Myeloid-Derived Growth Factor Protects Against Pressure Overload-Induced Heart Failure by Preserving...

Area of Science:

• Cardiology
• Immunology
• Molecular Biology

Background:

• Inflammation plays a complex role in heart failure pathogenesis, with potential beneficial aspects.
• Myeloid-derived growth factor (MYDGF) is secreted by inflammatory cells and aids tissue repair post-myocardial infarction.
• The role of MYDGF in cardiac adaptation to chronic pressure overload remains largely unexplored.

Purpose of the Study:

• To investigate the cellular sources and functional significance of MYDGF in the context of pressure overload-induced heart failure.
• To elucidate the molecular mechanisms by which MYDGF influences cardiac adaptation.
• To assess the therapeutic potential of MYDGF in mitigating heart failure progression.

Main Methods:

• Utilized wild-type, Mydgf-deficient, and transgenic mouse models subjected to transverse aortic constriction for pressure overload.
• Measured MYDGF plasma concentrations using liquid chromatography-mass spectrometry.
• Analyzed MYDGF signaling targets via phosphoproteomics and assessed cardiomyocyte function (Ca2+ transients, contractions).

Main Results:

• MYDGF levels were elevated in pressure-overloaded hearts and plasma, correlating with aortic stenosis severity.
• Mydgf-deficient mice exhibited exacerbated cardiac hypertrophy and dysfunction, while MYDGF overexpression attenuated these effects.
• MYDGF enhanced cardiomyocyte function by upregulating PIM1 and SERCA2a expression, improving calcium handling and contractile performance.

Conclusions:

• MYDGF acts as a crucial adaptive mediator between inflammatory cells and cardiomyocytes, protecting against pressure overload-induced heart failure.
• Restoring MYDGF signaling, either by enhancing its production or through direct administration, shows therapeutic promise for heart failure.
• Targeting the MYDGF-SERCA2a axis represents a novel strategy for treating cardiac dysfunction under persistent stress.