EAS 2012 MILAN
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Professor Majesky and
Professor Landmesser
will take part in the
EAS 2012 Plenary Session
26 May, 2012, 08:30-10:30
CELLULAR AND HUMORAL FACTORS IN THE ARTERIAL WALL DETERMINE THE COURSE OF ATHEROGENESIS AND VASCULAR FUNCTION
Chaired by
Professor Alain Tedgui, France and
Professor Lale Tokgozoglu, Turkey

Focus on... EAS 2012

As we count down to this year's Congress, each week we highlight speakers who will participate in EAS 2012.
This week the speakers in the spotlight are:

Professor Mark Majesky

BUILDING A VESSEL WALL: FROM DEVELOPMENTAL BIOLOGY TO PHYSIOLOGICAL AND PATHOLOGICAL REMODELING IN ADULT LIFE

Mark Majesky is an internationally recognized expert in the field of stem cell biology. He is currently Professor of Pediatrics at the University of Washington, Associate Director of the Center for Tissue and Cell Sciences, and Director of the Myocardial Regeneration Initiative at Seattle Children's Research Institute.

Dr. Majesky’s research is centred on understanding basic mechanisms of formation and repair of blood vessels. A key focus concerns the development and fate of vascular stem/progenitor cells that reside in the adventitial layer of the artery wall.

Coronary progenitors found in the pro-epicardium are the forerunners for the endothelium, smooth muscle and adventitial cells of the coronary vasculature. Defining the mechanisms involved in the differentiation of the embryonic vasculature may provide insights into the formation, regression, remodelling and repair of blood vessels in later life.

Emerging evidence suggests that the adventitia provides a niche-like signalling environment for progenitor stem cells in the artery wall with the capacity to respond to arterial injury. Studies have shown that progenitor cells can be mobilized to differentiate to mural-like cells in vitro, and may promote angiogenesis in vivo. The adventitia is also involved in immune surveillance, inflammation and via the vasa vasorum, acts as a gateway for migration of macrophages and leukocytes into the intima. These findings suggest a potential role for the adventitia in coronary artery repair, remodelling and disease.

Understanding the role of the adventitia may have important application in stem and progenitor cell-based therapies, as well as in the management of congenital heart defects and other cardiac abnormalities.

Key references

Majesky MW, Dong XR, Hoglund V, Mahoney WM Jr, Daum G. The adventitia: a dynamic interface containing resident progenitor cells. Arterioscler Thromb Vasc Biol 2011;31:1530-9.

Majesky MW, Dong XR, Regan JN, Hoglund VJ. Vascular smooth muscle progenitor cells: building and repairing blood vessels. Circ Res 2011;108:365-77.

Hoglund VJ, Majesky MW. Patterning the artery wall by lateral induction of notch signaling. Circulation 2012;125:212-5.

Professor Ulf Landmesser

ENDOTHELIAL FUNCTION AND DYSFUNCTION: THE KEYS TO CORONARY AND PERIPHERAL CIRCULATION

Ulf Landmesser is Professor of Cardiology, Head, Acute and Invasive Cardiology and Head of Cardiovascular Research at the Department of Cardiology of the University Hospital Zurich.

A key focus of his research is progenitor cell-mediated repair capacity in cardiovascular disease.
Prof Landmesser is Deputy Editor, European Heart Journal, and a member of the ESC Congress Program Committee (2010-2012), the Science and Guidelines committee, EACPR and the Nucleus Exercise, Basic and Translational Science, EACPR.

Endothelial dysfunction underlies the development and progression of atherosclerosis and its clinical complications. In particular reduced endothelial availability of nitric oxide (NO), in part due to increased vascular oxidant stress, promotes a pro-inflammatory and prothrombotic phenotype of the endothelium. Clinical studies have shown close association between the degree of endothelial dysfunction and risk of future cardiovascular events. The development of novel methods for evaluating endothelial function offers the possibility for detecting endothelial dysfunction before overt coronary and peripheral vascular disease.

Cardiovascular risk factors reduce the number and impair the function of circulating endothelial progenitor cells, thereby impairing their repair capacity. Understanding these mechanisms may offer a potential therapeutic strategy in ischaemic heart disease. Approaches have been aimed at maintaining stem cell niche function and targeting mobilization/recruitment of specific stem/progenitor cell populations to preserve vascular and cardiac function. Although small studies suggest that cell-based therapy may improve cardiac function on top of standard therapy, there remain limitations and uncertainties.

Ultimately such approaches, combining emerging tools such as cell priming, bionanotechnology and tissue engineering, may offer the opportunity for a combined biological approach to ischaemic tissue repair.

Key references

Landmesser U, Hornig B, Drexler H. Endothelial function: a critical determinant in atherosclerosis ? Circulation 2004; 109(Suppl 1): II27-II33

Lekakis J, Abraham P, Balbarini A, Blann A, Boulanger CM, Cockcroft J, Cosentino F, Deanfield J, Gallino A, Ikonomidis I, Kremastinos D, Landmesser U, Protogerou A, Stefanadis C, Tousoulis D, Vassalli G, Vink H, Werner N, Wilkinson I, Vlachopoulos C. Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur J Cardiovasc Prev Rehabil 2011;18:775-89.

Besler C, Heinrich K, Rohrer L, Doerries C, Riwanto M, Shih DM, Chroni A, Yonekawa K, Stein S, Schaefer N, Mueller M, Akhmedov A, Daniil G, Manes C, Templin C, Wyss C, Maier W, Tanner FC, Matter CM, Corti R, Furlong C, Lusis AJ, von Eckardstein A, Fogelman AM, Lüscher TF, Landmesser U. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest 2011;121:2693-708.

Tongers J, Losordo DW, Landmesser U. Stem and progenitor cell-based therapy in ischaemic heart disease: promise, uncertainties, and challenges. Eur Heart J 2011;32:1197-206.