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Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin

^* Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga, Japan

Manuscript received June 13, 2003; revised manuscript received March 25, 2004, accepted March 30, 2004.

^* Reprint requests and correspondence: Dr. Tetsuya Matsumoto, Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga 520-2192, Japan.
tetsuyam{at}belle.shiga-med.ac.jp

OBJECTIVES: We examined the relationship between coronary endothelium-dependent vasodilation in response to bradykinin (BK) and plasma levels of oxidized low-density lipoprotein (oxLDL) in subjects with normal coronary arteries.

BACKGROUND: It is unclear whether the plasma oxLDL level is a determinant of coronary endothelial function. Bradykinin plays an important role in regulating resting coronary tone and flow-mediated coronary vasomotion.

METHODS: Coronary blood flow (CBF) in the left anterior descending (LAD) coronary artery was assessed by quantitative angiography and a Doppler flow wire in 94 consecutive subjects with normal coronary arteries. The plasma oxLDL level was measured by enzyme-linked immunosorbent assay using DLH3R, a specific antibody against oxLDL.

RESULTS: Plasma levels of oxLDL in diabetic subjects (n = 13) were higher than those in non-diabetic subjects (n = 81). Plasma levels of oxLDL correlated with body mass index (BMI). Bradykinin at doses of 0.2, 0.6, and 2.0 µg/min caused dose-dependent increases in diameter and CBF in the LAD coronary artery. By a univariate analysis, oxLDL levels significantly correlated with epicardial (r = –0.30, p < 0.0001) and resistant (r = –0.36, p = 0.003) coronary vasodilator responses to BK at 2.0 µg/min, whereas total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were not associated with these coronary responses. In a stepwise multivariate analysis, oxLDL levels were significantly correlated with epicardial and resistant coronary vasomotor responses to BK, independent of age, gender, smoking status, other lipid levels, BMI, hypertension, and diabetes.

CONCLUSIONS: The plasma level of oxLDL is an appropriate surrogate for assessing coronary endothelial-dependent vasomotor function as estimated by responses to BK compared with conventional risk factors for atherosclerosis.

Abbreviations and Acronyms   BK = bradykinin   BMI = body mass index   CAD = coronary artery disease   CBF = coronary blood flow   HDL = high-density lipoprotein   LAD = left anterior descending   LDL = low-density lipoprotein   NO = nitric oxide   oxLDL = oxidized low-density lipoprotein

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