This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: j.jacc.2006.12.045v1 49/15/1589    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Miller, D. T. Articles by Kwiatkowski, D. J. Search for Related Content PubMed Articles by Miller, D. T. Articles by Kwiatkowski, D. J.

CARDIOVASCULAR GENOMIC MEDICINE

Atherosclerosis

The Path From Genomics to Therapeutics

David T. Miller, MD, PhD^_*,,1, Paul M. Ridker, MD, MPH, FACC^,,,2, Peter Libby, MD, FACC^,,_* and David J. Kwiatkowski, MD, PhD^_*,

^_* Division of Hematology, Brigham and Women’s Hospital, Boston, Massachusetts
Division of Preventive Medicine and Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Boston, Massachusetts
Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
Donald W. Reynolds Cardiovascular Clinical Research Center on Atherosclerosis at Brigham and Women’s Hospital and the Harvard Medical School, Boston, Massachusetts.

Manuscript received June 6, 2006; revised manuscript received October 30, 2006, accepted December 4, 2006.

^_* Reprint requests and correspondence: Dr. Peter Libby, Donald W. Reynolds Cardiovascular Clinical Research Center, Cardiovascular Medicine, Brigham and Women’s Hospital, Mallinckrodt Professor of Medicine, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 7, Boston, Massachusetts 02115. (Email: plibby{at}rics.bwh.harvard.edu).

Recent rapid advances in genomic tools and techniques hold great promise for transforming the practice of cardiovascular medicine. Resources including the Human Genome Project and the International HapMap project, major technological advances in high-throughput genotyping and methods of statistical analysis, and methods for high-throughput gene expression and small molecule profiling allow researchers to confront issues that will fundamentally change the practice of cardiovascular medicine during the 21st century. Genomic, proteomic, and metabolomic studies of complex cardiovascular diseases such as atherosclerosis will bridge epidemiology and basic biology, and promise increased understanding of cardiovascular disease processes. Genetic approaches applied to atherosclerosis will continue to identify genes and pathways involved in the predisposition to and pathophysiology of atherosclerosis. Gene expression profiling refines our understanding of the dynamic nature of the atherosclerotic vascular wall and promises discovery and validation of targets for therapeutic intervention. Opportunities to translate genetic, genomic, proteomic, and metabolomic information into cardiovascular clinical practice have never been greater, but their fruition requires validation in large independent cohorts, achieved only through collaborative effort. Their continued success will depend on ongoing cooperation within the cardiovascular research community.

Abbreviations and Acronyms   ALOX5AP = 5-lipoxygenase activating protein gene   CAD = coronary artery disease   CRP = C-reactive protein   FLAP = 5-lipoxygenase activating protein   HMG-CoA = 5-hydroxy-3-methylglutaryl-coenzyme A   HSP27 = heat shock protein-27   LDL = low-density lipoprotein   LTA4H = leukotriene A4 hydrolase gene   LTB4 = leukotriene B4   MI = myocardial infarction   MMP = matrix metalloproteinase   OR = odds ratio   Osm = oncostatin M   Osmr = oncostatin M receptor   PCSK9 = proprotein convertase subtilisin/kexin type 9 serine protease   SNP = single nucleotide polymorphism   TNFSF4 = tumor necrosis factor (ligand) superfamily, member 4

This article has been cited by other articles:

				B. D. Lamon and D. P. Hajjar Inflammation at the Molecular Interface of Atherogenesis: An Anthropological Journey Am. J. Pathol., November 1, 2008; 173(5): 1253 - 1264. [Abstract] [Full Text] [PDF]

				A. V. G. Edwards, M. Y. White, and S. J. Cordwell The Role of Proteomics in Clinical Cardiovascular Biomarker Discovery Mol. Cell. Proteomics, October 1, 2008; 7(10): 1824 - 1837. [Abstract] [Full Text] [PDF]

				S. B. Damani and E. J. Topol Future Use of Genomics in Coronary Artery Disease J. Am. Coll. Cardiol., November 13, 2007; 50(20): 1933 - 1940. [Abstract] [Full Text] [PDF]