Bone Morphogenetic Protein 9 Protects Against Myocardial Infarction by Improving Lymphatic Drainage Function and...

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cytokine Signaling

Background:

• Bone morphogenetic protein 9 (BMP9), a transforming growth factor-β (TGF-β) family member, influences glucose metabolism, fibrosis, and lymphatic development.
• The specific role of BMP9 in the context of myocardial infarction (MI) has not been previously elucidated.

Purpose of the Study:

• To investigate the expression and function of BMP9 in myocardial infarction (MI).
• To determine the therapeutic potential of BMP9 in mitigating MI-induced cardiac damage.

Main Methods:

• Quantification of BMP9 levels in cardiac tissues and plasma from human and mouse MI models using immunoassay and immunoblot.
• Assessment of BMP9's role in MI by studying BMP9-deficient mice and evaluating the effects of BMP9 replenishment via adeno-associated virus (AAV) vectors or recombinant protein.
• Investigation of the downstream effects of BMP9 on lymphatic drainage, cardiac edema, and mitochondrial 2,4-dienoyl-CoA reductase 1 (DECR1) expression and function.

Main Results:

• Circulating and cardiac BMP9 levels are significantly elevated in MI patients and mice, correlating negatively with cardiac function.
• BMP9 deficiency exacerbates left ventricular dysfunction, infarct size, and cardiac fibrosis post-MI.
• BMP9 replenishment attenuates MI-induced cardiac damage by enhancing lymphatic drainage, reducing edema, and upregulating mitochondrial DECR1, which improves cardiac bioenergetics and protects cardiomyocytes.
• DECR1 is essential for BMP9's protective effects against MI-induced cardiomyopathy.

Conclusions:

• BMP9 plays a protective role in myocardial infarction (MI).
• BMP9 mitigates cardiac damage by enhancing lymphatic function and promoting mitochondrial bioenergetics via DECR1.
• BMP9's protective effects involve intricate cross-talk between the liver, lymphatic system, and heart.