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: Yasuko Matsuo, Masachika Kuwabara, Naoko Tanaka-Totoribe, Tasuku Kanai, Eisaku Nakamura, Shuji Gamoh, Akito Suzuki, Yujiro Asada, Hiroaki Hisa, Ryuichi Yamamoto
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 412 Issue 2 Pg. 323-7 (Aug 26 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 21821002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Receptor, Serotonin, 5-HT1B
• Receptor, Serotonin, 5-HT2A
• Serotonin
• ROCK1 protein, human
• ROCK2 protein, human
• rho-Associated Kinases
• Myosin-Light-Chain Phosphatase
• PPP1R12A protein, human
• rhoA GTP-Binding Protein

Topics

• Aged
• Aged, 80 and over
• Coronary Artery Bypass
• Diabetes Mellitus (enzymology, physiopathology)
• Endothelium, Vascular (drug effects, enzymology, physiopathology)
• Humans
• Middle Aged
• Myosin-Light-Chain Phosphatase (analysis, metabolism)
• Receptor, Serotonin, 5-HT1B (analysis, metabolism)
• Receptor, Serotonin, 5-HT2A (analysis, metabolism)
• Saphenous Vein (drug effects, enzymology, physiopathology)
• Serotonin (pharmacology)
• Tissue and Organ Harvesting
• Vasoconstriction
• rho-Associated Kinases (analysis, metabolism)
• rhoA GTP-Binding Protein (analysis, metabolism)