Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin.
OBJECTIVE
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 microg/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 microg/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.
Matsumoto
Tetsuya
T
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga, Japan. tetsuyam@belle.shiga-med.ac.jp
Takashima
Hiroyuki
H
Ohira
Naoto
N
Tarutani
Yasuhiro
Y
Yasuda
Yo
Y
Yamane
Tetsunobu
T
Matsuo
Shinro
S
Horie
Minoru
M
D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity; D015992:Body Mass Index; D001920:Bradykinin / Q000494:pharmacology*; D017023:Coronary Angiography; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000502:physiology* / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D014664:Vasodilation / Q000187:drug effects*
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D001920:Bradykinin