Professor
Principal investigator, Cardiovascular Research Laboratory, Department of Medical Neurobiology
Head, Saul and Joyce Brandman Cardiovascular Research Hub, Institute for Medical Research – Israel Canada, Faculty of Medicine, The Hebrew University of Jerusalem
Director, Institute for Research in Military Medicine (IRMM), Faculty of Medicine, The Hebrew University and IDF Medical Corps
The Saul and Joyce Brandman Cardiovascular Research Hub has been established to provide a centralized framework for scientific collaboration to address the major problems in cardiovascular medicine and pathobiology. It has been formed to provide a path 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 provides for a comprehensive and efficient scientific approach. Faculty members of the hub from The Hebrew University and Hadassah include scientists with strong records in basic cellular and molecular research in cardiovascular pathobiology and world renown clinician investigators in all disciplines of cardiovascular medicine and surgery. (additional details on request)
Current projects in our laboratory include:
Additional projects in our laboratory include:
Institute for Research in Military Medicine (IRMM) of The Hebrew University Faculty of Medicine and the IDF Medical Corps:
The IRMM, by combining the best of human resources and materiel from academia, clinical medicine, and the operational arena provides a unique research and development framework in military medicine whose principal objective is to prolong survival, hasten recovery, and improve quality of life of our soldiers and civilians in times of peace or during hostilities. The mission of the IRMM is the development of novel treatments and technologies of relevance to operational medicine. Current projects include (but are not limited to):
Gavish, L., Gilon, D., Beeri, R., Zuckerman, A., Nachman, D., and Gertz, S.D.: Photobiomodulation and Estrogen Stabilize Mitochondrial Membrane Potential in Angiotensin-II Challenged Porcine Aortic Smooth Muscle Cells: Relevance to Abdominal Aortic Aneurysm in Women. Journal of Biophotonics, 2021 Jan;14(1):e202000329. doi: 10.1002/jbio.202000329. Epub 2020 Sep 21.PMID: 32888351.
Rupture of Abdominal aortic aneurysm (AAA) is among the 15 leading causes of death after age 65. Using high frequency ultrasound, we showed that photobiomodulation (PBM) prevents formation and progression of AAA in the angiotensin-II (Ang-II)-infused, apolipoprotein-e-deficient mouse model. In the current study we report that while challenge of porcine aortic Smooth Muscle Cells (SMCs) with Ang-II (1 μM) resulted in a marked decay in mitochondrial membrane potential (MitMP) vs non-challenged cells, treatment with PBM (continuous diode laser, 780 nm, 6.7 mW/cm2 , 5 minutes, 2 J/cm2 ) or pre-incubation with estrogen (50 nM, 1 hour) significantly attenuated this deterioration in MitMP. We also report that PBM and estrogen markedly affected porcine aortic SMC contraction and modified mitochondrial dispersion reflecting important influence on SMC function. These studies provide strong evidence of the important underlying role of mitochondria in the preventive effect of PBM on formation and progression of AAA and its reduced incidence and delayed onset in women.
Yaniv, G., Eisenkraft, A., Gavish, L., Wagnert-Avraham, L., Nachman, D., Megreli, J., Shimon, G., Rimbrot, D., Simon, B., Berman, A., Cohen, M., Kushnir, D., Shaylor, R., Firman, S., Shlaifer, A., Hartal, M., Heled, Y., Glassberg, E., Kreiss, Y., and Gertz, S.D. Remote Ischemic Preconditioning Improves Tissue Oxygenation in a Porcine Model of Controlled Hemorrhage Without Fluid Resuscitation. Scientific Reports (Nature Group) 2021 May 24;11(1):10808. doi: 10.1038/s41598-021-90470-6. PMID: 34031524.
In a previous study of controlled hemorrhagic shock in a large animal (porcine) model, we reported that maladaptive responses across a range of cardiovascular parameters that begin early after hemorrhage may be predictive of impending death, particularly in situations where early resuscitative treatment may be delayed. The current study was designed to test the effect of limb RIPC on survival, as well as a broad range of hemodynamic and biochemical parameters, in this large animal model of controlled hemorrhage, without fluid return or replacement therapy, simulating that which may occur in extreme field situations involving several hours of delayed evacuation and definitive medical care.
Gavish, L., Beeri, R., Gilon, D., Rubinstein, C., Berlatzky, Y., Gavish, L.Y., Bulut, A., Harlev, M., Reissman, P., and Gertz, S.D.: Inadequate Reinforcement of Transmural Disruptions at Branch Points Subtends Aortic Aneurysm Formation In Apolipoprotein-E-Deficient Mice. Cardiovascular Pathology, 23(3):152-159, 2014.
