Overexpression of brain natriuretic peptide facilitates neutrophil infiltration and cardiac matrix metalloproteinase-9 expression after acute myocardial infarction
Overexpression of brain natriuretic peptide facilitates neutrophil infiltration and cardiac matrix metalloproteinase-9 expression after acute myocardial infarction
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DOI：
10.1161/01.cir.0000147829.78357.c5
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发表时间：
2004-11-23
期刊：
影响因子：
37.8
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Kawakami, R;Saito, Y;Nakao, K
背景-最近的临床试验表明，全身输注奈西立肽（一种重组人脑利钠肽（BNP））可改善急性失代偿心脏的血流动力学参数。这表明，BNP发挥直接的心脏保护作用，因此可能是一个有用的治疗剂，其中治疗急性心肌梗死（MI）。在本研究中，我们使用BNP转基因（BNP-Tg）小鼠血浆BNP水平升高，以确定是否以及如何BNP有助于左心室重塑和愈合后MI.Methods和结果，我们研究了中性粒细胞的积累和表达和激活的基质金属蛋白酶（MMP）-9（ventricles of male BNP-Tg mice and their non-transgenic（non-Tg）litmates during the early phase after acute MI. MI后3天，BNP-Tg小鼠中浸润梗死区的中性粒细胞数量显著增加。此外，MMP-9的基因表达和酶谱活性，而不是MMP-2，在BNP-Tg小鼠中显着高于非Tg小鼠。双重免疫组化显示，中性粒细胞的MMP-9的主要来源，虽然强力霉素，MMP抑制剂，没有影响中性粒细胞浸润的BNP-Tg mice. Conclusions，这些结果表明，血浆BNP升高有利于中性粒细胞浸润的梗死区MI后，增加MMP-9的活性，他们生产。提示BNP在急性心肌梗死后早期细胞外基质重塑和创伤愈合过程中起关键作用。
Background-Recent clinical trials have shown that systemic infusion of nesiritide, a recombinant human brain natriuretic peptide (BNP), improves hemodynamic parameters in acutely decompensated hearts. This suggests that BNP exerts a direct cardioprotective effect and might thus be a useful therapeutic agent with which to treat acute myocardial infarction (MI). In the present study, we used BNP-transgenic (BNP-Tg) mice with elevated plasma BNP to determine whether and how BNP contributes to left ventricular remodeling and healing after MI.Methods and Results-We examined the accumulation of neutrophils and the expression and activation of matrix metalloproteinase (MMP)-9 in the ventricles of male BNP-Tg mice and their nontransgenic (non-Tg) littermates during the early phase after acute MI. The numbers of neutrophils infiltrating the infarcted area were significantly increased in BNP-Tg mice 3 days after MI. In addition, both the gene expression and zymographic activity of MMP-9, but not MMP-2, were significantly higher in BNP-Tg than non-Tg mice. Double immunostaining revealed that neutrophils are the main source of the MMP-9, although doxycycline, an MMP inhibitor, had no effect on neutrophil infiltration of the infarcted area in BNP-Tg mice.Conclusions-These results demonstrate that elevated plasma BNP facilitates neutrophil infiltration of the infarcted area after MI and increases the activity of the MMP-9 they produce. This suggests that BNP plays a key role in the processes of extracellular matrix remodeling and wound-healing during the early phase after acute MI.