Abstract 407: Role of Apoa1 in Regulating Mitochondrial Function in Acute Myocardial Infarction
Background: High density lipoprotein (HDL) and apoA-I levels inversely correlate with risk of death from ischemic heart disease; however, the role of apoA-I in myocardial response to ischemia has not been well defined.
Methods and results: To test whether apoA-I, the primary HDL apolipoprotein, has an acute anti-inflammatory role in ischemic heart disease, we induced myocardial infarctions in apoA-I-/- and apoA-1 heterozygotic animals. We observed a 52% increase in infarct size as a percent of area at risk in heterozygotic and a 125% increase in apoA-I null animals compared to wild-type mice. Mitochondrial oxidation contributes to tissue damage in ischemic reperfusion injury, and we found a significant defect in the electron transport chain of cardiac myocytes from apoA-I-/- mice. This was localized to the coenzyme Q pool that impaired electron transfer from complex II to complex III. Administration of CoQ10 to apoA-I null animals normalized the cardiac mitochondrial CoQ pool, and it reduced infarct size to that observed of wild type animals. CoQ10 administration did not significantly alter infarct size in wild-type mice.
Conclusions: These data identify CoQ pool size and impaired mitochondrial function as major contributors to infarct size in the setting of low HDL/apoA-I. These data suggest a previously unappreciated mechanism for myocardial stunning, cardiac dysfunction, and muscle pain associated with low HDL/apoA-I levels that can be corrected by CoQ10 supplementation and suggest populations of patients that may particularly benefit from CoQ10 supplementation.
- © 2012 by American Heart Association, Inc.