Crim1 inhibits angiotensin II-induced hypertrophy and preserves Kv4.2 expression in cardiomyocytes

Jionghong He; Guiling Xia; Long Yang; Zhi Jiang; Ying Yang; Zhaomei Huo; Chuxian Guo

doi:10.22038/IJBMS.2022.61459.13602

Crim1 inhibits angiotensin II-induced hypertrophy and preserves Kv4.2 expression in cardiomyocytes

Iran J Basic Med Sci. 2022 Oct;25(10):1201-1206. doi: 10.22038/IJBMS.2022.61459.13602.

Authors

Jionghong He^{1

2}, Guiling Xia^{1

2}, Long Yang¹, Zhi Jiang¹, Ying Yang¹, Zhaomei Huo¹, Chuxian Guo¹

Affiliations

¹ Department of Cardiology, Guizhou Provincial People's Hospital, Guiyang 550002 China.
² These authors contributed eqully to this work.

Abstract

Objectives: Angiotensin II (Ang II) plays a key role in the regulation of myocardial hypertrophy via downstream cysteine-rich transmembrane bone morphogenetic protein regulator 1 (Crim1). However, it is still unclear whether Crim1 is involved in ionic channel remodeling. The study aimed to explore the effects of Crim1 on transient outward potassium current (Ito) and Kv4.2 (the main subunit of I_to channel) expression in hypertrophic ventricular cardiomyocytes.

Materials and methods: The ventricular cardiomyocytes were isolated from the neonatal rats. Hypertrophy was induced by Ang II. Crim1 expression was modulated by using adenovirus transfection. The expression of myosin heavy chain beta (β-MHC), Crim1, and Kv4.2 was determined by RT-qPCR and western blot. The cellular surface area was assessed using Image J software. I_to was recorded by the whole-cell patch clamp technique.

Results: Ang II-induced hypertrophy in cardiomyocytes was identified by their larger cellular surface area and higher mRNA expression of β-MHC. Ang II significantly decreased the expression of Crim1 and Kv4.2 and reduced I_to current density. However, Crim1 overexpression abolished the Ang II-induced hypertrophy and preserved the expression of Kv4.2 and I_to current density.

Conclusion: Crim1 overexpression inhibits Ang II-induced hypertrophy and preserves I_to current density via up-regulating Kv4.2 in ventricular cardiomyocytes from neonatal rats. Crim1 could have a role in the development of ventricular arrhythmia in hypertrophic hearts.

Keywords: Angiotensin II; Cysteine-rich transmembrane; Ion channel remodeling; Transient outward - potassium current; Ventricular hypertrophy; bone morphogenetic protein - regulator 1.