10.3389/fphar.2018.00868.s001 Martin Houde Martin Houde Adel Schwertani Adel Schwertani Hanène Touil Hanène Touil Louisane Desbiens Louisane Desbiens Otman Sarrhini Otman Sarrhini Roger Lecomte Roger Lecomte Martin Lepage Martin Lepage Hugo Gagnon Hugo Gagnon Shinji Takai Shinji Takai Gunnar Pejler Gunnar Pejler Danielle Jacques Danielle Jacques Fernand Gobeil Fernand Gobeil Robert Day Robert Day Pedro D’Orléans-Juste Pedro D’Orléans-Juste Data_Sheet_1_Mouse Mast Cell Protease 4 Deletion Protects Heart Function and Survival After Permanent Myocardial Infarction.pdf Frontiers 2018 chymase mouse mast cell protease 4 myocardial infarction positron emission tomography glycoproteomics active caspase-3 collagen 2018-08-31 04:02:38 Dataset https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_Mouse_Mast_Cell_Protease_4_Deletion_Protects_Heart_Function_and_Survival_After_Permanent_Myocardial_Infarction_pdf/7034069 <p>Chymase, a mast cell serine protease involved in the generation of multiple cardiovascular factors, such as angiotensin II and endothelin-1 (ET-1), is elevated and participates in tissue degeneration after permanent myocardial infarction (PMI). Anesthetized 4-month old male wild-type (WT) C57BL/6J mice and mouse mast cell protease-4 knockout (mMCP-4 KO) congeners were subjected to ligation of the left anterior descending (LAD) coronary artery. A group of mice was then subjected to Kaplan-Meier 28-day survival analysis. In another group of mice, <sup>18</sup>F-fluorodeoxyglucose positron emission tomography (PET) was performed to evaluate heart function and the infarcted zone 3 days post-PMI surgery. Cardiac morphology following PMI was evaluated on formalin-fixed heart slices and glycoproteomic analysis was performed using mass spectrometry. Finally, cardiac and lung tissue content of immunoreactive ET-1 was determined. PMI caused 60% mortality in WT mice, due to left ventricular wall rupture, and 7% in mMCP-4 KO mice. Cardiac PET analysis revealed a significant reduction in left ventricular volume (systolic and diastolic) and preserved the ejection fraction in mMCP-4 KO compared to WT animals. The infarcted area, apoptotic signaling and wall remodeling were significantly decreased in mMCP-4 KO mice compared to their WT congeners, while collagen deposition was increased. Glycoproteomic analysis showed an increase in apolipoprotein A1, an established chymase substrate in mMCP-4 KO mice compared to WT mice post-PMI. ET-1 levels were increased in the lungs of WT, but not mMCP-4 KO mice, 24 h post-PMI. Thus, the genetic deletion of mMCP-4 improved survival and heart function post-PMI.</p>