Tissue inhibitor of metalloproteinase-2 gene delivery ameliorates postinfarction cardiac remodeling.

Tissue inhibitor of metalloproteinase-2 gene delivery ameliorates postinfarction cardiac remodeling.
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DOI:
10.1111/j.1752-8062.2010.00252.x
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发表时间:
2011-02
期刊:
Clinical and translational science
影响因子:
--
通讯作者:
McTiernan CF
McTiernan CF
中科院分区:
其他
文献类型:
--
作者:
Ramani R;Nilles K;Gibson G;Burkhead B;Mathier M;McNamara D;McTiernan CF

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腺病毒介导(AdV-T2)过表达TIMP-2可以抑制心室重构,提高小鼠慢性缺血性损伤模型的存活率。10-14周龄雄性小鼠(n=124)分别接受1)左冠状动脉结扎诱导心肌梗死(MI组,n=36), 2)心肌梗死后立即注射6×1010 AdV-T2病毒颗粒(MI+T2组,n=30), 3)心肌注射6×1010对照腺病毒颗粒(MI+Ct, n=38),或4)不干预(对照组,n=20)。在心肌梗死后第7天,存活小鼠(n=79)接受超声心动图、免疫组织化学和生化分析。在梗死动物中,心肌梗死+T2组比心肌梗死和心肌梗死+Ct组生存率提高(p< 0.02),较好地保存了已形成的压力和心室直径(p<0.04), MMP-2和MMP-9的表达和活性最低(p<0.04)。所有梗死心脏均显示炎症细胞浸润显著增加(与对照组、心肌梗死组或心肌梗死+T2组相比,p<0.04),心肌梗死+Ct组浸润最高,心肌梗死+T2组浸润最低(p<0.04)。在小鼠心肌梗死模型中,腺病毒介导的TIMP-2基因的心肌传递改善了心肌梗死后的生存并限制了不良重构。
Adenoviral-mediated (AdV-T2) overexpression of TIMP-2 would blunt ventricular remodeling and improve survival in a murine model of chronic ischemic injury. Male mice (n=124) aged 10–14 weeks underwent either 1) left coronary artery ligation to induce myocardial infarction (MI group, n=36), 2) myocardial injection of 6×1010 viral particles of AdV-T2 immediately post-MI (MI+T2 group, n=30), 3) myocardial injection of 6×1010 viral particles of a control adenovirus (MI+Ct, n=38), or 4) received no intervention (controls, n=20). On post-MI day 7, surviving mice (n=79) underwent echocardiographic, immunohistochemical and biochemical analysis. In infarcted animals, the MI+T2 group demonstrated improved survival (p< 0.02), better preservation of developed pressure and ventricular diameter (p<0.04), and the lowest expression and activity of MMP-2 and MMP-9 (P<0.04) compared with MI and MI+Ct groups.. All infarcted hearts displayed significantly increased inflammatory cell infiltration (p<0.04 versus control, MI, or MI+T2), with infiltration highest in the MI+Ct group and lowest in the MI+T2 group (p<0.04). Adenoviral mediated myocardial delivery of the TIMP-2 gene improves post-MI survival and limits adverse remodeling in a murine model of myocardial infarction.
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