Anti-apoptotic Effects of a Calpain Inhibitor on Cardiomyocytes in a Canine Rapid Atrial Fibrillation Model

Abstract

The calpain inhibitor N-Acetyl-Leu-Leu-Met attenuated apoptosis through a complicated network of apoptosis-related proteins, which may result in improvement of structural remodeling in atrial fibrillation.

CASP3 genetic variants and susceptibility to atrial fibrillation in Chinese Han population

“…The results are consistent with the notion that caspase-3 plays an important role in the pathogenesis of atrial structural remodeling during AF [15][16][17][18][19][20]. Future research is needed to confirm the present findings, by replicating this association in independent populations of various ethnic origins, especially in large-scale prospective cohort studies.…”

“…Compared to tissues of patients in sinus rhythm, fibrillating atria have significantly increased caspase-3 expression [15, 16]. Increased expression of caspase-3 also has been detected in canine fibrillation atria in both burst atrial pacing model and ventricular tachypacing model [17][18][19]. Spironolactone treatment reversed the increased expression of caspase-3 in canine atrial myocytes induced by chronic atrial pacing, and prevented the increased inducibility and duration of AF induced by tachypacing [19].…”

“…Caspase-3 is one of the effecter caspases that plays a central role in apoptosis. Several studies have shown that increased expression of caspase-3 has been detected in human and canine fibrillating atria [15][16][17][18][19]. Genetic suppression of atrial caspase-3 protein expression resulted in the suppression of AF-associated apoptosis in a porcine AF model [20].…”

Calpain in Atrial Fibrillation: Friend or Foe?

“…The present study by Yue Li et al [6] shows that an inhibitor of calpain I (N-Acetyl-Leu-Leu-Met; ALLM) diminishes the extent of apoptotic cell death in an in vivo canine model of AF. They show that inhibition of calpain I is able to reduce the rate of apoptosis (apoptosis index) and caspase expression as otherwise found highly increased after the 3 week period of atrial pacing.…”

Improving Atrial Fibrillation Therapy

“…In a canine model of AF, apoptosis associated with the arrhythmia was also associated with increased activity of calpain, an intracellular calcium-activated protease, and caspase-3, an apoptotic enzyme (46). With this basis for target selection, genetic knockdown of caspase-3 with an adenovirus-mediated silencing RNA in a porcine model of AF resulted in prolonged atrial conduction and delayed onset of AF with atrial burst pacing (28).…”