Author + information
- Received January 9, 2019
- Revision received June 12, 2019
- Accepted July 7, 2019
- Published online September 16, 2019.
- aDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- bDepartment of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
- ↵∗Address for 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.
• Concepts of the pathophysiology of atherosclerosis have changed considerably over the years.
• Many traditionally regarded atherosclerosis as mere lipid buildup on the arterial wall.
• Advances in vascular biology permitted experimental study of endothelial and smooth muscle cells.
• The concept then prevailed that atheroma arise from bland excessive proliferation of smooth muscle cells.
• Dysfunction of an intact endothelium replaced denuding injury as key in atherogenesis.
• Recent concepts invoke inflammation as a key mediator between risk factors and artery wall cells.
• Advances in understanding inflammation in atherosclerosis has led us to novel therapeutic strategies.
Concepts of atherogenesis have evolved considerably with time. Early animal experiments showed that a cholesterol-rich diet could induce fatty lesion formation in arteries. The elucidation of lipoprotein metabolism ultimately led to demonstrating the clinical benefits of lipid lowering. The view of atheromata as bland accumulations of smooth muscle cells that elaborated an extracellular matrix that could entrap lipids then expanded to embrace inflammation as providing pathways that could link risk factors to atherogenesis. The characterization of leukocyte adhesion molecules and their control by proinflammatory cytokines, the ability of chemokines to recruit leukocytes, and the identification of inflammatory cell subtypes in lesions spurred the unraveling of innate and adaptive immune pathways that contribute to atherosclerosis and its thrombotic complications. Such pathophysiologic insights have led to the identification of biomarkers that can define categories of risk and direct therapies and to the development of new treatments.
Dr. Libby has received funding from the National Heart, Lung, and Blood Institute (R01HL080472 and R01HL134892), the American Heart Association (18CSA34080399), and the RRM Charitable Fund; has served as an unpaid consultant or has been involved in clinical trials for Amgen, AstraZeneca, Esperion Therapeutics, Ionis Pharmaceuticals, Kowa Pharmaceuticals, Novartis, Pfizer, Sanofi-Regeneron, and XBiotech, Inc.; has served on the Scientific Advisory Board for Amgen, Athera Biotechnologies, Corvidia Therapeutics, DalCor Pharmaceuticals, IFM Therapeutics, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, and Novartis; and has received laboratory funding in the last 2 years from Novartis. Dr. Hansson is funded by the Swedish Research Council (grant 2016-02738), the Swedish Heart-Lung Foundation, and Research funds of the Stockholm County Council; and has been listed as co-inventor on patents relating to cardiovascular therapy.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received January 9, 2019.
- Revision received June 12, 2019.
- Accepted July 7, 2019.
- 2019 American College of Cardiology Foundation
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