Mouse Mast Cell Protease 4 Deletion Protects Heart Function and Survival After Permanent Myocardial Infarction

Area of Science:

• Cardiovascular Research
• Protease Biology
• Myocardial Infarction

Background:

• Chymase, a mast cell serine protease, contributes to cardiovascular disease by generating factors like angiotensin II and endothelin-1 (ET-1).
• Elevated chymase levels and activity are implicated in tissue degeneration following myocardial infarction (PMI).

Purpose of the Study:

• To investigate the role of mouse mast cell protease-4 (mMCP-4) in cardiac remodeling and survival after permanent myocardial infarction (PMI).
• To evaluate the impact of mMCP-4 genetic deletion on heart function, infarct size, and associated molecular changes post-PMI.

Main Methods:

• Permanent myocardial infarction (PMI) was induced in wild-type (WT) and mMCP-4 knockout (mMCP-4 KO) mice.
• Survival analysis, cardiac ¹⁸F-fluorodeoxyglucose positron emission tomography (PET), morphological evaluation, glycoproteomic analysis, and ET-1 quantification were performed.

Main Results:

• mMCP-4 KO mice exhibited significantly improved 28-day survival (93%) compared to WT mice (40%) post-PMI, with reduced left ventricular rupture.
• Cardiac PET revealed preserved ejection fraction and reduced left ventricular volume in mMCP-4 KO mice.
• mMCP-4 deletion decreased infarct size, apoptotic signaling, and cardiac remodeling, while increasing collagen deposition and apolipoprotein A1 levels.

Conclusions:

• Genetic deletion of mMCP-4 significantly enhances survival and preserves cardiac function after myocardial infarction.
• mMCP-4 plays a critical role in the detrimental processes of cardiac degeneration and adverse remodeling following PMI.