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Presence of asymmetric dimethylarginine gradients across high-grade lesions in patients with coronary artery disease

Joyal, Dominiquea; Leya, Ferdinanda; Obada Al-Chekakie, M.a; Arab, Dinesha; Dieter, Robert S.a; Morshedi-Meibodi, Alia; Lewis, Brucea; Steen, Lowella; Fareed, Jawedb; Hoppenstead, Debrab; Akar, Joseph G.a

doi: 10.1097/MCA.0b013e32818be79c
Diagnostic Methods
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Background Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is a systemic marker of endothelial dysfunction. Although experimental evidence indicates that asymmetric dimethylarginine may play an important role in atherogenesis, local asymmetric dimethylarginine levels have not been measured in vivo.

Objectives We sought to determine whether: (i) asymmetric dimethylarginine is elevated locally at sites of coronary lesions, (ii) systemic asymmetric dimethylarginine concentrations correlate with local levels, and (iii) percutaneous coronary intervention produces immediate local asymmetric dimethylarginine elevation.

Methods In patients undergoing percutaneous coronary intervention (n=15), blood samples were obtained from a peripheral venous site, the coronary ostium proximal to the lesion and the coronary vessel distal to the lesion, before percutaneous coronary intervention. Samples were also obtained distal to the coronary lesion immediately after percutaneous coronary intervention and from the peripheral venous line 24 h after percutaneous coronary intervention.

Results Asymmetric dimethylarginine gradients were present across the coronary bed: local asymmetric dimethylarginine (μmol/l) was significantly higher distal to coronary lesions compared with proximally (2.39±1.27 vs. 1.52±0.68, P=0.005), and to systemic venous levels (2.39±1.27 vs. 1.17±0.72, P=0.001). Local asymmetric dimethylarginine did not increase immediately after percutaneous coronary intervention (1.88±0.89 vs. 2.39±1.27, P=0.11). Peripheral venous percutaneous coronary intervention levels 24 h after percutaneous coronary intervention were similar to baseline values (1.17±1.2 vs. 1.17±0.72, P=0.98).

Conclusion Asymmetric dimethylarginine gradients exist across coronary lesions, suggesting asymmetric dimethylarginine release at the plaque site. Local asymmetric dimethylarginine accumulation may contribute to the endothelial dysfunction associated with high-grade coronary lesions. Peripheral asymmetric dimethylarginine is a marker of generalized endothelial dysfunction, but our findings highlight its limitation in detecting focal injury.

aDepartment of Medicine, Division of Cardiology

bDepartment of Pathology, Loyola University Medical Center, Maywood, Illinois, USA

Correspondence to Dr Joseph Akar, MD, PhD, Loyola University Medical Center, Division of Cardiology, 2160 S First Avenue, Bldg 110/6222, Maywood, IL, 60153, USA

Tel: +708 216 8481; fax: +708 216 6829; e-mail: jakar@lumc.edu

Received 19 January 2007 Accepted 19 March 2007

© 2007 Lippincott Williams & Wilkins, Inc.