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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 Leducq Transatlantic Network on Atherothrombosis

^_* Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
Division of Cardiovascular Medicine, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

Manuscript received February 27, 2009; revised manuscript received September 4, 2009, accepted September 6, 2009.

^_* Reprint requests and correspondence: Dr. Peter Libby, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115 (Email: plibby{at}rics.bwh.harvard.edu).

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 cells in 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 independent pathways 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 in atheroma 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.

Key Words: atherosclerosis • inflammation • heart disease

Abbreviations and Acronyms   CRP = C-reactive protein   GWAS = genome-wide association screen   hsCRP = high-sensitivity C-reactive protein   LDL = low-density lipoprotein   LDL-C = low-density lipoprotein cholesterol   NNT = number needed to treat   TLR = Toll-like receptor   Treg = regulatory T cell

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