RhoA/ROK pathway related to the mechanism of higher susceptibility to spasm in RA than in IMA.
OBJECTIVE
By investigating the expression and function of RhoA/Rho kinase pathway in the radial artery (RA), internal mammary artery (IMA), and great saphenous vein (GSV), this study aimed to elucidate the mechanism for a higher susceptibility of spasm in the RA and provide an effective drug candidate to prevent and treat RA spasm.


METHODS
RA, IMA, and GSV that would otherwise have been discarded were collected from 25 patients who underwent coronary artery bypass grafting. Eleven matched rings of RA, IMA, and GSV were used to evaluate the vasodilatory properties of 10(-7-)10(-4) mol/l of fasudil, a Rho-kinase inhibitor, by using in vitro organ chambers. Another 14 matched RA, IMA, and GSV were used to demonstrate the immunohistochemistry (IHC) of RhoA and mRNA of RhoA and Rho kinase.


RESULTS
The maximal vasodilation of RA to fasudil was significantly greater than IMA. RhoA protein IHC staining was different in IMA, RA, and GSV (RA > GSV >IMA). The expression of RhoA and Rho kinase mRNA in the RA was significantly greater than in the IMA.


CONCLUSIONS
The expression of RhoA/Rho kinase mRNA and protein and function in the RA were significantly stronger than in the IMA, suggesting that RhoA/Rho kinase pathway may be one mechanism by which RA is more susceptible to spasm than IMA. Rho kinase inhibitors can be effective drug candidates to prevent and treat vasospasm.
Kun
Xia
X
Heart Center of Beijing Chaoyang Hospital affiliated with CUMS, Beijing, China.
Lefeng
Wang
W
Rongjing
Ding
D
Xincun
Yang
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000601:surgery; D003329:Coronary Vasospasm / Q000235:genetics / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D017534:Radial Artery / Q000187:drug effects* / Q000378:metabolism*; D012501:Saphenous Vein / Q000187:drug effects* / Q000378:metabolism*; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects / Q000235:genetics*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000235:genetics*
D012333:RNA, Messenger; C066737:RHOA protein, human; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C105243:RHOD protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C049347:fasudil