Connective tissue growth factor and cardiac fibrosis after myocardial infarction
Connective tissue growth factor and cardiac fibrosis after myocardial infarction
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DOI：
10.1369/jhc.4a6560.2005
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发表时间：
2005-10-01
影响因子：
3.2
通讯作者：
Burrell, LM
中科院分区：
文献类型：
--
作者：
Dean, RG;Balding, LC;Burrell, LM
研究转化生长因子-β(1)和结缔组织生长因子(CTGF)在有或无血管紧张素转换酶(ACE)抑制的心肌梗死(MI)损伤模型中的时空表达。分别于心肌梗死后1、3、7、28、180天处死大鼠。原位杂交法定位转化生长因子-β(1)、结缔组织生长因子和前胶原α(1)(L)基因，免疫组织化学方法检测转化生长因子-β(1)和结缔组织生长因子蛋白表达。用天狼星红染色法测定胶原蛋白。在另一组中，大鼠接受血管紧张素转换酶抑制剂治疗6个月。心肌梗死后转化生长因子-β(1)、结缔组织生长因子(CTGF)和胶原的表达存在时间和区域差异。心肌梗死后1周，前胶原α1(1)mRNA在交界区和瘢痕中的表达增加，而胶原蛋白在180天内在心脏的所有区域都增加。心肌梗死后1周，交界区和瘢痕组织中转化生长因子-β(1)、mRNA和蛋白的表达均显著增加，达到高峰。心肌梗死后180d，存活心肌CTGF基因和蛋白表达显著增加。长期应用血管紧张素转换酶抑制剂可减少存活心肌的左心室重量和纤维化程度，但对心脏的转化生长因子-β(1)或CTGF无影响。转化生长因子-β(1)参与心肌梗死后炎症和修复的早期、急性期，而结缔组织生长因子参与心脏持续的纤维化。卡托普利的抗肝纤维化作用不是通过降低CTGF来实现的。
The temporal and spatial expression of transforming growth factor (TGF)-beta(1) and connective tissue growth factor (CTGF) was assessed in the left ventricle of a myocardial infarction (MI) model of injury with and without angiotensin-converting enzyme (ACE) inhibition. Coronary artery ligated rats were killed 1, 3, 7, 28, and 180 days after MI. TGF-beta(1), CTGF, and procollagen alpha(1)(l) mRNA were localized by in situ hybridization, and TGF-beta(1), and CTGF protein levels by immunohistochemistry. Collagen protein was measured using picrosirius red staining. In a separate group, rats were treated for 6 months with an ACE inhibitor. There were temporal and regional differences in the expression of TGF-beta(1), CTGF, and collagen after MI. Procollagen alpha 1 (1) mRNA expression increased in the border zone and scar peaking 1 week after MI, whereas collagen protein increased in all areas of the heart over the 180 days. Expression of TGF-beta(1), mRNA and protein showed major increases in the border zone and scar peaking 1 week after MI. The major increases in CTGF mRNA and protein occurred in the viable myocardium at 180 days after MI. Long-term ACE inhibition reduced left ventricular mass and decreased fibrosis in the viable myocardium, but had no effect on cardiac TGF-beta(1), or CTGF. TGF-beta(1), is involved in the initial, acute phase of inflammation and repair after MI, whereas CTGF is involved in the ongoing fibrosis of the heart. The antifibrotic benefits of captopril are not mediated through a reduction in CTGF.