Chemerin-9-induced contraction was enhanced through the upregulation of smooth muscle chemokine-like receptor 1 in isolated pulmonary artery of pulmonary arterial hypertensive rats
Chemerin-9-induced contraction was enhanced through the upregulation of smooth muscle chemokine-like receptor 1 in isolated pulmonary artery of pulmonary arterial hypertensive rats
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DOI：
10.1007/s00424-019-02345-5
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发表时间：
2020-03-01
影响因子：
4.5
通讯作者：
Yamawaki, Hideyuki
中科院分区：
文献类型：
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作者：
Omori, Ayaho;Goshima, Makoto;Yamawaki, Hideyuki
Chmerin是一种具有心血管作用的脂肪细胞因子。趋化素样受体1(CMKLR1)和趋化因子(CC基序)受体2(CCRL2)是趋化素样受体。Chmerin-9是一种活性片段，通过平滑肌CMKLR1在分离的血管中引起收缩。肺动脉高压(PAH)是一种致命的疾病，最终导致右心衰竭。为了验证趋化蛋白影响肺动脉(PA)阻力的假说，我们研究了趋化蛋白-9对PAH大鼠分离的PA收缩功能的影响。给Wistar大鼠注射野百合碱(MCT)2周，造成PAH大鼠(MCT大鼠)。对照组(CONT)大鼠注射生理盐水。采用等长收缩实验方法，观察Chmerin-9对左肺离体肺内动脉收缩的影响。免疫印迹法检测左肺组织中CMKLR1和CCRL2的蛋白表达。免疫组织化学方法检测CMKLR1在左肺IPA的定位。与CONT大鼠相比，MCT大鼠IPA对Chmerin-9的收缩作用明显增强。与CONT大鼠相比，MCT大鼠左肺CMKLR1蛋白表达显著升高，诱骗受体CCRL2蛋白表达显著降低。CMKLR1主要定位于CONT大鼠IPA的内皮细胞。MCT组大鼠IPA内皮细胞CMKLR1表达显著降低，而血管内皮细胞CMKLR1表达显著升高。本研究首次证明趋化蛋白-9对MCT大鼠IPA收缩的增强作用至少部分是由平滑肌中CMKLR1的增加引起的。
Chemerin is an adipocytokine having cardiovascular effects. Chemokine-like receptor 1 (CMKLR1) and chemokine (CC motif) receptor-like 2 (CCRL2) are chemerin receptors. Chemerin-9, an active fragment, causes contraction via smooth muscle CMKLR1 in isolated blood vessels. Pulmonary arterial hypertension (PAH) is a fatal disease resulting ultimately in right heart failure. To test the hypothesis that chemerin affects pulmonary artery (PA) resistance, we examined the effects of chemerin-9 on contractility of isolated PA from PAH rats. Wistar rats were injected with monocrotaline (MCT) for 2 weeks to make PAH rats (MCT rats). Control (Cont) rats received a saline injection. Chemerin-9-induced contraction of isolated intrapulmonary artery (IPA) from left lung was isometrically measured. Protein expression of CMKLR1 and CCRL2 in isolated left lung was determined by Western blotting. Localization of CMKLR1 in IPA of left lung was examined immunohistochemically. Chemerin-9-induced contraction was significantly enhanced in IPA from MCT compared with Cont rats. Protein expression of CMKLR1 was significantly elevated in isolated left lung from MCT compared with Cont rats, while protein expression of CCRL2, a decoy receptor, was significantly decreased. CMKLR1 was localized mainly in endothelium of IPA in Cont rats. The CMKLR1 expression was significantly decreased in endothelium of IPA in MCT rats, while it was significantly elevated in smooth muscle. The present study for the first time demonstrated that the enhanced chemerin-9-induced contraction of isolated IPA from MCT rats was at least partly caused by the increase of CMKLR1 in smooth muscle.