HDL in diabetic nephropathy has less effect in endothelial repairing than diabetes without complications

Diabetic nephropathy has a high cardiovascular risk with a low-level HDL(high density lipoprotein) in epidemiologic studies. Glycated HDL in diabetes can diminish the capacity to stimulate endothelial cell migration, but the mechanism has not been adequately explored in diabetic nephropathy. We performed this study to find out whether HDL in diabetic nephropathy is more dysfunctional than HDL in diabetes without complications.

We found that HDL from diabetic nephropathy has a higher level of glycation and induced less cell migration in vitro and in vivo compared with that from diabetes without nephropathy. This finding suggests that diabetic nephropathy has higher levels of glycated HDL and partially explains why patients with DN have a higher risk of cardiovascular disease.

Endothelial cells were treated with N-HDL (normal), D-HDL (T2DM[type 2 diabetes mellitus] without complications), DN-HDL (T2DM nephropathy), N-apoA-I (normal apoA-I), and G-apoA-I (glycated apoA-I in vitro). Cell migration capacity was measured with wound-healing and transwell migration assay in vitro and electric carotid injury model in vivo. Protein glycation levels were measured with nanoLC-MS/MS. PI3K expression and Akt phosphorylation were analyzed by western blot.

In wound-healing assay, DN-HDL showed a 17.12% decrease compared with D-HDL (p < 0.05). DN-HDL showed a 29.85% decrease in comparison with D-HDL (p < 0.001) in transwell assay. In the electric carotid injury model, D-HDL and DN-HDL impaired the re-endothelialization capacity; DN-HDL was less effective than D-HDL. Meanwhile, DN-HDL was found to have a significantly higher protein glycation level than D-HDL (p < 0.001). PI3K expression and Akt phosphorylation were reduced significantly in DN-HDL in comparison with D-HDL and N-HDL. Conclusions: We found that HDL from diabetic nephropathy has a higher level of glycation and induced less cell migration in vitro and in vivo compared with that from diabetes without nephropathy. This finding suggests that diabetic nephropathy has higher levels of glycated HDL and partially explains why patients with DN have a higher risk of cardiovascular disease.