Effects of sildenafil and/or muscle derived stem cells on myocardial infarction.
Effects of sildenafil and/or muscle derived stem cells on myocardial infarction.
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DOI：
10.1186/1479-5876-10-159
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发表时间：
2012-08-07
影响因子：
7.4
通讯作者：
Gonzalez-Cadavid NF
中科院分区：
文献类型：
--
作者：
Wang JS;Kovanecz I;Vernet D;Nolazco G;Kopchok GE;Chow SL;White RA;Gonzalez-Cadavid NF
先前的研究表明，长期每日口服pde5抑制剂（PDE5i）可抵消大鼠各种器官组织中的纤维化、细胞损失和由此导致的功能障碍，骨骼肌源性干细胞（MDSC）的植入可发挥其中的一些作用。PDE5i和干细胞联合治疗在非心肌梗死心脏修复中比单独治疗更有效。我们现在研究了低剂量的西地那非和MDSC单独或联合使用是否能有效地减弱大鼠心肌梗死后的左室重构。结扎大鼠左冠状动脉前降支诱导心肌梗死。治疗组分为：“A组”：1)未经治疗；2)口服西地那非3mg /kg/天，从第1天开始；B组：第7天心内注射：3)生理盐水；4)大鼠MDSC（106个细胞）；5)如#4，西地那非如#2。术前、术后1、4周测量左心室射血分数（LVEF）。对左室切片进行胶原、肌成纤维细胞、细胞凋亡、心肌细胞和iNOS染色，然后进行定量图像分析。Western blots通过pde5表达估计血管生成和肌成纤维细胞积累，以及潜在的西地那非快速反应。酶谱法估计血清中MMPs 2和9。与未治疗的心肌梗死大鼠相比，西地那非改善了LVEF，减少了胶原、肌成纤维细胞和循环MMPs，并增加了心肌肌钙蛋白t。MDSC复制了大部分这些作用并刺激了心脏血管生成。同时MDSC/西地那非抵消了心肌细胞和内皮细胞的损失，但没有改善LVEF或血管生成，并上调pde5。长期口服西地那非，或单独给予MDSC，可减轻心肌梗死纤维化瘢痕，改善左心室功能。联合治疗的失败可能是由于诱导PDE5过表达。
Previous studies have shown that long-term oral daily PDE 5 inhibitors (PDE5i) counteract fibrosis, cell loss, and the resulting dysfunction in tissues of various rat organs and that implantation of skeletal muscle-derived stem cells (MDSC) exerts some of these effects. PDE5i and stem cells in combination were found to be more effective in non-MI cardiac repair than each treatment separately. We have now investigated whether sildenafil at lower doses and MDSC, alone or in combination are effective to attenuate LV remodeling after MI in rats. MI was induced in rats by ligature of the left anterior descending coronary artery. Treatment groups were: “Series A”: 1) untreated; 2) oral sildenafil 3 mg/kg/day from day 1; and “Series B”: intracardiac injection at day 7 of: 3) saline; 4) rat MDSC (106 cells); 5) as #4, with sildenafil as in #2. Before surgery, and at 1 and 4 weeks, the left ventricle ejection fraction (LVEF) was measured. LV sections were stained for collagen, myofibroblasts, apoptosis, cardiomyocytes, and iNOS, followed by quantitative image analysis. Western blots estimated angiogenesis and myofibroblast accumulation, as well as potential sildenafil tachyphylaxis by PDE 5 expression. Zymography estimated MMPs 2 and 9 in serum. As compared to untreated MI rats, sildenafil improved LVEF, reduced collagen, myofibroblasts, and circulating MMPs, and increased cardiac troponin T. MDSC replicated most of these effects and stimulated cardiac angiogenesis. Concurrent MDSC/sildenafil counteracted cardiomyocyte and endothelial cells loss, but did not improve LVEF or angiogenesis, and upregulated PDE 5. Long-term oral sildenafil, or MDSC given separately, reduce the MI fibrotic scar and improve left ventricular function in this rat model. The failure of the treatment combination may be due to inducing overexpression of PDE5.
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影响因子：
7.2
作者：
Ho MH;Heydarkhan S;Vernet D;Kovanecz I;Ferrini MG;Bhatia NN;Gonzalez-Cadavid NF
通讯作者：
Gonzalez-Cadavid NF
DOI：
10.1152/ajpheart.00654.2010
发表时间：
2011-06-01
影响因子：
4.8
作者：
Chau, Vinh Q.;Salloum, Fadi N.;Kukreja, Rakesh C.
通讯作者：
Kukreja, Rakesh C.
影响因子：
4.2
作者：
Jeong, Kyung-Hwan;Lee, Tae-Won;Lim, Sung-Jig
通讯作者：
Lim, Sung-Jig
影响因子：
2.6
作者：
Kovanecz, I.;Rambhatla, A.;Gonzalez-Cadavid, N.
通讯作者：
Gonzalez-Cadavid, N.
影响因子：
3.5
作者：
Gonzalez-Cadavid, Nestor F.
通讯作者：
Gonzalez-Cadavid, Nestor F.