FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2141350846> ?p ?o ?g. }

• W2141350846 abstract "HomeCirculationVol. 106, No. 22Unraveling the Mechanisms of Plaque Rupture in Murine Models Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBUnraveling the Mechanisms of Plaque Rupture in Murine Models Claudio Napoli, MD and Wulf Palinski, MD Claudio NapoliClaudio Napoli Department of Medicine, University of California San Diego, San Diego, Calif Search for more papers by this author and Wulf PalinskiWulf Palinski Department of Medicine, University of California San Diego, San Diego, Calif Search for more papers by this author Originally published26 Nov 2002https://doi.org/10.1161/01.CIR.0000037299.57776.45Circulation. 2002;106:e186To the Editor:Mice are rapidly becoming a model of choice for atherosclerosis and coagulation-related studies, but the suitability of murine models with extensive atherosclerosis for the interphase of these two processes, ie, plaque rupture and intramural thrombosis, remains controversial.1 Plaque ruptures and spontaneous erosions reaching the core of atheromas occur spontaneously, but rather infrequently, in a variety of murine arteries.2,3 In their recent article, von der Thüsen and colleagues4 utilized a combination of a perivascular collar, transfection with the proapoptotic factor p53, and acute phenylephedrine-induced stress to achieve a high frequency of rupture in the carotid artery. However, the accompanying editorial from Dr Majesky emphasizes the absence of fibrin-rich clots and questions whether this is a valid model of human plaque rupture. We believe that the requirement of a murine model to faithfully reflect human plaque rupture is counterproductive. Although fibrin-rich thrombi do occur in mice,3 fundamental differences between mice and men exist in hemodynamic conditions, anatomy of normal arteries, composition of atherosclerotic lesions, mechanical properties, and degrees of stenosis. In humans, approximately 2/3 of acute coronary syndromes evolve from plaques that are mildly obstructive before the acute event. In contrast, even early stages of murine lesions are associated with substantial stenosis and hemodynamic alterations that may influence rupture and thrombus formation. Two pathomechanistic differences appear particularly important: (1) murine atherosclerosis has a far greater propensity to invade the media; and (2) murine atheromas frequently show multiple superimposed smooth muscle caps3 that may be particularly prone to—or be the result of—deep erosion or rupture. A report of frequent spontaneous rupture of such plaques in the brachiocephalic artery also highlights important regional differences.5 Despite these differences, substantial similarities exist between murine models and humans and valuable insights may be gained by modulating specific factors influencing inflammation and plaque stability, as von der Thüsen et al demonstrated. References 1 Palinski W, Napoli C. Unraveling pleiotropic effects of statins on plaque rupture. Arterioscler Thromb Vasc Biol. 2002; 22: 1745–1750.LinkGoogle Scholar2 Johnson JL, Jackson CL. Atherosclerotic plaque rupture in the apolipoprotein E knockout mouse. Atherosclerosis. 2001; 154: 399–406.CrossrefMedlineGoogle Scholar3 Calara F, Silvestre M, Casanada F, et al. Spontaneous plaque rupture and secondary thrombosis in apolipoprotein E-deficient and LDL receptor-deficient mice. J Pathol. 2001; 195: 257–263.CrossrefMedlineGoogle Scholar4 von der Thüsen JH, van Vlijmen BJ, Hoeben RC, et al. Induction of atherosclerotic plaque rupture in apolipoprotein E−/− mice after adenovirus-mediated transfer of p53. Circulation. 2002; 105: 2064–2070.LinkGoogle Scholar5 Williams H, Johnson JL, Carson KGS, et al. Characteristics of intact and ruptured atherosclerotic plaques in brachiocephalic arteries of apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol. 2002; 22: 788–792.LinkGoogle ScholarcirculationahaCirculationCirculationCirculation0009-73221524-4539Lippincott Williams & WilkinsResponsevon der Thüsen Jan H., , MD, PhD, van Berkel Theo J.C., , PhD, Biessen Erik A.L., , PhD, Hoeben Rob C., , PhD, van Vlijmen Bart J.M., , PhD, Havekes Louis M., , PhD, and Kockx Mark M., , MD, PhD26112002We wish to thank Drs Napoli and Palinski for their appraisal of our recent study and for their qualification of some of the criticisms put forward in the editorial of Dr Majesky.1 We fully concur with their opinion that progress in the design of new murine substrates for therapeutic and mechanistic studies on plaque rupture will not be aided by demanding that human thrombotic rupture be accurately reproduced. In view of its high clinical relevance, there is an urgent need for adequate animal models for thrombotic rupture. As also pointed out by Dr Bennett in a recent editorial in Arteriosclerosis, Thrombosis, and Vascular Biology,2 this new testing ground for therapeutics that intervene in plaque rupture should ideally be “a model of acute synchronous and reproducible rupture in a large portion of treated animals.” Although we do realize that several specific phenomena associated with thrombotic plaque rupture