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CLINICAL RESEARCH: METABOLIC SYNDROME

Increased Rho Kinase Activity in a Taiwanese Population With Metabolic Syndrome

Ping-Yen Liu, MD, PhD^_*,,, Jyh-Hong Chen, MD, PhD, FACC^_*,, Li-Jen Lin, MD^_*, and James K. Liao, MD, FACC^,_*

^_* Division of Cardiology, Internal Medicine
Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan
Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Manuscript received October 23, 2006; revised manuscript received December 4, 2006, accepted December 19, 2006.

^_* Reprint requests and correspondence: Dr. James K. Liao, Brigham and Women's Hospital, 65 Landsdowne Street, Room 275, Cambridge, Massachusetts 02139. (Email: jliao{at}rics.bwh.harvard.edu).

Objectives: We sought to determine whether Rho kinase (ROCK) activity is increased in a Taiwanese population with metabolic syndrome (MetS).

Background: Recent studies suggest that ROCK may be involved in the pathogenesis of MetS, but clinical studies linking ROCK with MetS are lacking.

Methods: We studied 40 Taiwanese subjects (60% men, mean age 55.5 ± 5.6 years) who were diagnosed with MetS with National Cholesterol Educational Program Adult Treatment Panel III criteria and 40 age- and gender-matched control subjects. Subject demographics were recorded, and blood samples were obtained.

Results: Compared with control subjects, ROCK activity, as determined by phosphorylation of myosin binding subunit (MBS) in leukocytes, was greater in MetS subjects (mean phospho-MBS/MBS ratio 0.46 vs. 0.35, p = 0.002). A cutoff value for ROCK activity of 0.39 predicted the presence of MetS with specificity and sensitivity rates of 70%. Plasma high-sensitivity C-reactive protein was greater (5.5 mg/l, 95% confidence interval [CI] 3.1 to 7.2 mg/l vs. 2.8 mg/l, 95% CI 1.1 to 3.9 mg/l, p = 0.01) and adiponectin was lower (4.9 µg/ml, 95% CI 3.2 to 6.1 µg/ml vs. 5.9 µg/ml, 95% CI 4.2 to 7.5 µg/ml, p = 0.01) in MetS subjects compared with control subjects, but plasma levels of interleukin-6 and tumor necrosis factor-alpha were not different (p > 0.05 for both). Body mass index, waist circumference, fasting glucose, high-sensitivity C-reactive protein, and triglyceride levels were associated with increased levels of ROCK activity. The risk of increased ROCK activity increased with the number of MetS components (p for trend <0.001).

Conclusions: Rho kinase activity is increased in Taiwanese subjects with MetS and is associated with each component of MetS and markers of inflammation. These findings suggest that ROCK activity may be a novel serological marker of MetS.

Abbreviations and Acronyms   BMI = body mass index   HBSS = Hanks' balanced salt solution   HDL-C = high-density lipoprotein cholesterol   hs-CRP = high-sensitivity C-reactive protein   IL = interleukin   IRS = insulin receptor substrate   MBS = myosin binding subunit   MetS = metabolic syndrome   ROCK = Rho kinase   TG = triglycerides   TNF = tumor necrosis factor

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