocyte α1A-ARs plays an essential role in protecting experimental myocadiac infarction, holds the promise of future clinical implications.