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Protective Role of P62/SQSTM1 on Acute Ischemia‐Induced Arrhythmia Susceptibility
Author(s) -
Hwang Hyun Seok,
Rodriguez Jose,
Koh Yeojung,
Parvatiyar Michelle S.,
Salazar Gloria
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02878
Subject(s) - ischemia , medicine , cardiology , myocyte , intracellular , contraction (grammar) , endocrinology , anesthesia , chemistry , biochemistry
Cardiac ischemia diminishes the intracellular defenses of myocardial cells, resulting in contractile dysfunction, and often leads to ventricular arrhythmias. Recently, we have reported that autophagy adapter protein, p62, modulates the oxidant‐induced cellular Ca handling in myocytes isolated from a mouse with chronic ischemia. Here we investigated the effect of p62 suppression on ventricular arrhythmias after acute ischemia injury in intact heart preparations. Methods Isolated hearts from wild‐type (WT), heterozygote p62 (HET), and homozygote p62 (HOM) mice (n=6–8 per group, both sexes at 10–12 weeks of age) were prepared for global ischemia (15 min steady‐state, 30 min ischemia, and 60 min reperfusion) with electrocardiogram recording. At the end of the experiment, hearts were harvested for biochemical analysis. Results The steady‐state heart rates (HR) were not different among groups. The HR during the reperfusion tended to decrease in HOM hearts (HR, bpm; WT, 322±36, HET, 302±33, HOM, 249±20). The level of p62 protein expression decreased up to 60% in HET hearts compared to WT hearts. The frequency of ventricular arrhythmias reduced in the HET hearts, and further decreased in the HOM hearts during 60 min of reperfusion (Premature ventricular contraction, PVC/min; WT, 2.71±1.16, HET, 0.61±0.18, HOM 0.26±0.10*, * <0.05 vs. WT). The suppression of the p62 gene has a protective effect on acute ischemia‐induced ventricular arrhythmias in intact hearts. Discussion Our results suggest that p62 protein may directly contribute to ventricular arrhythmogenesis via intrinsic beta‐adrenergic signaling in the intact heart after acute ischemia. Support or Funding Information Research Support: Florida State University