The EAS is delighted to announce that the recipient of the Society’s prestigious Anitschkow Prize 2013 is Professor Peter Libby, Mallinckrodt Professor of Medicine at Harvard Medical School and Chief of the Cardiovascular Division at Brigham and Women’s Hospital, Boston, Massachusetts.
About the Laureate
Over the past three decades Prof. Libby has made numerous major discoveries that have changed
the way we think about the etiology and potential management of atherosclerotic cardiovascular
disease. Prof. Libby’s seminal experimental and translational observations on the
pathophysiological pathways leading to plaque formation and destabilization have affected our
current knowledge of atherosclerosis with far reaching clinical implications. His work will pave
the way for new strategies designed to prevent the onset and progression of atherosclerosis in
those who do not yet have manifest cardiovascular disease.
Prof. Libby has been a role model, gifted teacher and mentor for a generation of emerging
clinical and basic cardiovascular researchers who have been inspired by his ability to translate
basic research into clinical setting. This has greatly magnified his contribution to the
understanding of atherosclerosis.
- Prof. Libby discovered that vascular wall cells can produce as well as respond to pro inflammatory cytokines. This discovery suggested autocrine and paracrine cytokine inflammatory signalling in arterial disease, and laid the groundwork for a new field in atherosclerosis research for laboratories worldwide. Prof. Libby recently postulated a critical role for CD40 signalling in atherosclerosis and first established the key role of this cytokine signalling pathway in atherogenesis in genetically altered mice.
- Prof. Libby originated the concept that the dynamic metabolism of arterial collagen regulated by inflammatory signals governed the susceptibility of atherosclerotic plaques to disruption and thrombosis. He discovered the inhibition by Th1 cytokines of collagen production by human smooth muscle cells and the overexpression of interstitial collagenases (MMPs 1, 8, 13) in human atheromata. He showed that inhibition of these enzymes can strengthen atheroma by increasing collagen content. He also showed that lipid-lowering can exert anti-inflammatory actions and ameliorate properties of plaques linked to thrombotic complications. This sustained series of discoveries furnished the foundation for current thinking about the molecular basis of the acute coronary syndromes, and the mechanism of benefit of therapies that reduce risk of myocardial infarction and stroke.
- In 1989 Prof. Libby proposed a model for the immunopathogenesis of transplantation arteriopathy. His later experiments in genetically-altered mice proved his original postulates of an alloimmune response to donor vascular cells with a central role of signaling due to interferon-gamma. This model has gained wide acceptance, provided the foundation for much subsequent research and clinical progress in this field.
- In 1993 Prof. Libby showed sustained inflammatory activation of vascular cells following arterial injury. At that time hypotheses of the pathogenesis of restenosis after arterial intervention highlighted thrombosis and arterial smooth muscle cells proliferation. Prof. Libby’s pioneering discovery of the operation of inflammation pathways after arterial injury laid the scientific foundation for the clinical success of the immunosuppressive agents in drug-eluting stents.
- Prof. Libby has recently elucidated a mechanism that explains the dimorphic expression of atherosclerosis, which is sometimes stenotic, sometimes aneurysmal. In a landmark publication Prof. Libby showed a Th1-skewed response in typical 2 atherosclerosis but a predominant Th2 response in human aortic aneurysmal disease. Subsequent work in genetically altered mice has substantiated the concept that Th1/Th2 balance plays a key role in the pathogenesis of arterial aneurysms.
- Prof. Libby has recently developed methods for the molecular imaging of vascular inflammation. In particular, his laboratory has established and validated techniques that visualize the activity of the matrix metalloproteinase he previously showed were produced by inflammatory cells in atherosclerotic plaques. These proteinases degrade arterial collagen, weakening the plaques fibrous, and thus heightening the risk of the thrombotic complications of atherosclerosis.
- Finally, Prof. Libby has fostered the rapid translation to the clinic of the concepts of inflammation in arterial pathophysiology that emerged from his own laboratory work over the last twenty years. He has inspired, enabled, and participated in a number of the clinical studies that have placed inflammation at the forefront of current thinking about the diagnosis, risk stratification, and therapeutic approaches to atherosclerotic cardiovascular disease.
REFERENCES
- Libby P, Ordovàs JM, Auger KR, Robbins H, Birinyi LK, Dinarello CA. Endotoxin and tumor
necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells.
Am. J. Path. 1986;124:179 – 186. - Salomon RN, Hughes CCW, Schoen FJ, Payne DD, Pober JS, Libby P. Human coronary
transplantation-associated arteriosclerosis: Evidence for a chronic immune reaction to activated
graft endothelial cells. Am J Pathol. 1991;138(4):791-798. - Tanaka H, Sukhova G, Swanson S, Clinton S, Ganz P, Cybulsky M, Libby P. Sustained
activation of vascular cells and leukocytes in the rabbit aorta after balloon injury. Circulation.
1993;88(4):1788-1803. - Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P. Reduction of atherosclerosis in
mice by inhibition of CD40 signalling. Nature. 1998;394(6689):200-203. - Aikawa M, Rabkin E, Okada Y, Voglic SJ, Clinton SK, Brinckerhoff CE, Sukhova GK, Libby
P. Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen
content of rabbit atheroma: a potential mechanism of lesion stabilization. Circulation.
1998;97:2433-2444. - Nagano H, Mitchell RN, Taylor MK, Hasegawa S, Tilney NL, Libby P. Interferon-gamma
deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse
hearts. Journal of Clinical Investigation. 1997;100(3):550-557. - Sukhova GK, Schonbeck U, Rabkin E, Schoen FJ, Poole AR, Billinghurst RC, Libby P.
Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human
atheromatous plaques. Circulation. 1999;99(19):2503- 2509. - Deguchi J-O, Aikawa M, Tung C-H. Aikawa E, Kim D-O, Ntziachristos V, Weissleder R,
Libby P. Inflammation in atherosclerosis: visualizing matrix metalloproteinase action in
macrophages in vivo. Circulation 2006;114:55-62. - Christen T, Nahrendorf M, Wildgruber M, Swirski FK, Aikawa E, Waterman P, Shimizu K,
Weissleder R, Libby P. Molecular imaging of innate immune cell function in transplant
rejection. Circulation 2009;119:1925-1932. - Quillard T, Tesmenitsky Y, Croce K, Travers R, Shvartz E, Koskinas KC, Sukhova G,
Aikawa E, Aikawa M, Libby P. Selective inhibition of matrix metalloproteinase 13 (MMP-13)
increases collagen content of established mouse atheromata. Arterioscler Thromb Vasc Biol
2011;31(11):2464-2472.