Adiponectin as a Link Between Type 2 Diabetes and Vascular NADPH Oxidase Activity in the Human Arterial Wall: The Regulatory Role of Perivascular Adipose Tissue

• DOI: 10.2337/db14-1011
• Publication Date: 2015-01-01T05:08:31Z
• Authors: Alexios S. Antono...; Marios Margaritis; Patricia Coutinho; Cheerag Shirodaria; Costas Psarros; Laura Herdman; Fabio Sanna; Ravi De Silva; Mario Petrou; Rana Sayeed; George Krasopoulos; Regent Lee; Janet Digby; Svetlana Reilly; Constantinos Bako...; Dimitris Tousoulis; Benedikt Kessler; Barbara Casadei; Keith M. Channon; Charalambos Anton...
• Keywords: NOX4

Oxidative stress plays a critical role in the vascular complications of type 2 diabetes. We examined effect diabetes on NADPH oxidase human vessels and explored mechanisms this interaction. Segments internal mammary arteries (IMAs) with their perivascular adipose tissue (PVAT) thoracic were obtained from 386 patients undergoing coronary bypass surgery (127 diabetes). Type was strongly correlated hypoadiponectinemia increased oxidase–derived superoxide anions (O2˙−). The genetic variability ADIPOQ gene circulating adiponectin (but not interleukin-6) independent predictors O2˙−. However, expression PVAT positively Recombinant directly inhibited ex vivo by preventing activation/membrane translocation Rac1 downregulating p22phox through phosphoinositide 3-kinase/Akt-mediated mechanism. In coincubation models IMA/PVAT, activation arterial triggered peroxisome proliferator–activated receptor-γ–mediated upregulation neighboring via release oxidation products. demonstrate for first time humans that reduced levels individuals stimulates oxidase, while “senses” activity underlying vessel responds upregulating expression. This PVAT-vessel interaction is identified as novel therapeutic target prevention