GDF5 deficiency prevents cardiac rupture following acute myocardial infarction in mice

Area of Science:

• Cardiovascular Biology
• Regenerative Medicine
• Cardiac Pathophysiology

Background:

• Growth differentiation factor 5 (GDF5) was previously shown to limit infarct expansion post-myocardial infarction (MI).
• The acute role of GDF5 in cardiac rupture following MI remains to be elucidated.

Purpose of the Study:

• To investigate the role of GDF5 in the acute phase of cardiac rupture post-myocardial infarction.
• To determine the impact of GDF5 deficiency on cardiac rupture incidence and survival.

Main Methods:

• Utilized GDF5 knockout and wild-type mice subjected to permanent left anterior descending artery ligation.
• Assessed cardiac rupture incidence, survival rates, heart weight/body weight ratio, infarct size, cardiomyocyte size, and infarct zone gene expression (Col1a1, Col3a1).
• Measured aortic and left ventricular peak systolic pressures, analyzed inflammatory markers, circulating monocytes, and performed bone marrow transplantation (BMT).

Main Results:

• GDF5 deficiency significantly reduced cardiac rupture incidence (4/24 vs. 17/24; P < .05) and improved 28-day survival (79% vs. 25%; P < .0001).
• GDF5-deficient mice exhibited increased myocardial fibrosis (Col1a1, Col3a1 expression) and reduced afterload (lower systolic pressures) at 3-days post-MI.
• Bone marrow transplantation studies suggested a role for tissue-resident GDF5, not bone marrow-derived cells, in cardiac rupture.

Conclusions:

• Loss of GDF5 confers protection against acute cardiac rupture post-MI.
• This protection is associated with enhanced myocardial fibrosis and reduced afterload.
• The protective effects are counterbalanced by chronic adverse cardiac remodeling.