The defective protein level of myosin light chain phosphatase (MLCP) in the isolated saphenous vein, as a vascular conduit in coronary artery bypass grafting (CABG), harvested from patients with diabetes mellitus (DM)

• Published in: Biochemical and biophysical research communications 2011-08, Vol.412 (2), p.323-327
• Main Authors: Matsuo, Yasuko, Kuwabara, Masachika, Tanaka-Totoribe, Naoko, Kanai, Tasuku, Nakamura, Eisaku, Gamoh, Shuji, Suzuki, Akito, Asada, Yujiro, Hisa, Hiroaki, Yamamoto, Ryuichi
• Format: Article
• Language: English
• Subjects: 5-Hydroxytryptamine (5-HT)-induced vasoconstriction; Aged; Aged, 80 and over; Coronary Artery Bypass; Diabetes mellitus (DM); Diabetes Mellitus - enzymology; Diabetes Mellitus - physiopathology; Endothelium, Vascular - drug effects; Endothelium, Vascular - enzymology; Endothelium, Vascular - physiopathology; Humans; Middle Aged; Myosin light chain phosphatase (MLCP); Myosin-Light-Chain Phosphatase - analysis; Myosin-Light-Chain Phosphatase - metabolism; Receptor, Serotonin, 5-HT1B - analysis; Receptor, Serotonin, 5-HT1B - metabolism; Receptor, Serotonin, 5-HT2A - analysis; Receptor, Serotonin, 5-HT2A - metabolism; rho-Associated Kinases - analysis; rho-Associated Kinases - metabolism; rhoA GTP-Binding Protein - analysis; rhoA GTP-Binding Protein - metabolism; Saphenous Vein - drug effects; Saphenous Vein - enzymology; Saphenous Vein - physiopathology; Serotonin - pharmacology; Tissue and Organ Harvesting; Vasoconstriction
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.07.097

► Effect of DM on vascular reactivity of human saphenous vein was examined. ► The vasoconstrictions to 5-HT were significantly enhanced in the DM. ► The protein level of MLCP was significantly diminished in the DM. ► The ratio of phosphorylated-MLCP to total MLCP was significantly higher in the DM. ► The defective protein level of MLCP is involved in hyperreactivity in the DM. We examined the contractile reactivity to 5-hydroxytryptamine (5-HT) in isolated human saphenous vein (SV), as a vascular conduit in coronary artery bypass grafting (CABG), harvested from patients with diabetes mellitus (DM) and non-DM (NDM). Vascular rings of endothelium-denuded SV were used for functional and biochemical experiments. The vasoconstrictions caused by 5-HT were significantly greater (hyperreactivity) in the DM group than in the NDM group. RhoA/ROCK pathway is activated by various G-protein-coupled receptor agonists and consequently induces phosphorylation of myosin phosphatase target subunit 1 (MYPT1), a subunit of myosin light chain phosphatase (MLCP), which inhibits MLCP activity. In the resting state of the vessels, total tissue protein levels of 5-HT2A receptor, 5-HT1B receptor, RhoA, ROCK1, and ROCK2 did not differ between NDM and DM groups. However, the total protein level of MYPT1 was significantly lower in the DM group than in the NDM group. Furthermore, the ratio of P(Thr696)-MYPT1 to total MYPT1 was significantly higher in the DM group than in the NDM group. These results suggest that the hyperreactivity to 5-HT in the SV smooth muscle of patients with DM is due to not only enhanced phosphorylation of MLCP but also defective protein level of MLCP. Thus, we reveal for the first time that the defective protein level of MLCP in the DM group can partially explain the poor patency of SV graft harvested from patients with DM.