Activation of thromboxane A2 receptors mediates endothelial dysfunction in diabetic mice

Clinical and Experimental Hypertension : CHE
Xiaona XieNing Liu

Abstract

Diabetes is one of high-risk factors for cardiovascular disease. Improvement of endothelial dysfunction in diabetes reduces vascular complications. However, the underlying mechanism needs to be uncovered. This study was conducted to elucidate whether and how thromboxane A2 receptor (TPr) activation contributes to endothelial dysfunction in diabetes. Exposure of human umbilical vein endothelial cells (HUVECs) to either TPr agonists, two structurally related thromboxane A2 (TxA2) mimetics, significantly reduced phosphorylations of endothelial nitric oxide synthase (eNOS) at Ser1177 and Akt at Ser473. These effects were abolished by pharmacological or genetic inhibitors of TPr. TPr-induced suppression of eNOS and Akt phosphorylation was accompanied by upregulation of PTEN (phosphatase and tension homolog deleted on chromosome 10) and Ser380/Thr382/383 PTEN phosphorylation. PTEN-specific siRNA restored Akt-eNOS signaling in the face of TPr activation. The small GTPase, Rho, was also activated by TPr stimulation, and pretreatment of HUVECs with Y27632, a Rho-associated kinase (ROCK) inhibitor, rescued TPr-impaired Akt-eNOS signaling. In mice, streptozotocin-induced diabetes was associated with aortic PTEN upregulation, PTEN-Ser380/T...Continue Reading

References

Mar 24, 1999·The Journal of Cell Biology·C D Nobes, A Hall
Aug 15, 2000·Journal of Cardiovascular Pharmacology·M J MihmJ A Bauer
Apr 19, 2005·Nature Medicine·Koji TakayamaFumitaka Ushikubi
Feb 7, 2006·Cardiovascular Research·Arántzazu AlfrancaJuan Miguel Redondo
Aug 23, 2008·Nature Reviews. Molecular Cell Biology·Sarah J Heasman, Anne J Ridley
Mar 2, 2013·Current Pharmaceutical Design·Teresa Vanessa FiorentinoFranco Folli
Jan 1, 2014·The Review of Diabetic Studies : RDS·Sandra J Hamilton, Gerald F Watts
May 2, 2014·Current Atherosclerosis Reports·Francesco PaneniFrancesco Cosentino
Jan 8, 2015·Journal of Exercise Nutrition & Biochemistry·Moon-Hyon Hwang, Sangho Kim
Jul 16, 2015·Journal of Cellular and Molecular Medicine·Jie WangShuang-Xi Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Cardiovascular Disorder in Diabetes

Diabetes is associated with an increased risk of cardiovascular disorders and heart failure. Discover the latest research here.