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Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis

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dc.creator Ibáñez, Borja
dc.creator Vilahur, Gemma
dc.creator Cimmino, Giovanni
dc.creator Speidl, Walter S.
dc.creator Piñero, Antonio
dc.creator Choi, Brian G.
dc.creator Zafar, M. Urooj
dc.creator Santos-Gallego, Carlos G.
dc.creator Krause, Brian
dc.creator Badimón, Lina
dc.creator Fuster, Valentín
dc.creator Badimón, Juan José
dc.date 2008-05-09T14:15:28Z
dc.date 2008-05-09T14:15:28Z
dc.date 2008-03-18
dc.date.accessioned 2017-01-31T01:13:40Z
dc.date.available 2017-01-31T01:13:40Z
dc.identifier J Am Coll Cardiol. 51(11): 1104-1109 (2008).
dc.identifier 0735-1097
dc.identifier http://hdl.handle.net/10261/4129
dc.identifier 10.1016/j.jacc.2007.09.071
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/4129
dc.description PMID: 18342230
dc.description A correction to this paper regarding a mistaken figure was published in: Journal of the American College of Cardiology, Volume 51, Issue 15, 15 April 2008, Page 1525.
dc.description [Objectives] This study sought to assess the effect of short-term apolipoprotein (apo) A-I(Milano) administration on plaque size and on suspected markers of plaque vulnerability.
dc.description [Background] Long-term lipid-lowering interventions can regress and stabilize atherosclerotic plaques. However, the majority of recurrent events occur early after the first episode. Interventions able to acutely induce plaque regression and stabilization are lacking. Regression of human coronary lesions after 5 weeks of treatment with apoA-I(Milano) administration has been shown. However, there are no data regarding its effect on plaque vulnerability.
dc.description [Methods] Advanced aortic lesions were induced in New Zealand White rabbits (n = 40). Plaque size was assessed by magnetic resonance imaging (MRI) at the end of atherosclerosis induction. Animals were randomized to placebo or apoA-I(Milano) phospholipids (ETC-216), 2 infusions 4 days apart. After the last dose, another MRI study was performed and aortas were processed for cellular composition and gene protein expression of markers associated with plaque instability.
dc.description [Results] Pre-treatment MRI showed similar plaque size in both groups, whereas post-treatment MRI showed 6% smaller plaques in apoA-I(Milano)-treated animals compared with placebo (p = 0.026). The apoA-I(Milano) treatment induced a 5% plaque regression (p = 0.003 vs. pre-treatment), whereas the placebo showed no significant effect. Plaque regression by apoA-I(Milano) was associated with a reduction in plaque macrophage density and a significant down-regulation in gene and protein expression of tissue factor, monocyte chemoattractant protein-1, and cyclooxygenase-2, as well as marked decrease in gelatinolytic activity. Conversely, cyclooxygenase-1 was significantly up-regulated.
dc.description [Conclusions] Acute plaque regression observed after short-term apoA-I(Milano) administration was associated with a significant reduction in suspected makers of plaque vulnerability in an experimental model of atherosclerosis.
dc.description This work has been partially funded by Pfizer Research & Development. Dr. Ibáñez has received a grant from the Working Group on Ischemic Heart Disease of the Spanish Society of Cardiology. Dr. Vilahur has received a grant from the Science-Education Spanish Ministry. Dr. Badimón has served as a consultant for Pfizer.
dc.description Peer reviewed
dc.format 22195 bytes
dc.format application/pdf
dc.language eng
dc.publisher Elsevier
dc.relation http://dx.doi.org/10.1016/j.jacc.2007.09.071
dc.rights closedAccess
dc.subject Apolipoprotein (apo) A-I(Milano)
dc.subject Atherosclerotic plaques
dc.subject Plaque regression
dc.title Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis
dc.type Artículo


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