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Cardiovascular research
Research Hub: Cardiovascular Research
S. David Gertz, MD, PhD

Diseases of the heart and peripheral blood vessels remain the leading cause of death worldwide with arteriosclerosis being the most common underlying pathogenetic entity.  Over 200 risk factors have been identified for coronary and peripheral artery disease.  Prominent among these are cigarette smoking, hyperlipidemias, hypertension, obesity, diabetes, and stressful and sedentary lifestyles.  Rigorous risk factor modification has improved morbidity, and revascularization of severely stenotic, clinically significant coronary arteries-- including stent implantation and bypass grafts--have provided major contributions to the reduction in the frequency of acute coronary syndromes and death.  However, the catastrophic consequences of arteriosclerotic stenosis, with sudden or gradual arterial occlusion, remain to take a heavy toll on the heart, other organs, and limbs of millions whose treatment was either not sought, delayed, or ineffective.  A full one-third to one-half of all who die as a result of an acute myocardial infarction experience no symptoms prior to the fatal event.    This underscores the great need for additional advances in clinically applicable, mechanism-based prevention of arteriosclerotic plaque formation as well as more effective strategies for regression therapy.   With the advent of multidetector CT and cardiac MRI, considerable progress has been made in the field of non-invasive imaging of coronary artery stenoses.  However, the non-invasive identification of plaque components subtending lesions likely to rupture and cause an acute coronary event will require significant additional improvement to the currently available instrumentation such as use of hybrid constructs, more advanced molecular imaging, and more sophisticated post-acquisitional analysis. 

Although diseases of the coronary arteries (primarily arteriosclerosis) account for the overwhelming majority of circumstances of failure of the heart to function to capacity, proper functioning of the heart is dependent upon maintenance of structural and functional integrity of three additional physiological systems.  These include the heart muscle itself, the valves that ensure that the heart pumps the blood in the proper direction, and the conduction system that is responsible for the physiologically appropriate distribution of electrical activity for heart muscle contraction.   Examples of disorders involving these systems include hypertrophic cardiomyopathy (cardiac muscle) that is the most common cause of sudden death in young athletes, rheumatic heart disease (valves) that can markedly disrupt the flow of blood through the heart, and a variety of disorders of cardiac rhythm which may be atrial or ventricular in origin, and that may or may not be associated with coronary artery stenosis or occlusion.  Added to these scenarios are the numerous congenital heart defects that are found to range between 0.4% to as many as 7.5% of individuals depending on type and classification.  
Collectively, cardiovascular diseases and their consequences constitute a larger burden on health care delivery systems than any other disease group.  Nonetheless, in Israel and worldwide, the level of support for efforts to develop new therapies for these devastating conditions has been far below their relative impact on life expectancy and quality.  The Cardiovascular Research Hub of the Faculty of Medicine and IMRIC has been established to provide a centralized mechanism for scientific collaboration to address the major problems in cardiovascular medicine and pathobiology.  It has been formed to provide a framework for recruitment of support for the development of new strategies and applied technologies that require a multidisciplinary approach and hence substantial resources.   Close interaction between investigators of basic and clinical orientation in this hub provide for a comprehensive and efficient scientific approach.  Faculty members of the hub from The Hebrew University and Hadassah include scientists with a strong record in basic research in cardiovascular pathobiology and world renown clinicians in all disciplines of cardiovascular medicine and surgery. 

