Abstract 239: Endothelial Injury- Repair Disequilibrium with Excess Cholesterol Milieu is Linked with Increased Endothelial Cells Apoptosis in Contrast to Decreased Circulating Endothelial Progenitors Clonogenic Potential.
Background: Circulating detached endothelial cells (CEC) and microparticles (EMP) mirror endothelial injury. EMP antigenic phenotype differentiates endothelial cell (EC) apoptosis against activation. Meanwhile, EC repair is linked to circulating endothelial progenitors (CEPC). With multiple cardiac risk factors, high CEC, EMP unlike low CEPC levels were observed. Nevertheless, the independent effect of high cholesterol (HC) with elevated low-density lipoprotein (LDL) compared to normal cholesterol (NC) on EC injury-repair was not explored.
Methods: HC single risk factor, control subjects were studied. Flow cytometry with human anti-CD31, 42b; 62E identified EMP respectively anti-CD 146, CD 45 for CEC. HC, NC group derived CEPC underwent colony formation assay (CFU). Acquired coronary artery endothelial cells (CAEC), CEPC from NC subjects were cultured with plasma from each group (p<0.05 significant).
Results: Circulating CEC CD 146+/45−, EMP CD31+/42b- were increased in HC subjects (each p=0.001) unlike CD 62E+ (p>0.05). HC induced CAEC in vitro CD 31+/42b-release (p=0.01) but not CD 62E+ (p>0.05). Cholesterol, LDL levels positively correlated with CD 31+/42b− in vivo. CEPC CFU level was lower from HC then NC patients (p>0.001). CEPC relation with HC was negative, likewise with EMP counts. NC subjects derived CEPC CFU generation was reduced by HC compared to NC plasma (12±4; 25±4 p<0.002).
Conclusion: CEC, EMP increased levels reflect exaggerated endothelial injury with HC. Low CEPC infer diminished repair. Elevated EMP count demonstrates a negative correlation with decreased CEPC level. Induced and circulating distinct EMP phenotype suggests EC apoptosis with HC, rather then activation at this stage. HC also demonstrates the capacity to decreasing CEPC functionality by altering the clonogenic potential. Therefore, HC milieu in humans, independently and at early stages, damages the endothelial injury-repair process homeostatic equilibrium.