Inflamación en ateroesclerosis

Journal of the American College of Cardiology © 2009 by the American College of Cardiology Foundation Published by Elsevier Inc.

Vol. 54, No. 23, 2009 ISSN 0735-1097/09/$36.00 doi:10.1016/j.jacc.2009.09.009

STATE-OF-THE-ART PAPER

Inflammation in Atherosclerosis
From Pathophysiology to Practice
Peter Libby, MD,* Paul M Ridker, MD, MPH,*† Göran K. Hansson, MD, PHD,‡ for the LeducqTransatlantic Network on Atherothrombosis Boston, Massachusetts; and Stockholm, Sweden
Until recently, most envisaged atherosclerosis as a bland arterial collection of cholesterol, complicated by smooth muscle cell accumulation. According to that concept, endothelial denuding injury led to platelet aggregation and release of platelet factors which would trigger the proliferation of smooth muscle cellsin the arterial intima. These cells would then elaborate an extracellular matrix that would entrap lipoproteins, forming the nidus of the atherosclerotic plaque. Beyond the vascular smooth muscle cells long recognized in atherosclerotic lesions, subsequent investigations identified immune cells and mediators at work in atheromata, implicating inflammation in this disease. Multiple independentpathways of evidence now pinpoint inflammation as a key regulatory process that links multiple risk factors for atherosclerosis and its complications with altered arterial biology. Knowledge has burgeoned regarding the operation of both innate and adaptive arms of immunity in atherogenesis, their interplay, and the balance of stimulatory and inhibitory pathways that regulate their participation inatheroma formation and complication. This revolution in our thinking about the pathophysiology of atherosclerosis has now begun to provide clinical insight and practical tools that may aid patient management. This review provides an update of the role of inflammation in atherogenesis and highlights how translation of these advances in basic science promises to change clinical practice. (J Am Coll Cardiol2009;54:2129–38) © 2009 by the American College of Cardiology Foundation

Just 3 decades ago the prevailing viewpoint envisaged atherosclerosis as a bland proliferative process (1). According to that concept, endothelial denuding injury led to platelet aggregation and release of platelet-derived growth factor that would trigger the proliferation of smooth muscle cells in the arterial intima, andform the nidus of the atherosclerotic plaque. This cellular model of atherosclerosis updated Virchow’s concepts of atherosclerosis as a response to injury formulated in the mid-19th

From the *Division of Cardiovascular Medicine, Department of Medicine, and the †Division of Cardiovascular Medicine, Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, HarvardMedical School, Boston, Massachusetts; and the ‡Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. This work was supported by grants from the Fondation Leducq (to Drs. Libby, Ridker, and Hansson), the Swedish Research Council (to Dr. Hansson), the Swedish Heart-Lung Foundation (to Dr. Hansson), and the Donald W. ReynoldsFoundation (to Drs. Libby and Ridker). Dr. Libby is an unpaid consultant to AstraZeneca. Dr. Ridker has received research funding support from multiple not-for-profit entities including the National Heart, Lung, and Blood Institute, the National Cancer Institute, the American Heart Association, the Doris Duke Charitable Foundation, the Leducq Foundation, the Donald W. Reynolds Foundation, and theJames and Polly Annenberg La Vea Charitable Trusts; he has also received investigator-initiated research support from multiple for-profit entities including AstraZeneca, Novartis, Pharmacia, Roche, Sanofi-Aventis, and Abbott, as well as nonfinancial research support from Amgen. In addition, he is listed as a coinventor on patents held by the Brigham and Women’s Hospital that relate to the use of...