CTRP1 prevents sepsis-induced cardiomyopathy via Sirt1-dependent pathways

Area of Science:

• Cardiology
• Molecular Biology
• Pathophysiology

Background:

• C1q/tumor necrosis factor-related protein 1 (CTRP1) is a regulator of cardio-metabolic diseases.
• CTRP1 is known to inhibit hypertrophic responses but its role in sepsis-induced cardiomyopathy is unknown.

Purpose of the Study:

• To investigate the role of CTRP1 in sepsis-induced cardiomyopathy.
• To elucidate the underlying molecular mechanisms of CTRP1's effects on cardiac function during sepsis.

Main Methods:

• Cardiomyocyte-specific CTRP1 overexpression using adeno-associated virus in mice.
• Lipopolysaccharide (LPS) injection in CTRP1-overexpressing and CTRP1-deficiency mice.
• In vitro studies using cultured cells and in vivo studies with recombinant CTRP1 infusion.
• Assessment of cardiac function, survival rates, myocardial inflammation, oxidative damage, apoptosis, and Sirtuin 1 (Sirt1) pathway activation.

Main Results:

• CTRP1 overexpression improved survival, cardiac function, and reduced myocardial inflammation, oxidative damage, and apoptosis in LPS-treated mice.
• CTRP1 deficiency exacerbated sepsis-induced cardiac dysfunction and injury.
• CTRP1 protected against LPS-induced cell injury in vitro by activating the Sirt1 signaling pathway.
• Sirt1 inhibition or deficiency abrogated CTRP1-mediated cardioprotective effects.
• Recombinant CTRP1 infusion ameliorated sepsis-induced cardiomyopathy in mice.

Conclusions:

• CTRP1 plays a protective role against sepsis-induced cardiomyopathy.
• CTRP1 exerts its cardioprotective effects via the activation of the Sirt1 signaling pathway.
• CTRP1 represents a potential therapeutic target for managing sepsis-induced cardiac dysfunction.