Inhibition of acid sphingomyelinase activity ameliorates endothelial dysfunction in db/db mice.

Inhibition of acid sphingomyelinase activity ameliorates endothelial dysfunction in db/db mice. Biosci Rep. 2019 Mar 25;: Authors: Jiang M, Huang S, Duan W, Liu Q, Lei M Abstract Acid sphingomyelinase (aSMase) plays an important role in endothelial dysfunction. Here, we show that elevated aSMase activity and ceramide content were reduced by desipramine treatment in diabetic animals. The inhibitor of aSMase, desipramine, improved vascular dysfunction in db/db mice. High glucose-induced upregulation of aSMase activity and ceramide levels were restored by treatment with aSMase siRNA or desipramine in endothelial cells. In addition, aSMase siRNA or desipramine treatment increased the release of nitric oxide (NO) and the phosphorylation of endothelial NO synthase (eNOS) in diabetic mouse aortas and aortic endothelial cells with high glucose. These results indicate that inhibition of aSMase/ceramide pathway improves endothelium-dependent vascular relaxation (EDR) largely through regulating the eNOS/NO pathway in diabetic animals. PMID: 30910852 [PubMed - as supplied by publisher]
Source: Bioscience Reports - Category: Biomedical Science Authors: Tags: Biosci Rep Source Type: research