CTRP1 Aggravates Cardiac Dysfunction Post Myocardial Infarction by Modulating TLR4 in Macrophages

Area of Science:

• Cardiovascular Biology
• Immunology
• Metabolic Disease Research

Background:

• C1q/TNF-α-related protein 1 (CTRP1), an adiponectin paralog, is linked to diabetes and cardiovascular disease.
• The specific role of CTRP1 in cardiac function following myocardial infarction (MI) remains largely unknown.

Purpose of the Study:

• To investigate the impact of CTRP1 on cardiac performance and cellular responses in a mouse model of myocardial infarction.
• To elucidate the underlying mechanisms by which CTRP1 influences cardiac recovery and inflammation post-MI.

Main Methods:

• CTRP1 global knockout mice and wild-type mice treated with recombinant CTRP1 were subjected to myocardial infarction (MI) induction.
• Macrophage activation, inflammation, oxidative stress, and cardiac function were assessed post-MI.
• The role of Toll-like receptor 4 (TLR4) and adiponectin receptor 1 in CTRP1-mediated effects was examined.

Main Results:

• CTRP1 deficiency improved survival, reduced infarct size, and enhanced cardiac function post-MI.
• CTRP1 administration worsened cardiac conditions, increased inflammation, and elevated oxidative stress.
• CTRP1 promoted macrophage activation via adiponectin receptor 1 and TLR4, exacerbating cardiac dysfunction.

Conclusions:

• CTRP1 suppresses cardiac function post-MI, primarily through the activation of macrophages via the TLR4 pathway.
• Targeting CTRP1 presents a potential therapeutic strategy for mitigating cardiac dysfunction and improving outcomes after myocardial infarction.