The following are the principal investigators (in alphabetical order) and their primary areas of research:
Ronen Beeri, MD  (Dept. of Cardiology, Hadassah University Hospital) – Molecular and cellular biology of ventricular myocardial remodeling and effect of mitral regurgitation.  Experimental models of heart diseases.
Muli Ben-Sasson, PhD (
Dept. of cancer Research and Experimental Medicine, IMRIC) – Angiogenic therapies, role of heparin-mimicing compounds and heparin binding compounds in cell proliferation including intimal hyperplasia.
Mottie Chevion, PhD
(Dept. of Cellular Biochemistry, IMRIC) – Ischemic preconditioning, Redox control and iron metabolism in the heart.
Amir Elami, MD
(Dept. of Cardiothoracic Surgery, Hadassah University Hospital) – Novel approaches to valvular surgery, the effect of synthetic cardiac glycoside-like compounds on atrial contractility, novel approach to treatment of diastolic heart failure.
S. David Gertz, MD, PhD (Dept. of Medical Neurobiology [Anatomy], IMRIC) – novel therapeutic strategies for
prevention of the progression of abdominal aortic aneurysm—role of phototherapy; non-invasive imaging technologies for the identification of vulnerable coronary atherosclerotic plaques prone to rupture; the pathogenesis and prevention of in-stent coronary and peripheral arterial stenosis;  alternative treatment strategies for the prevention of sudden death in patients with hypertrophic cardiomyopathy.
Haim Danenberg, MD  (Dept. of Cardiology, Hadassah University Hospital)—Interventional cardiology, predictors of in-stent stenosis, novel therapeutic strategies
Abraham Domb
, PhD, BPh, LLB —(School of Pharmacy, Faculty of Medicine)--Novel advances in biocompatible and biodegradable therapeutic systems, novel drug eluting nanoparticles, resins, and polymers—application to drug eluting stents and other organ systems.
Yechiel Friedlander, MD
– (School of Public Health, Faculty of Medicine)—Genetic epidemiology of cardiovascular diseases and risk factors.
Dan Gilon, MD (Dept. of Cardiology, Hadassah University Hospital) – Non-invasive cardiac imaging including novel strategies for monitoring, diagnosis and treatment.
Gershon Golomb, PhD, BPh (School of Pharmacy, Faculty of Medicine)—Innovative local drug delivery systems, novel strategies using nanoparticles and liposomes, role of bisphosphonates on restenosis.
Michal Horowitz, PhD
(Dept. of Medical Neurobiology [Physiology], IMRIC)-- Heat acclimatory responses in the heart and the hypothalamus
Andre Keren, MD (Department of Cardiology, Hadassah Medical Center) – Novel approaches to the diagnosis and treatment of hypertrophic cardiomyopathy.
Eli Keshet, PhD
(Dept. of Molecular Biology, IMRIC) – Vascular Endothelial Growth Factor (VEGF)—role in development and angiogenesis; vascular manipulations in ischemic heart disease, cardiac muscle hibernation, and cardiac remodeling; angiogenic therapies.
Eran Leitersdorf, MD – (Department of Internal Medicine B, Hadassah University Hospital) Molecular Genetics and treatment of disorders of Lipoprotein metabolism.

David Lichtstein, PhD
(Dept. of Medical Neurobiology [Physiology], IMRIC) – Mechanisms of action and therapeutic actions of cardiac steroids.
Chaim Lotan, MD (Dept. of Cardiology, Hadassah University Hospital)— Interventional cardiology, novel technologies and innovative strategies.
Ehud Razin, PhD
(Dept. of Biochemistry, IMRIC) – Transcription factors in cardiac growth and hypertrophy.
Reuven Reich, PhD (School of Pharmacy, Faculty of Medicine)—molecular and cell biology of extracellular matrix, novel diagnostic and therapeutic strategies.  Role of modification of extracellular matric proteins on the progression of atherosclerotic stenosis and its consequences.
Haim Rosen, PhD (Dept. of Microbiology and Molecular Genetics, IMRIC)--Mechanisms of action and therapeutic actions of cardiac steroids.
Chen Rubenstein, MD (Dept. of Vascular Surgery, Hadassah University Hospital)—novel therapeutic strategies for the treatment of abdominal aortic aneurysm.
Oz M. Shapira, MD (Dept. Cardiothoracic Surgery. Hadassah University Hospital) --Vascular biology,  genetic engineering of vascular grafts, genetic basis of valve and aortic diseases and the role of the immune system in lung cancer -
Shaul Yedgar, PhD (Dept. of Biochemistry, IMRIC)-- Role of phospholipase A2 (PLA2) in inflammtory/allergic processes, and their control by PLA2 inhibition, role of red blood cell flow properties in cardiovascular and inflammatory conditions.
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