George Abela is a clinician-scientist who treats patients with heart disease and conducts research. His work has demonstrated for the first time the underlying mechanism of how cholesterol expands in volume when crystalizing and tears up the arterial wall causing heart attacks.
Abela is a professor of cardiology and chief of the Division of Cardiology at MSU. He is also program director for the Cardiovascular Fellowship Training Program.
He is a fellow of the American College of Cardiology, National Lipid Association and the American Heart
Association. He has authored numerous manuscripts on the effects of cholesterol crystals and plaque rupture and has been a reviewer for major cardiovascular journals.
Industry Expertise (4)
Areas of Expertise (4)
Mid-West Lipid Association Award (professional)
Recognizes the excellence, innovation and leadership of healthcare professionals in the NLA with respect to clinical lipidology in private practice or academic settings.
American University of Beirut: MD, Medicine 1976
- American Board of Internal Medicine
- Institute for Prevention of Cardiovascular Disease at Harvard Medical School
Cholesterol Crystals Are Sure Sign a Heart Attack May Loom
MSU Today print
"George Abela, lead author and chief cardiologist at MSU, analyzed the material that was obstructing the coronary arteries of patients who had suffered a heart attack and found that 89 percent of them had an excessive amount of these crystallized structures, referred to as cholesterol crystals..."
Journal Articles (3)
Janoudi A, Shamoun FE, Kalavakunta JK, Abela GS.
Evolution of plaque that is prone to rupture is characterized by inflammation and physical changes. Accumulation of low-density lipoprotein in the sub-intima provides esterified cholesterol (ESC) to macrophages and smooth muscle cells that convert it into free cholesterol (FRC) by cholesteryl ester hydrolases (CEHs). Membrane-bound cholesterol carriers transport FRC to high-density lipoprotein (HDL). Impaired HDL transport function and altered composition can lead to extracellular accumulation of FRC, whereas impaired membrane carrier activity can lead to intracellular FRC accumulation. Saturation of FRC can result in cholesterol crystallization with cell death and intimal injury. Disequilibrium between ESC and FRC can impact foam cell and cholesterol crystal (CC) formation. Cholesterol crystals initiate inflammation via NLRP3 inflammasome leading to interleukin-1β (IL-1β) production inducing C-reactive protein. Eventually, crystals growing from within the plaque and associated inflammation destabilize the plaque. Thus, inhibition of inflammation by antagonists to IL-1β or agents that dissolve or prevent CC formation may stabilize vulnerable plaques.
Peter Duewell, Hajime Kono, Katey J. Rayner, Cherilyn M. Sirois, Gregory Vladimer, Franz G. Bauernfeind, George S. Abela, Luigi Franchi, Gabriel Nuñez, Max Schnurr, Terje Espevik, Egil Lien, Katherine A. Fitzgerald, Kenneth L. Rock, Kathryn J. Moore, Samuel D. Wright, Veit Hornung & Eicke Latz
The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to atherosclerosis, suggesting that endogenous substances initiate the inflammation1. Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance late in atherogenesis had been thought to disqualify them as primary inflammatory stimuli. However, using a new microscopic technique, we revealed that minute cholesterol crystals are present in early diet-induced atherosclerotic lesions and that their appearance in mice coincides with the first appearance of inflammatory cells. Other crystalline substances can induce inflammation by stimulating the caspase-1-activating NLRP3 (NALP3 or cryopyrin) inflammasome2,3, which results in cleavage and secretion of interleukin (IL)-1 family cytokines. Here we show that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage. Similarly, when injected intraperitoneally, cholesterol crystals induce acute inflammation, which is impaired in mice deficient in components of the NLRP3 inflammasome, cathepsin B, cathepsin L or IL-1 molecules. Moreover, when mice deficient in low-density lipoprotein receptor (LDLR) were bone-marrow transplanted with NLRP3-deficient, ASC (also known as PYCARD)-deficient or IL-1α/β-deficient bone marrow and fed on a high-cholesterol diet, they had markedly decreased early atherosclerosis and inflammasome-dependent IL-18 levels. Minimally modified LDL can lead to cholesterol crystallization concomitant with NLRP3 inflammasome priming and activation in macrophages. Although there is the possibility that oxidized LDL activates the NLRP3 inflammasome in vivo, our results demonstrate that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. These findings provide new insights into the pathogenesis of atherosclerosis and indicate new potential molecular targets for the therapy of this disease.
Atul Khasnis, Krit Jongnarangsin, George Abela, Srikar Veerareddy, Vivek Reddy, Ranjan Thakur