Recent in vitro studies by our group indicated that low level laser irradiation (LLLI) modifies cellular processes essential to the progression of abdominal aortic aneurysm (AAA). Using high-frequency ultrasonography (HF-u/s) in the angiotensin-II (Ang-II)-infused, apolipoprotein-E-deficient (Apo-E−/−) mouse model of AAA, we found that LLLI markedly inhibited aneurysm formation and preserved arterial wall elasticity. We now report, using quantitative histopathology, the likely mechanism underlying the preventative effect of LLLI on aneurysm formation in this model.
Gavish, L., Rubinstein, C., Bulut, A., Berlatzky, Y., Beeri, R., Gilon, D., Gavish, L., Harlev, M., Reissman, P., and Gertz, S.D.: Low Level Laser Irradiation Inhibits Abdominal Aortic Aneurysm Progression in Apolipoprotein E-Deficient Mice (High-Frequency Ultrasound Studies). Cardiovascular Research, 83(4):785-92, 2009.
Increased early detection of abdominal aortic aneurysm (AAA) and the severe complications of its current treatment have emphasized the need for alternative therapeutic strategies that target pathogenetic mechanisms of progression and rupture. Recent in vitro studies from our laboratory have shown that low-level laser irradiation (LLLI) (780 nm) modifies cellular processes fundamental to aneurysm progression. The present study was designed to determine whether LLLI retards the progression of suprarenal AAA in vivo.
Gertz, S.D., Bodmann, B.G, Vela, D., Papadakis, M., Aboshady, I., Cherukuri, P., Alexander, S., Kouri, D., Baid, S., Gittens, A.A., Gladish, G., Conyers, J.L., Cody, D.D., Gavish, L., Mazraeshahi, R.M., Wilner, W.T, Frazier, L., Lukovenkov, S., Madjid, M., Zarrabi, A., Ahmed, A., Willerson, J.T., and Casscells, S.W.: Three-Dimensional Isotropic Wavelet Analysis for Post-Acquisitional Extraction of Latent Images of Atherosclerotic Plaque Components from Micro-Computed Tomography of Human Coronary Arteries. Academic Radiology, 14(12):1509-1519, 2007.
The capability of wavelet transforms to separate signals into frequency bands is the basis for its use in image compression and storage, data management and transmission, and, recently, extraction of latent images of tissue components from noisy medical images. Analysis of temporal variations of radiofrequency backscatter of intravascular ultrasound with one-dimensional wavelets can detect lipid-laden plaque in coronary arteries with a sensitivity and specificity of >80%. In this study we evaluate the capability of a novel, 3-dimensional isotropic wavelet analysis to perform high resolution, non-directionally biased, statistically reliable, non-invasive discrimination between components of human coronary atherosclerotic plaques in micro-CT.
Gertz, S.D., Barry, W.L., Gimple, L.W., Banai, S., Perez, L.S., McNamara, C.A., Powers, E.R., Ragosta M., Owens, G.K., Roberts, W.C., and Sarembock, I.J.: Predictors of Luminal Narrowing by Neointima after Angioplasty in Atherosclerotic Rabbits. Cardiovascular Research, 36(3):396-407, 1997.
These studies show that neointimal formation contributes significantly to luminal narrowing 1 month after angioplasty in this model, that the degree of vascular injury and the extent of foam cell accumulation in the neointima and media are significant independent predictors of neointimal formation, and that the area of the neointima, and the percent narrowing by neointima, are important predictors of remodeling itself (EEL area). These predictors were not identifiable when the analysis was focused on the determinants of absolute luminal area alone.
Ragosta, M., Gimple, L.W., Gertz, S.D., Dunwiddie, C.T., Haber, H.L., DiFrancisco, J., Powers, E.R., Roberts, W.C., and Sarembock, I.J.: Specific Factor Xa Inhibition Reduces Restenosis Following Balloon Angioplasty of Atherosclerotic Femoral Arteries in Rabbits. Circulation 89(3): 1262-1271, 1994.
Balloon angioplasty of atherosclerotic arteries results in activation of the coagulation cascade. Several coagulation factors, including factor Xa and thrombin, are mitogenic for vascular smooth muscle cells in vitro and thus may play a role in restenosis after balloon angioplasty. Specific inhibition of factor Xa can be achieved with recombinant antistasin (rATS) or tick anticoagulant peptide (rTAP). We hypothesized that inhibition of Xa would limit restenosis after balloon angioplasty in an atherosclerotic rabbit model.
Gertz, S.D., Kragel, A.H., Kalan, J.M., Braunwald, E., Roberts, W.C., and The Thrombolysis in Myocardial Infarction (TIMI) Investigators: Comparison of Coronary and Myocardial Morphologic Findings in Patients with and without Thrombolytic Therapy During First Fatal Acute Myocardial Infarction. American Journal of Cardiology. 66: 904-909, 1990.
