BMP Antagonist Gremlin 2 Limits Inflammation After Myocardial Infarction

Area of Science:

• Cardiovascular Biology
• Regenerative Medicine
• Molecular Signaling

Background:

• Gremlin 2 (Grem2), a bone morphogenetic protein (BMP) antagonist, is crucial for early heart development.
• Grem2 expression is upregulated in the adult heart post-myocardial infarction (MI).
• The role of Grem2 and BMP signaling in cardiac repair after injury remains unclear.

Purpose of the Study:

• To elucidate the function of Grem2 in cardiac repair following MI.
• To determine if Grem2 can enhance ventricular function post-injury.

Main Methods:

• Utilized Grem2 loss-of-function (Grem2(-/-)) and gain-of-function (TG(Grem2)) mouse models.
• Administered Grem2 protein intraperitoneally to wild-type mice post-MI.
• Investigated the inflammatory response and BMP signaling pathways in peri-infarct tissues.

Main Results:

• Grem2 is transiently induced in cardiomyocytes during the inflammatory phase post-MI.
• Grem2 deficiency exacerbated inflammation and impaired cardiac function due to excessive BMP signaling.
• Grem2 administration reduced inflammation and improved cardiac function post-MI.
• BMP2 and TNFα synergistically promote inflammation, an effect inhibited by Grem2.

Conclusions:

• Grem2 acts as a molecular barrier, suppressing canonical BMP signaling to control inflammatory cell infiltration after MI.
• This mechanism highlights Grem2's potential in mitigating adverse inflammatory effects and improving cardiac repair.