Award Details:
Award Type: Catalyst
Award #: C-050
Proposal Title: ApoA-I Mediated Regulation of Inflammation and Heart Repair after Heart Attack
PI(s): Godfrey S. Getz (UChicago) and Edward Thorp (NU)
Award Amount: $199,954.00
Application Cycle: Round 16 (Fall 2013)
Award Start Date: March 1, 2014
Award End Date: February 29, 2016
Abstract:
Increased lipids/lipoproteins are a significant risk factor in the progression of heart failure after heart attack/myocardial infarction (MI). Impaired wound healing in the heart is associated with heightened inflammation and reduced ratios of high density lipoprotein (HDL) in the blood. Besides its role during the transport of cholesterol in the circulation, HDL has also been implicated as a regulator of key cellular events during cardiovascular disease. For example, HDL has anti-apoptotic activity, especially in endothelial cells, which is critical during angiogenesis after ischemia. Importantly, HDL levels predict morbidity and mortality after MI in humans. Recent evidence interestingly highlights HDL as a suppressor of immune cell proliferation. This is a revealing insight as mobilization of the immune response directly impacts heart repair. Herein we hypothesize that inflammation resolution and heart repair after heart attack is enhanced by ApoA-I, a significant component of HDL. This will be examined for the first time in an ApoA- I deficient mouse model by measuring cardiac function and immune cell trafficking to the heart after experimental MI. Because of the high clinical occurrence of secondary MIs, we will also examine the influence of ApoA-I on MI-induced enhancement of atherosclerosis, as well as the complementary effect of MI on HDL function. Finally, the therapeutic potential of this pathway will be tested with APOA-I peptide mimetics. Taken together, these studies will lay the ground work to determine for the first time the significance of ApoA-I after heart attack at a physiological level and its therapeutic potential.