The hearts of 61 patients (39 men aged 64 ± 11 years) who died from 5 hours to 42 days (median 3 days) after a fatal first acute myocardial infarction without having undergone percutaneous transluminal coronary angioplasty or coronary bypass surgery were studied to compare clinical and cardiac morphologic features of patients receiving thrombolytic therapy with tissue-plasminogen activator (t-PA) to those not receiving thrombolytic therapy. Comparison of findings in the 23 patients who received t-PA intravenously 3 ± 1 hours after onset of symptoms, with the 38 patients who did not, showed similar baseline characteristics with respect to: age, gender, history of hypertension; location of the infarct; heart weight; severity and numbers of coronary arteries narrowed; and frequencies of plaque rupture, plaque hemorrhage and coronary thrombi. Among the patients receiving t-PA, however, there was a greater frequency of platelet-rich (fibrin-poor) thrombi in the infarct-related coronary arteries (6 of 11 vs 4 of 25 thrombi; p = 0.02), more nonocclusive than occlusive thrombi (6 of 11 vs 4 of 25 thrombi; p = 0.02), and a lower frequency of myocardial rupture (left ventricular free wall or ventricular septum) (5 of 23 [22%] vs 18 of 38 [46%]; p = 0.045).
Gertz, S.D., Kurgan, A., and Eisenberg, D.: Aneurysm of the Rabbit Common Carotid Artery Induced by Periarterial Application of Calcium Chloride. Journal of Clinical Investigation, 81:649-656, 1988.
Experimental aneurysmatic dilatation of the rabbit common carotid artery was induced by a single, periarterial application of calcium chloride in vivo. Progressive focal aneurysmal dilatation was seen limited to the site of calcium application with endothelial damage and thrombus formation in areas of irregular luminal contour. Disruption of the elastic network of the intima and media was seen with varying degrees of intimal fibromuscular hyperplasia and medial disorganization. The calcium-elastic tissue complex was the focus of the inflammatory, arteriosclerotic reaction and subsequent aneurysm formation. The inflammatory cell infiltration initially included primarily neutrophils followed by lymphocytes, plasma cells, monocytes, and multinucleated giant cells. These studies support the hypothesis that disruption of the elastic tissue network of the vascular wall represents an important pathogenetic factor in the initiation of aneurysmal dilatation. In addition, the results of these studies suggest that interaction of calcium with the elastica of the arterial wall may represent an important pathogenetic factor in the initiation of giant cell arteritis.
Gertz, S.D., Uretzky, G., Wajnberg, R.S., Navot,N., and Gotsman, M.S.: Endothelial Cell Damage and Thrombus Formation Following Partial Arterial Constriction: Relevance to the Role of Coronary Artery Spasm in the Pathogenesis of Myocardial Infarction. Circulation 63:476-486,1981.
The left anterior descending coronary artery of four dogs and the right common carotid artery of 15 rabbits were subjected to 40-60% reduction in transluminal diameter for 1 hour by partial ligation with suture thread. Scanning electron microscopic examination of the luminal surface of these vessels revealed endothelial craters and balloons, fragmentation and desquamation on the proximal slope of the constriction. Platelet attachment to exposed subendothelial tissues was clearly evident, and microthrombi were seen at the point of maximum constriction. Blood flow, as measured by electromagnetic flow probe, was virtually unchanged upon partial ligation. In control studies, where a second ligature was placed proximal to and before the first to reduce blood flow to the distal constriction site substantially or totally, endothelial desquamation was found in only one of 14 animals, and the number of craters and balloons was significantly reduced. We suggest that endothelial damage and thrombus formation may occur at the site of focal arterial constriction even when the reduction in transluminal diameter is insufficient to alter substantially the rate of flow.
BA, Yeshiva University, New York
MSc, The University of Maryland at Baltimore
PhD, The University of Maryland at Baltimore
Post-Doctoral Fellowship: Department of Neurology, The University of Maryland at Baltimore
MD, The Hebrew University-Hadassah Medical School; 1988
Internship, Shaare Zedek Hospital; 1988
Cardiovascular Pathology, Senior Staff Fellowship: Pathology Branch, National Heart, Lung and BIood Institute, National Institutes of Health, Bethesda, MD; 1988-1990.
Lieutenant Colonel (Res.), IDF Medical Corps; currently serving as the Advisor to the IDF Surgeon General for Victim Identification, and previously as Deputy Commander of the Forensic Identification Unit.
Professor of Anatomy and Cell Biology; Full Professor, 1998
The Brandman Foundation Professor of Cardiac and Pulmonary Diseases, Faculty of Medicine, HUJI; 2009-pres.
Chairman, Department of Anatomy and Cell Biology, The Hebrew University—Hadassah Medical School; 1990-1994, 1998-2002.
Head, The Saul and Joyce Brandman Cardiovascular Research Hub, Institute for Medical Research (IMRIC), Faculty of Medicine, HUJI; 2010-pres.
