Abstract 12170: Increasing HDL Functionality Improved the Survival Rate after Myocardial Infarction
Background: Recently, a high dose of reconstituted (rHDL), apolipoprotein (Apo) A-I Milano, has been shown to significantly reduce the volume of atherosclerotic plaque. Since rHDL is not yet available for clinical use, we newly developed Fukuoka ApoA-I mimetic peptide (FAMP) with 24 amino acids without a phospholipid, which binds to ABCA1 transporter. We examined whether the direct injection of FAMP affected the condition of acute myocardial infarction (MI) in mice.
Method and Results: Eight- to 10-week-old C57Bl/6J male mice were subjected to left anterior coronary artery ligation for 1 week as a model of MI. Control mice were injected intraperitoneally (i.p.) with PBS. FAMP was injected i.p. at 10mg/kg (FAMP-L) or 50mg/kg (FAMP-H). All 3 groups showed a similar degree of LV infarct size. However, the survival rate during the acute phase after MI improved particularly well in the FAMP-H group (8/9, 89%), compared to the FAMP-L (8/11, 73%) and control (7/13, 54%) groups. We then evaluated mRNA expression (eNOS, MCP-1, Gata 4 and p53, etc.) in the heart. The FAMP-L and FAMP-H groups showed significant reductions in MCP-1 mRNA levels. In addition, mRNA levels of some angiogenic compounds (eNOS, Gata 4) were significantly up-regulated by FAMP-L, and a trend was seen in the FAMP-H group. Furthermore, we explored mRNA levels in the heart in the very acute phase of MI. Similarly, the expression levels of anti-inflammatory were suppressed and angiogenic compounds were up-regulated in this acute phase. These results suggested that FAMP might improve the survival rate in the acute phase after MI through HDL-functionality, such as anti-inflammatory and vasculoangiogenic effects in the heart. In addition, capillary isotachoelectrophoresis showed that FAMP attacked circulating HDL, modified the configuration of HDL, and made massive pre-beta HDL, thus improving HDL functionality.
Conclusion: Our newly developed Apo A-I mimetic peptide, FAMP, had beneficial effects in a mouse model of MI. FAMP increased the mRNA levels of some angiogenic compounds and also suppressed the mRNA of inflammatory cytokines, probably through the production of pre-beta HDL. Thus, FAMP may be useful in a new strategy for the prevention of sudden cardiac death after MI.
- © 2012 by American Heart Association, Inc.