Increased leukocyte Rho-associated coiled-coil containing protein kinase activity predicts the presence and severity of coronary vasospastic angina

Hung, Ming-Jui; Cherng, Wen-Jin; Hung, Ming-Yow; Kuo, Li-Tang; Cheng, Chi-Wen; Wang, Chao-Hung; Yang, Ning-I; Liao, James K.

doi:10.1016/j.atherosclerosis.2012.01.001

« Previous Next »Atherosclerosis
Volume 221, Issue 2 , Pages 521-526, April 2012

Increased leukocyte Rho-associated coiled-coil containing protein kinase activity predicts the presence and severity of coronary vasospastic angina

Ming-Jui Hung
- Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan
Wen-Jin Cherng
- Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan
Ming-Yow Hung
- Department of Cardiology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
Li-Tang Kuo
- Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan
Chi-Wen Cheng
- Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan
Chao-Hung Wang
- Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan
Ning-I Yang
- Department of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan
James K. Liao
- Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
- Corresponding author at: Brigham and Women's Hospital, 65 Landsdowne Street, Room 275, Cambridge, Massachusetts 02139, United States. Tel.: +1 617 768 8424; fax: +1 617 768 8425.

Received 8 August 2011; received in revised form 7 December 2011; accepted 3 January 2012. published online 31 January 2012.

Highlights

► ROCK activity increased with the severity of CVA. ► Increased ROCK activity predicted the presence of CVA. ► Treatment with antispastic agents reduced the level of ROCK activity.

Abstract

Objective

Although inhibition of Rho-associated coiled-coil containing protein kinase (ROCK) has been shown to prevent coronary vasospastic angina (CVA), direct evidence linking ROCK activity and CVA is lacking. Accordingly, we investigated whether ROCK activity is an independent marker for CVA and is altered after treatment with antispastic medications.

Methods and results

We prospectively studied 31 Taiwanese patients who were diagnosed with CVA and 33 control subjects. Subject demographics were recorded, and blood samples were obtained at baseline in all participants and in CVA patients after 3 months of antispastic treatment. Compared with control subjects, leukocyte ROCK activity was greater in CVA patients (136% versus 91%, P<0.001). A cutoff value for leukocyte ROCK activity of 104% predicted the presence of CVA with specificity and sensitivity rates of 88% and 84%, respectively. ROCK activity increased with the severity of CVA (P for trend<0.001). Following 3-month treatment of antispastic agents, leukocyte ROCK activity, high-sensitivity C-reactive protein, and interleukin-6 levels were reduced by 43%, 42% and 27%, respectively (P<0.05 for all).

Conclusions

Increased levels of leukocyte ROCK activity independently predicted the presence of CVA and correlated with CVA severity. Treatment with antispastic agents substantially reduced the level of leukocyte ROCK activity.

Keywords: Angina, Calcium antagonist, Coronary vasospasm, Rho-kinase