High-Density Lipoprotein Treatment Effectively Protected the Endothelial Cells, Mitochondria and Myocardium Against...

This study evaluated whether high-density lipoprotein (HDL) treatment, shown to preserve endothelial cell integrity, could protect the left ventricular ejection fraction (LVEF) in rats from ischemia-reperfusion (IR) injury.

Human umbilical vein endothelial cells (HUVECs) were assigned to six groups: G1 (HUVECs alone); G2 (+healthy-derived oxidized LDL [ox-LDL^H]); G3 (+ox-LDL^H + healthy-derived HDL [HDL^H]); G4 (+acute-coronary-syndrome patient-derived ox-LDL [ox-LDL^P]); G5 (+ox-LDL^P+ HDL^H); and G6 (+ox-LDL^P + patient-derived HDL [HDL^P]). Male Sprague-Dawley rats (n = 54) were divided equally into Group 1 (subcutaneous control), Group 2 (IR only), and Groups 3-6 (IR plus ox-LDL^H, HDL^H, ox-LDL^P, or HDL^P, respectively, implanted into the left ventricular myocardium 3 h after IR).

In vitro, protein and cellular markers of apoptosis, oxidative stress, mitochondrial damage, and MAPK-family signaling were lowest in G1, highest in G4, and significantly lower in G3 than in G2, G5, and G6 (all p < 0.0001); antioxidants and angiogenesis showed the opposite pattern. By day 28, LVEF and LV fractional shortening were highest in Group 1, lowest in Group 5, higher in Group 4 than in Groups 2, 3, and 6, and higher in Group 6 than in Groups 2 and 3 (all p < 0.0001). Inflammation, MAPK cascades, oxidative stress, mitochondrial damage, and LV infarct/fibrotic areas followed the inverse pattern, while antioxidants paralleled LVEF.

HDL^H protected heart function against IR-induced myocardial damage by inhibiting inflammation and oxidative stress and modulating MAPK-family signaling.