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(Circulation. 2006;114:1811-1820.)
© 2006 American Heart Association, Inc.

Genetics

Transcriptional Profiling in Coronary Artery Disease

Indications for Novel Markers of Coronary Collateralization

Thomas W. Chittenden, PhD; Jonathan A. Sherman, MD; Fei Xiong, MEng; Amy E. Hall, BS; Anthony A. Lanahan, PhD; Jennifer M. Taylor, PhD; Hangjun Duan, PhD; Justin D. Pearlman, MD, PhD; Jason H. Moore, PhD; Stephen M. Schwartz, MD, PhD; Michael Simons, MD

From the Angiogenesis Research Center (T.W.C., J.A.S., A.E.H., A.L., J.P., M.S.), Section of Cardiology, Departments of Medicine (T.W.C., J.A.S., A.E.H., A.A.L., J.D.P., M.S.), Pharmacology and Toxicology (M.S.), and Radiology (J.D.P.), and Norris Cotton Cancer Center, Department of Genetics (J.H.M.), Dartmouth Medical School, Hanover, NH; Bioinformatics Programme, Department of Statistics (T.W.C., J.A.S.), and Wellcome Trust Centre for Human Genetics (J.M.T.), University of Oxford, Oxford, UK; Department of Computer Science (F.X., J.D.P.), Dartmouth College, Hanover, NH; and Department of Pathology (H.D., S.M.S.), University of Washington, Seattle.

Correspondence to Michael Simons, MD, Section of Cardiology, Dartmouth Hitchcock Medical Center, 1 Medical Center Dr, Lebanon, NH 03755. E-mail michael.simons{at}dartmouth.edu

Received March 20, 2006; revision received August 1, 2006; accepted August 11, 2006.

Background— The development of collateral circulation plays an important role in protecting tissues from ischemic damage, and its stimulation has emerged as one of principal approaches to therapeutic angiogenesis. Clinical observations have documented substantial differences in the extent of collateralization among patients with coronary artery disease (CAD), with some individuals demonstrating marked abundance and others showing nearly complete absence of these vessels. Recent studies have suggested that circulating monocytes play a major role in collateral growth. The present study was undertaken to determine transcriptional profiles of circulating monocytes in CAD patients with different extents of collateral growth.

Methods and Results— Monocyte transcriptomes from CAD patients with and without collateral vessels were obtained by use of high-throughput expression profiling. Using a newly developed redundancy-based data mining method, we have identified a set of molecular markers characteristic of a "noncollateralgenic" phenotype. Moreover, we show that these transcriptional abnormalities are independent of the severity of CAD or any other known clinical parameter thought to affect collateral development and correlated with protein expression levels in monocytes and plasma.

Conclusions— Monocyte transcription profiling identifies sets of patients with extensive versus poorly developed collateral circulation. Thus, genetic factors may heavily influence coronary collateral vessel growth in CAD and affect prognosis and response to therapeutic interventions.

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