کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5842892 1560681 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vivo gene delivery of XIAP protects against myocardial apoptosis and infarction following ischemia/reperfusion in conscious rabbits
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
In vivo gene delivery of XIAP protects against myocardial apoptosis and infarction following ischemia/reperfusion in conscious rabbits
چکیده انگلیسی

AimsWe tested the hypothesis that an in vivo gene delivery of the pro-survival protein XIAP (X-chromosome linked inhibitor of apoptosis protein) protects against myocardial apoptosis and infarction following ischemia/reperfusion.Main methodsNineteen rabbits were chronically instrumented with a hydraulic occluder placed around the circumflex coronary artery. Adenovirus harboring XIAP (Ad.XIAP; 1 × 1010 pfu/ml) or β-galactosidase (5 × 109 pfu/ml), as a control, was constructed and transfected into the heart using a catheter placed into the left ventricle accompanied by cross-clamping. 1-2 weeks after gene delivery, myocardial ischemia was induced by a 30-min occlusion followed by reperfusion for four days. Protein expression was determined by Western blot and apoptosis (% of myocytes) was quantified by TUNEL staining.Key findingsMyocardial infarct size, expressed as a fraction of the area at risk, was reduced in Ad.XIAP (n = 5) compared to control (n = 7) rabbits (21 ± 3% vs. 30 ± 2%, p < 0.05). Apoptosis was reduced in Ad.XIAP rabbits compared to control rabbits (2.96 ± 0.68% vs. 8.98 ± 1.84%, p < 0.01). This was associated with an approximate 60% decrease in the cleaved caspase-3 level in Ad.XIAP rabbits compared to control rabbits.SignificanceThe current findings demonstrate that overexpression of XIAP via in vivo delivery in an adenovirus can reduce both myocardial apoptosis and infarction following ischemia/reperfusion, at least in part, due to the ability of XIAP to inhibit caspase-3. These findings confirm previous work suggesting a link between myocardial apoptosis and infarction i.e., anti-apoptotic therapy was effective in reducing myocardial infarct size.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 88, Issues 13–14, 28 March 2011, Pages 572-577
نویسندگان
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