AT1-receptor blockade: Protective effects of irbesartan in cardiomyocytes under hypoxic stress.
AT1-receptor blockade: Protective effects of irbesartan in cardiomyocytes under hypoxic stress.
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DOI：
10.1371/journal.pone.0202297
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Rinaldi B
中科院分区：
文献类型：
--
作者：
Boccellino M;Di Domenico M;Donniacuo M;Bitti G;Gritti G;Ambrosio P;Quagliuolo L;Rinaldi B
缺氧通过激活炎症和氧化过程诱导心肌损伤。肾素血管紧张素系统（RAS）在心血管疾病发病机制中的关键作用已在临床试验和实践中得到牢固确立;事实上，许多实验和临床数据都强调了其抑制具有心脏保护作用。活化的RAS还刺激炎症，直接诱导促炎和氧化基因表达。本研究旨在研究厄贝沙坦预处理（10和100 μM）对HL-1心肌细胞缺氧24 h诱导的损伤的保护作用;特别是，我们分析了利钠肽（BNP）的表达，BNP是一种能够调节心脏损伤炎症反应的生物标志物，以及一些参与氧化应激和炎症的标志物。我们的结果表明，与缺氧细胞相比，100 μM厄贝沙坦预处理可显着增加SOD活性和过氧化氢酶表达，分别增加15%和25%（P<0.05）。另一方面，能使过氧亚硝基阴离子的释放和iNOS蛋白表达分别减少20%和50%（P<0.05）。此外，厄贝沙坦发挥抗炎活性，降低Toll样受体（TLR）-2和-4 mRNA表达、TNF-α表达和活性（20%），并增加细胞因子IL-17的表达（40%）（P<0.05 vs缺氧）。我们的研究结果还表明，脑缺血诱导的BNP显着降低，并在一个浓度依赖性的方式厄贝沙坦。我们的研究结果表明，AT 1受体拮抗剂厄贝沙坦在体外缺氧条件下发挥保护作用，减少氧化应激和炎症。
Hypoxia induces myocardial injury through the activation of inflammatory and oxidative processes. The pivotal role of the renin angiotensin system (RAS) in the pathogenesis of cardiovascular diseases has been firmly established in clinical trials and practice; in fact many experimental and clinical data have highlighted that its inhibition has a cardioprotective role. Activated RAS also stimulates inflammation directly inducing proinflammatory and oxidative gene expression. This study aimed to investigate the protective role of a pre-treatment (10 and 100 μM) with irbesartan on injury induced by 24 h of hypoxia in HL-1 cardiomyocytes; in particular, we have analyzed the natriuretic peptide (BNP) expression, a biomarker able to modulate inflammatory reaction to cardiac injury and some markers involved in oxidative stress and inflammation. Our results demonstrated that a pre-treatment with 100 μM irbesartan significantly increased SOD activity and catalase expression of 15 and 25%, respectively, compared to hypoxic cells (P<0.05). On the other hand, it was able to reduce the release of peroxynitrite and iNOS protein expression of 20 and 50% respectively (P<0.05). In addition irbesartan exerts an anti-inflammatory activity reducing Toll-like receptors (TLRs)-2 and -4 mRNA expression, TNF-alpha expression and activity (20%) and increasing the expression of the cytokine IL-17 (40%) (P<0.05 vs hypoxia). Our findings also showed that BNP induced by ischemia was significantly and in a concentration-dependent manner reduced by irbesartan. The findings of our study demonstrated that the AT1 receptor antagonist irbesartan exerts a protective role in an in vitro hypoxic condition reducing oxidative stress and inflammation.
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影响因子：
5.3
作者：
Liu, Zhendong;Zhao, Yingxin;Qi, Zaiwen
通讯作者：
Qi, Zaiwen
影响因子：
--
作者：
Min X;Lu M;Tu S;Wang X;Zhou C;Wang S;Pang S;Qian J;Ge Y;Guo Y;Xu D;Cao K
通讯作者：
Cao K
右美托咪定通过抑制 TLR4-MyD88-NF-kappa B 信号传导保护心肌细胞免受缺氧/复氧损伤
影响因子：
--
作者：
Gao JM;Meng XW;Zhang J;Chen WR;Xia F;Peng K;Ji FH
通讯作者：
Ji FH
影响因子：
2.4
作者：
D'Angelo, Stefania;La Porta, Raffaele;Boccellino, Mariarosaria
通讯作者：
Boccellino, Mariarosaria
影响因子：
24
作者：
Hirohata, Atsushi;Yamamoto, Keizo;Ohe, Tohru
通讯作者：
Ohe, Tohru