salvianolic-acid-B and Diabetic-Angiopathies

This study investigated the roles of bone morphogenetic protein-4 (BMP4) and ROS in diabetic endothelial dysfunction and explored whether Salvianolic acid B (Sal B) improved endothelial function by affecting BMP4-ROS in diabetic mice.. db/db mice were orally administrated with Sal B (10 mg/kg/day) for one week while db/m + mice were injected with adenoviral vectors delivering BMP4 (3 × 10. We first revealed the existence of a BMP4-ROS cycle in db/db mice, which stimulated p38 MAPK/JNK/caspase 3 and thus participated in endothelial dysfunction. One week-treatment or 24 h-incubation with Sal B disrupted the cycle, suppressed p38 MAPK/JNK/caspase 3 cascade, and improved endothelium-dependent relaxations (EDRs) in db/db mouse aortas. Importantly, in vivo Sal B treatment also improved flow-mediated dilatation in db/db mouse second order mesenteric arteries. Furthermore, in vivo BMP4 overexpression induced oxidative stress, stimulated p38 MAPK/JNK/caspase 3, and impaired EDRs in db/m + mouse aortas, which were all reversed by Sal B.. The present study demonstrates that Sal B ameliorates endothelial dysfunction through breaking the BMP4-ROS cycle and subsequently inhibiting p38 MAPK/JNK/caspase 3 in diabetic mice and provides evidence for the additional new mechanism underlying the benefit of Sal B against diabetic vasculopathy.

Topics: Animals; Aorta; Benzofurans; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins; Caspase 3; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Disease Models, Animal; Endothelial Cells; Endothelium, Vascular; Male; MAP Kinase Signaling System; Mesenteric Arteries; Mice; Mice, Inbred C57BL; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Reactive Oxygen Species; Vascular Diseases; Vasodilation