Cardioprotective effect of a monoclonal anti-glycosaminoglycan antibody following transient myocardial ischemia in mice

Myocardial infarction is among the most prominent causes of death worldwide. Following cardiac injury, changes in the composition of the extracellular matrix trigger inflammatory and fibrotic responses. Particularly, left ventricular remodeling and cardiac fibrosis are characterized by pathological glycosaminoglycan (GAG) production and ECM rearrangement, which contribute to cardiomyocyte death and subsequent heart failure. Additionally, chondroitin sulfate-proteoglycans (CS-PGs) accumulation in pathological cardiac remodeling directly bind inflammatory cytokines on the cell membrane and integrate signals contributing to increased collagen biosynthesis, inflammation and fibrotic processes. Previously, we showed that treatment with a chimeric monoclonal antibody (chP3R99 mAb), which recognizes proatherogenic CS-PGs, reduced atherosclerosis in hypercholesterolemic mice and diminished myocardial infarct areas in mice subjected to transient coronary artery ligation. Reduced ischemia–reperfusion damage to the heart was associated with an attenuation of myocardial inflammation. In this proposal, we will determine if the mAb treatment is able to modulate pathological remodeling and enhance cardiac function which would reinforce its cardioprotective effect.

Faculty Supervisor:

Sylvie Marleau

Student:

Partner:

University of Havana

Discipline:

Life Sciences

Sector:

Health and Related Sciences & Technology; Pharmaceuticals; Biotechnology

University:

Université de Montréal

Program: