title: 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).
abstract: 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-HT(2A) receptor, 5-HT(1B) 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(Thr(696))-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.
authors.affiliation: First Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Masachika
authors.initials: M
authors.lastname: Kuwabara
authors.forename: Naoko
authors.initials: N
authors.lastname: Tanaka-Totoribe
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kanai
authors.forename: Eisaku
authors.initials: E
authors.lastname: Nakamura
authors.forename: Shuji
authors.initials: S
authors.lastname: Gamoh
authors.forename: Akito
authors.initials: A
authors.lastname: Suzuki
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Asada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hisa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Yamamoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001026:Coronary Artery Bypass; D003920:Diabetes Mellitus / Q000201:enzymology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D006801:Humans; D008875:Middle Aged; D043263:Myosin-Light-Chain Phosphatase / Q000032:analysis / Q000378:metabolism*; D044302:Receptor, Serotonin, 5-HT1B / Q000032:analysis / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000032:analysis / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D012701:Serotonin / Q000494:pharmacology; D020858:Tissue and Organ Harvesting; D014661:Vasoconstriction; D054460:rho-Associated Kinases / Q000032:analysis / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000032:analysis / Q000378:metabolism
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human; D020742:rhoA GTP-Binding Protein