Tempol inhibits TGF-β and MMPs upregulation and prevents cardiac hypertensive changes
Tempol inhibits TGF-β and MMPs upregulation and prevents cardiac hypertensive changes
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DOI：
10.1016/j.ijcard.2011.08.060
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发表时间：
2013-04-30
影响因子：
3.5
通讯作者：
Gerlach, Raquel F.
中科院分区：
文献类型：
--
作者：
Rizzi, Elen;Castro, Michele M.;Gerlach, Raquel F.
背景资料：氧化应激增加上调基质金属蛋白酶（MMPs）和转化生长因子（TGF-β），它们参与高血压心脏重塑。我们测试了tempol（一种抗氧化剂）可以预防两肾一夹（2K 1C）高血压中这些改变的假设。方法：用tempol（18天（-1）或载体）治疗假手术或高血压大鼠8周。mg.kg每周监测收缩压。在治疗结束时，将导管插入左颈动脉和左心室（LV），以评估动脉血压和收缩功能。在苏木精/伊红切片中进行LV形态测定，并在天狼星红染色切片中评估纤维化。通过免疫荧光法评价心脏TGF-β水平。心脏MMP-2水平和活性测定明胶酶谱法，原位酶谱法，免疫荧光。结果：Tempol可减轻2K 1C诱导的高血压，逆转2K 1C大鼠心肌收缩功能障碍。抗氧化剂治疗可改善心肌肥厚。高血压大鼠心脏MMP-2水平增加，但tempol没有降低MMP-2水平。在未治疗的2K 1C大鼠中发现TGF-β水平、总明胶分解活性和氧化应激增加。Tempol治疗降低氧化应激，TGF-β水平，和明胶分解活性在2K 1C大鼠控制levels.Conclusions：Tempol钝化TGF-β，蛋白水解失衡，和themorphological和功能的改变，发现在2K 1C诱导的心脏肥大的增加。这些发现与抗氧化剂可能有助于预防高血压引起的心脏肥大的观点一致。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Background: Increased oxidative stress upregulates matrix metalloproteinases (MMPs) and transforming grow factor (TGF-beta), which are involved in hypertensive cardiac remodeling. We tested the hypothesis that tempol (an antioxidant) could prevent these alterations in two-kidney, one-clip (2K1C) hypertension.Methods: Sham-operated or hypertensive rats were treated with tempol (18 mg.kg(-1) day(-1) or vehicle) for 8 weeks. Systolic blood pressure was monitored weekly. At the end of the treatment, a catheter was inserted into the left carotid artery and into the left ventricle (LV) to assess arterial blood pressure and contractile function. Morphometry of the LV was carried out in hematoxylin/eosin sections and fibrosis was assessed in picrosirius red-stained sections. Cardiac TGF-beta level was evaluated by immunofluorescence. Cardiac MMP-2 levels and activity were determined by gelatin zymography, in situ zymography, and immunofluorescence. Cardiac superoxide production was evaluated by dihydroethidium probe.Results: Tempol treatment attenuated 2K1C-induced hypertension and reversed the contractile dysfunction in 2K1C rats. Cardiac hypertrophy was ameliorated by antioxidant treatment. Hypertensive rats showed increased cardiac MMP-2 levels, however tempol did not decrease MMP-2 levels. Increased TGF-beta level, total gelatinolytic activity and oxidative stress were found in untreated 2K1C rats. Tempol treatment decreased oxidative stress, TGF-beta levels, and gelatinolytic activity in 2K1C rats to control levels.Conclusions: Tempol blunted the increases in TGF-beta, the proteolytic imbalance, and themorphological and functional alterations found in 2K1C-induced cardiac hypertrophy. These findings are consistent with the idea that antioxidants may help to prevent hypertension-induced cardiac hypertrophy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.