Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats.

Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats.
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气管内给予环氧合酶 1 转导的脂肪组织来源的干细胞可改善野百合碱诱导的大鼠肺动脉高压。

DOI:
10.1152/ajpheart.00589.2013
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发表时间:
2014
期刊:
American journal of physiology. Heart and circulatory physiology
影响因子:
--
通讯作者:
Izadpanah,Reza
Izadpanah,Reza
中科院分区:
--
文献类型:
--
作者:
Somanna,NaveenK;Wörner,PhilippM;Murthy,SubramanyamN;Pankey,EdwardA;Schächtele,DeborahJ;StHilaire,Rose-Claire;Jansen,David;Chaffin,AbigailE;Nossaman,BobbyD;Alt,EckhardU;Kadowitz,PhilipJ;Izadpanah,Reza

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研究了大鼠腹腔注射环氧合酶-1(考克斯-1)修饰的脂肪干细胞(ASC)对野百合碱诱导的肺动脉高压(MCT-PH)的影响。从大鼠肠细胞克隆考克斯-1基因,与血凝素(HA)标签融合,并克隆到慢病毒载体中。考克斯-1慢病毒载体显示增强考克斯-1蛋白表达并抑制血管平滑肌细胞增殖而不增加凋亡。用考克斯-1慢病毒载体(ASC考克斯-1)转染的人ASC显示出增强的考克斯-1活性,同时与未转导的(天然)ASC相比显示出相似的分化潜力。用MCT诱导大鼠PH,随后用ASCCOX-1或未转导的ASCs治疗大鼠。当在MCT处理后第35天测量血流动力学值时,在MCT处理后第14天腹腔内给予ASCCOX-13 × 106细胞显著减弱了MCT诱导的PH,而给予未转导的ASC无显著影响。这些结果表明,ASCCOX-1在肺内持续给药至少21天,并减轻MCT诱导的PH和右心室肥大。此外,肺中ASCCOX-1的存在并不改变对一氧化氮供体硝普钠的血管舒张反应。这些数据强调了ASCCOX-1在治疗实验诱导的PH中的有效性。
The effect of intratracheal administration of cyclooxygenase-1 (COX-1)-modified adipose stem cells (ASCs) on monocrotaline-induced pulmonary hypertension (MCT-PH) was investigated in the rat. The COX-1 gene was cloned from rat intestinal cells, fused with a hemagglutanin (HA) tag, and cloned into a lentiviral vector. The COX-1 lentiviral vector was shown to enhance COX-1 protein expression and inhibit proliferation of vascular smooth muscle cells without increasing apoptosis. Human ASCs transfected with the COX-1 lentiviral vector (ASCCOX-1) display enhanced COX-1 activity while exhibiting similar differentiation potential compared with untransduced (native) ASCs. PH was induced in rats with MCT, and the rats were subsequently treated with intratracheal injection of ASCCOX-1or untransduced ASCs. The intratracheal administration of ASCCOX-13 × 106cells onday 14after MCT treatment significantly attenuated MCT-induced PH when hemodynamic values were measured onday 35after MCT treatment whereas administration of untransduced ASCs had no significant effect. These results indicate that intratracheally administered ASCCOX-1persisted for at least 21 days in the lung and attenuate MCT-induced PH and right ventricular hypertrophy. In addition, vasodilator responses to the nitric oxide donor sodium nitroprusside were not altered by the presence of ASCCOX-1in the lung. These data emphasize the effectiveness of ASCCOX-1in the treatment of experimentally induced PH.
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