Celecoxib modulates hypertrophic signalling and prevents load-induced cardiac dysfunction

Area of Science:

• Cardiovascular Research
• Molecular Cardiology
• Pharmacology

Background:

• Cardiac hypertrophy progresses to heart failure, associated with increased Akt phosphorylation.
• Celecoxib, a COX-2 inhibitor, inhibits Akt signaling in non-myocardial tissues.
• The effect of celecoxib on myocardial Akt signaling and hypertrophy is not well understood.

Purpose of the Study:

• To investigate the effects of celecoxib on Akt signaling and cardiac hypertrophy in the myocardium.
• To determine if celecoxib can attenuate cardiac hypertrophy and dysfunction in vivo.

Main Methods:

• Studied celecoxib's effects on Akt signaling, protein synthesis, and BNP mRNA in rabbit cardiac myocytes.
• Administered celecoxib to mice with pressure overload induced by aortic banding.
• Assessed left ventricular dilation, contractile function, and mortality in treated and placebo groups.

Main Results:

• Celecoxib inhibited insulin-induced Akt phosphorylation and downstream targets (GSK-3beta, p70 S6 kinase) in cardiac myocytes by reducing PTEN phosphorylation.
• Celecoxib suppressed agonist-induced protein synthesis and BNP mRNA expression, key markers of hypertrophy.
• In vivo, celecoxib attenuated left ventricular dilation, improved contractile function, and reduced mortality in pressure-overloaded mice.

Conclusions:

• Celecoxib effectively modulates Akt signaling and hypertrophic responses in the myocardium.
• This agent reduces load-induced cardiac remodeling, dysfunction, and mortality.
• Celecoxib holds potential for preventing and treating maladaptive hypertrophy and heart failure progression.