Pleiotropic Effects of Improved Apoprotein A-I Mimetic Peptide

Background: To prevent the onset and progression of atherosclerotic cardiovascular disease, we previously synthesized a mimetic peptide of apolipoprotein A-I (Fukuoka University ApoA-I Mimetic Peptide (FAMP)), which is a major component of high-density lipoprotein (HDL). We reported that FAMP enhanced HDL-induced endothelial tube formation to help counteract cardiac muscle ischemia, and had anti-inflammatory effects or an effect on cholesterol efflux capacity to prevent coronary atherosclerosis. Methods: We have now synthesized an improved FAMP (i-FAMP) and examined whether its effects are stronger than those of conventional FAMP. First, human coronary artery endothelial cells (HCECs) were used to measure the tube-forming effects of these peptides. In addition, as an anti-inflammatory effect, we also investigated their inhibitory effects on the secretion of monocyte chemotactic protein-1 (MCP-1) from cells. As an anti-apoptotic effect to prevent cardiac muscle ischemia, the inhibitory effect on caspase-3/7 activation was also measured in H9C2 rat cardiomyocyte cells. Results: HDL promoted HCEC tube formation and suppressed MCP-1 secretion from HCECs and caspase-3/7 activation in H9C2 cells. The tube formation under HDL with i-FAMP treatment was stronger than that under HDL with FAMP. HDL in the presence of FAMP or i-FAMP significantly suppressed MCP-1 secretion compared to HDL in the absence of FAMP or i-FAMP, whereas there were no significant changes in MCP-1 secretion between HDL with FAMP and HDL with i-FAMP treatment. HDL with i-FAMP and FAMP did not enhance the suppression of caspase-3/7 activation by HDL. Conclusions: HDL affected HCEC tube formation and had anti-inflammatory and anti-apoptotic effects; i-FAMP may or may not enhance these actions. In some cases, these effects were stronger than those of conventional FAMP. Cell Mol Med Res. 2023;1(2):44-50 doi: https://doi.org/10.14740/cmmr53