Endothelial cell apoptosis correlates with low haptoglobin concentrations in diabetes

Abstract

Objective: The haptoglobin 2-2 genotype is associated with lower haptoglobin concentrations and atherosclerosis in diabetes. Endothelial cell apoptosis contributes significantly to atherosclerosis. We studied endothelial cell apoptosis in diabetes patients with haptoglobin 2-2 and non-haptoglobin 2-2 genotype. Approach and results: We pooled plasma from 10 patients with haptoglobin 2-2 and non-haptoglobin 2-2 genotype and quantified endothelial cell apoptosis using a hemodynamic lab-on-chip system. Then, we conducted similar experiments on individual diabetes plasma samples with the haptoglobin 2-2 (n = 20) and non-haptoglobin 2-2 genotype (n = 20). Haptoglobin beta concentrations were measured by Western blot analysis. We looked for association with demographic, metabolic variables, inflammation and oxidative stress. In pooled plasma, endothelial cell apoptosis was higher in haptoglobin 2-2 group (haptoglobin 2-2: 23.18% vs non-haptoglobin 2-2:15.32%). In individual samples, univariate analysis showed that endothelial cell apoptosis correlated with haptoglobin beta concentration [β = -10.29 (95% confidence interval: -13.44, -7.14), p < 0.001] and total haptoglobin concentration [β = -0.03 (95% confidence interval: -0.05, -0.002), p = 0.03]. After multivariable analysis, only haptoglobin beta concentrations remained significant [β = -9.24 (95% confidence interval: -13.10, -5.37), p < 0.001]. The interaction term between haptoglobin genotypes and haptoglobin beta was not significant (p > 0.05). Conclusion: These results show that regardless of the haptoglobin genotype, haptoglobin is associated with prevention of endothelial cell apoptosis in diabetes.