Increased RhoA/ROK mRNA expression and function in diabetic vein grafts compared with nondiabetic vein grafts and diabetic arterial grafts

Thorac Cardiovasc Surg. 2010 Apr;58(3):148-53. doi: 10.1055/s-0029-1186267. Epub 2010 Apr 7.

Abstract

Objective: Aim of the study was to discuss a new mechanism underlying the poor graft patency of GSV from diabetic patients and provide a rationale for selecting suitable grafts in diabetic patients.

Materials and methods: The discarded matched RA, IMA, and GSV from 7 diabetics and 7 nondiabetic patients undergoing CABG were collected and tested for their contractile response to phenylephrine (PE) and their relaxation response to fasudil (a inhibitor of Rho-kinase) and used for immunohistochemical and mRNA detection of RhoA/ROK.

Results: The relaxation response to fasudil of GSV taken from diabetic patients was markedly increased but the relaxation response to fasudil of IMA and RA from diabetic patients was not. Immunohistochemistry and mRNA expression of RhoA/ROK was significantly increased in GSV from diabetic patients compared to that of IMA and RA from diabetic patients. RhoA/ROK immunohistochemistry and mRNA expression were significantly increased in GSV from diabetic patients compared with GSV from nondiabetic controls.

Conclusions: RhoA/ROK expression and function in GSV from diabetic patients is significantly increased compared with IMA and RA from diabetic patients and GSV from nondiabetic patients. This contributes to a higher incidence of atherosclerosis and a lower long-term patency of GSV from diabetic patients.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Adult
  • Aged
  • Case-Control Studies
  • Coronary Artery Bypass* / adverse effects
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / enzymology
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / surgery*
  • Diabetes Mellitus / enzymology*
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / physiopathology
  • Female
  • Gene Expression Regulation, Enzymologic
  • Graft Occlusion, Vascular / enzymology
  • Graft Occlusion, Vascular / etiology
  • Humans
  • Immunohistochemistry
  • Male
  • Mammary Arteries / enzymology
  • Middle Aged
  • Phenylephrine / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Messenger / analysis*
  • Radial Artery / enzymology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Saphenous Vein / drug effects
  • Saphenous Vein / enzymology*
  • Saphenous Vein / physiopathology
  • Saphenous Vein / transplantation*
  • Vascular Patency
  • Vasoconstriction
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / genetics*
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / genetics*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Vasoconstrictor Agents
  • RHOA protein, human
  • Phenylephrine
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein
  • fasudil