in humans are absent in the p53 model (eg, lack of fibrin-rich lesions), grosso modo it meets these criteria.3 Moreover, thrombotic rupture is widely considered a 3-step process involving plaque destabilization, a biomechanical trigger to incite cap rupture, and an intramural procoagulant milieu. Also in this respect, the p53 model essentially mirrors the current paradigm. We agree with Dr Majesky that the potential of the p53 model for high throughput screening will indeed be limited, but this was not the major motivation for its development. Although far from optimal, we consider the present model with its rapid development time, accessibility of lesions, high incidence of events, and temporal/spatial control already useful for mechanistic and therapeutic studies. In addition, new studies are underway to further enhance the physiological relevance of the individual steps required to achieve plaque rupture in this model. For instance, the use of strong triggers with prolonged vasopressor activity may require further improvement and we consider more physiological stressors, like hypoxic or mental stress,4 intracranial ACTH injection, or IV epinephrine injection as possible options in this regard. Apart from validating the pros and cons of the p53 model, the mere finding that p53 overexpression destabilizes plaques may hold the key to delineating one of the pathways in the plaque destabilization process in humans and thus possibly to paving the way for new therapeutic entries to prevent this process. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Hotchi J, Hoshiga M, Takeda Y, Yuki T, Fujisaka T, Ishihara T and Hanafusa T (2013) Plaque-Stabilizing Effect of Angiotensin-Converting Enzyme Inhibitor and/or Angiotensin Receptor Blocker in a Rabbit Plaque Model, Journal of Atherosclerosis and Thrombosis, 10.5551/jat.14266, 20:3, (257-266), . Okabe T, Hoshiga M, Negoro N, Nakakoji T, Arishiro K, Ishihara T, Ueno H and Hanafusa T (2011) Rabbit plaque models closely resembling lesions in human coronary artery disease, International Journal of Cardiology, 10.1016/j.ijcard.2009.09.528, 147:2, (271-277), Online publication date: 1-Mar-2011. Mehta J, Hu B, Chen J and Li D (2003) Pioglitazone Inhibits LOX-1 Expression in Human Coronary Artery Endothelial Cells by Reducing Intracellular Superoxide Radical Generation, Arteriosclerosis, Thrombosis, and Vascular Biology, 23:12, (2203-2208), Online publication date: 1-Dec-2003. November 26, 2002Vol 106, Issue 22 Advertisement Article InformationMetrics https://doi.org/10.1161/01.CIR.0000037299.57776.45PMID: 12451021 Originally publishedNovember 26, 2002 PDF download Advertisement" @default.
• W2141350846 created "2016-06-24" @default.
• W2141350846 creator A5049658448 @default.
• W2141350846 creator A5061269136 @default.
• W2141350846 date "2002-11-26" @default.
• W2141350846 modified "2023-09-27" @default.
• W2141350846 title "Unraveling the Mechanisms of Plaque Rupture in Murine Models" @default.
• W2141350846 cites W2037525025 @default.
• W2141350846 cites W2060671236 @default.
• W2141350846 cites W2091661866 @default.
• W2141350846 cites W2119352838 @default.
• W2141350846 cites W2122574397 @default.
• W2141350846 cites W2124927788 @default.
• W2141350846 cites W2128505096 @default.
• W2141350846 cites W2142198314 @default.
• W2141350846 doi "https://doi.org/10.1161/01.cir.0000037299.57776.45" @default.
• W2141350846 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12451021" @default.
• W2141350846 hasPublicationYear "2002" @default.
• W2141350846 type Work @default.
• W2141350846 sameAs 2141350846 @default.
• W2141350846 citedByCount "3" @default.
• W2141350846 countsByYear W21413508462013 @default.
• W2141350846 crossrefType "journal-article" @default.
• W2141350846 hasAuthorship W2141350846A5049658448 @default.
• W2141350846 hasAuthorship W2141350846A5061269136 @default.
• W2141350846 hasConcept C164705383 @default.
• W2141350846 hasConcept C2778710248 @default.
• W2141350846 hasConcept C71924100 @default.
• W2141350846 hasConceptScore W2141350846C164705383 @default.
• W2141350846 hasConceptScore W2141350846C2778710248 @default.
• W2141350846 hasConceptScore W2141350846C71924100 @default.
• W2141350846 hasIssue "22" @default.
• W2141350846 hasLocation W21413508461 @default.
• W2141350846 hasLocation W21413508462 @default.
• W2141350846 hasOpenAccess W2141350846 @default.
• W2141350846 hasPrimaryLocation W21413508461 @default.
• W2141350846 hasRelatedWork W1506200166 @default.
• W2141350846 hasRelatedWork W1995515455 @default.
• W2141350846 hasRelatedWork W2039318446 @default.
• W2141350846 hasRelatedWork W2048182022 @default.
• W2141350846 hasRelatedWork W2080531066 @default.
• W2141350846 hasRelatedWork W2748952813 @default.
• W2141350846 hasRelatedWork W2899084033 @default.
• W2141350846 hasRelatedWork W3031052312 @default.
• W2141350846 hasRelatedWork W3032375762 @default.
• W2141350846 hasRelatedWork W3108674512 @default.
• W2141350846 hasVolume "106" @default.
• W2141350846 isParatext "false" @default.
• W2141350846 isRetracted "false" @default.
• W2141350846 magId "2141350846" @default.
• W2141350846 workType "article" @default.