Crim۱ inhibits angiotensin II-induced hypertrophy and preserves Kv۴.۲ expression in cardiomyocytes

Objective(s): Angiotensin II (Ang II) plays a key role in the regulation of myocardial hypertrophy via downstream cysteine-rich transmembrane bone morphogenetic protein regulator ۱ (Crim۱). However, it is still unclear whether Crim۱ is involved in ionic channel remodeling. The study aimed to explore the effects of Crim۱ on transient outward potassium current (Ito) and Kv۴.۲ (the main subunit of Ito channel) expression in hypertrophic ventricular cardiomyocytes. Materials and Methods: The ventricular cardiomyocytes were isolated from the neonatal rats. Hypertrophy was induced by Ang II. Crim۱ expression was modulated by using adenovirus transfection. The expression of myosin heavy chain beta (β-MHC), Crim۱, and Kv۴.۲ was determined by RT-qPCR and western blot. The cellular surface area was assessed using Image J software. Ito 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 Crim۱ and Kv۴.۲ and reduced Ito current density. However, Crim۱ overexpression abolished the Ang II-induced hypertrophy and preserved the expression of Kv۴.۲ and Ito current density. Conclusion: Crim۱ overexpression inhibits Ang II-induced hypertrophy and preserves Ito current density via up-regulating Kv۴.۲ in ventricular cardiomyocytes from neonatal rats. Crim۱ could have a role in the development of ventricular arrhythmia in hypertrophic hearts.

Keywords:

Angiotensin II , Cysteine-rich transmembrane , bone morphogenetic protein - regulator ۱ , Ion channel remodeling , Transient outward - potassium current , Ventricular hypertrophy