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George S. Abela

Bio: George S. Abela is an academic researcher from Michigan State University. The author has contributed to research in topics: Medicine & Perforation (oil well). The author has an hindex of 41, co-authored 195 publications receiving 9439 citations. Previous affiliations of George S. Abela include University of Florida & Veterans Health Administration.


Papers
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Journal ArticleDOI
29 Apr 2010-Nature
TL;DR: It is shown that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage and 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.
Abstract: 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 inflammation. 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) inflammasome, 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-1alpha/beta-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.

2,904 citations

Journal ArticleDOI
29 Jul 2010-Nature
TL;DR: This corrects the article to show that the method used to derive the H2O2 “spatially aggregating force” is a two-step process, not a single step, like in the previous version of this paper.
Abstract: This corrects the article DOI: 10.1038/nature08938

1,491 citations

Journal ArticleDOI
TL;DR: Researchers believe that onset of myocardial infarction and sudden cardiac death are more likely soon after awakening, indicating that activities of the patient frequentlyTriggering research may clarify mechanisms and suggest measures to sever the linkage between a potential trigger and its pathologic consequence.

448 citations

Journal ArticleDOI
TL;DR: Histologic examination demonstrated that laser radiation produced a wedge incision in the atherosclerotic plaque which was surrounded by zones of thermal and acoustic injury, and the magnitude of injury varied according to the total energy delivered.
Abstract: Laser radiation has been successfully applied in several areas of medical practice. However, its use in cardiology and specifically its effects on obstructive atherosclerosis have largely been unexplored. To evaluate effects of laser radiation on atherosclerotic plaques 25 fresh necropsy atherosclerotic coronary artery segments were exposed to laser radiation with either a carbon dioxide, Nd-YAG, or argon laser. Split or intact segments were prepared under dry conditions or while immersed in saline solution or blood and exposed to laser radiation as power and duration of exposure varied. All 3 lasers were capable of creating controlled injury to atherosclerotic plaques. In general, the magnitude of injury varied according to the total energy delivered (that is, power times duration of exposure. Calcified and noncalcified plaques were penetrated with similar levels of injury. Histologic examination demonstrated that laser radiation produced a wedge incision in the atherosclerotic plaque which was surrounded by zones of thermal and acoustic injury.

327 citations

Patent
20 Feb 1997
TL;DR: In this article, a system and method for percutaneous myocardial revascularization using laser energy emitted from the distal end of a catheter is described, which allows the creation of channels in a patient's heart tissue with the channels having different orientations relative to the proximal end.
Abstract: This invention is a system and method for percutaneous myocardial revascularization using laser energy emitted from the distal end of a catheter. A technique for controlling beam direction allows the creation of channels in a patient's heart tissue with the channels having different orientations relative to the distal end. An arrangement provides for the creation of a plurality of channels at one time by simultaneous application of a plurality of beams of laser energy. A navigation arrangement uses two non-coplanar magnetic sensing coils (124F, 124T, 124S) in the distal end of the catheter cooperating with three sets of three magnetic field generating external coils (i.e., external to the patient) (120F1-120F3, 120S1-120S3, 120T1-120T3). Each of the three sets is sequentially energized and the sensing coils in the distal end sense the magnetic fields established. A computer compares the sensed fields with the known sequence of energizing the external coils and thereby determines the opposition of the distal end. A pressure sensor in the catheter senses ventricular pressure in the patient's heart during and immediately after revascularization.

317 citations


Cited by
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Journal ArticleDOI
TL;DR: Antiinflammatory therapy targeting the interleukin‐1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid‐level lowering.
Abstract: BackgroundExperimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. MethodsWe conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. ResultsAt 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in t...

5,660 citations

Journal ArticleDOI
TL;DR: The ACC and AHA have collaborated with the National Heart, Lung, and Blood Institute and stakeholder and professional organizations to develop guidelines, standards, and policies that promote optimal patient care and cardiovascular health.
Abstract: Preamble and Transition to ACC/AHA Guidelines to Reduce Cardiovascular Risk S50 The goals of the American College of Cardiology (ACC) and the American Heart Association (AHA) are to prevent cardiovascular diseases (CVD); improve the management of people who have these diseases through professional education and research; and develop guidelines, standards, and policies that promote optimal patient care and cardiovascular health. Toward these objectives, the ACC and AHA have collaborated with the National Heart, Lung, and Blood Institute (NHLBI) and stakeholder and professional organizations to develop …

3,524 citations

Journal ArticleDOI
TL;DR: This review will explore potential mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to an unstable and life-threatening atherothrombotic lesion—an event known as plaque fissuring, rupture, or disruption.
Abstract: Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease, and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death.1 2 3 4 5 Therefore, for event-free survival, the vital question is not why atherosclerosis develops but rather why, after years of indolent growth, it suddenly becomes complicated by life-threatening thrombosis. The composition and vulnerability of plaque rather than its volume or the consequent severity of stenosis produced have emerged as being the most important determinants for the development of the thrombus-mediated acute coronary syndromes; lipid-rich and soft plaques are more dangerous than collagen-rich and hard plaques because they are more unstable and rupture-prone and highly thrombogenic after disruption.6 This review will explore potential mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to an unstable and life-threatening atherothrombotic lesion—an event known as plaque fissuring, rupture, or disruption.7 8 Atherosclerosis is the result of a complex interaction between blood elements, disturbed flow, and vessel wall abnormality, involving several pathological processes: inflammation, with increased endothelial permeability, endothelial activation, and monocyte recruitment9 10 11 12 13 14 ; growth, with smooth muscle cell (SMC) proliferation, migration, and matrix synthesis15 16 ; degeneration, with lipid accumulation17 18 ; necrosis, possibly related to the cytotoxic effect of oxidized lipid19 ; calcification/ossification, which may represent an active rather than a dystrophic process20 21 ; and thrombosis, with platelet recruitment and fibrin formation.1 22 23 Thrombotic factors may play a role early during atherogenesis, but a flow-limiting thrombus does not develop until mature plaques are present, which is why thrombosis often is classified as a complication rather than a genuine component of atherosclerosis. ### Mature Plaques: Atherosis and Sclerosis As the name atherosclerosis implies, mature …

3,493 citations

Journal ArticleDOI
19 May 2011-Nature
TL;DR: Understanding how to combine experimental and clinical science will provide further insight into atherosclerosis and could lead to new clinical applications.
Abstract: Atherosclerosis is a chronic disease of the arterial wall, and a leading cause of death and loss of productive life years worldwide. Research into the disease has led to many compelling hypotheses about the pathophysiology of atherosclerotic lesion formation and of complications such as myocardial infarction and stroke. Yet, despite these advances, we still lack definitive evidence to show that processes such as lipoprotein oxidation, inflammation and immunity have a crucial involvement in human atherosclerosis. Experimental atherosclerosis in animals furnishes an important research tool, but extrapolation to humans requires care. Understanding how to combine experimental and clinical science will provide further insight into atherosclerosis and could lead to new clinical applications.

3,214 citations