Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
J Cardiovasc Pharmacol Ther. 2009 Dec;14(4):339-46. doi: 10.1177/1074248409349620.
Increasing evidence suggests that the activation of p38 mitogen-activated protein kinase (p38MAPK) plays a role in cardiac remodeling. Targeting p38MAPK using drugs reported to interfere with its phosphorylation, namely statins and all-trans retinoic acid (atRA), might play a role in ameliorating this remodeling.
Cardiac remodeling was induced in male albino rats by chronic inhibition of nitric oxide (NO) synthesis by N-nitro L-arginine methyl ester (L-NAME). Daily oral administration of L-NAME for 4 weeks resulted in the elevation of mean arterial blood pressure (MABP) together with cardiac remodeling evidenced by an increase in left ventricular-body weight ratio together with an increase in cardiac hydroxyproline concentration and a decrease in left ventricular papillary muscle-developed tension. An elevation in cardiac phosphorylated p38MAPK concentration, tumor necrosis factor alpha concentration and in cardiac caspase 3 activity was also observed. Administration of either rosuvastatin or all-trans retinoic acid (atRA), starting 4 weeks after L-NAME administration, ameliorated remodeling and improved all studied parameters.
Targeting MAPK might represent a useful therapeutic avenue to ameliorate cardiac remodeling and support the notion that atRA and statins are potential candidates for the prevention and therapy of cardiac remodeling.
越来越多的证据表明，p38 丝裂原活化蛋白激酶（p38MAPK）的激活在心脏重构中发挥作用。使用据报道能干扰其磷酸化的药物（如他汀类药物和全反式视黄酸（atRA））来靶向 p38MAPK，可能在改善这种重构中发挥作用。
通过 N-硝基-L-精氨酸甲酯（L-NAME）慢性抑制一氧化氮（NO）合成，在雄性白化大鼠中诱导心脏重构。4 周的 L-NAME 口服给药导致平均动脉血压（MABP）升高，同时伴有左心室体重比增加，心肌羟脯氨酸浓度增加，左心室乳头肌发展张力降低，表明心脏重构。还观察到心脏磷酸化 p38MAPK 浓度、肿瘤坏死因子α浓度和心脏半胱天冬酶 3 活性升高。在 L-NAME 给药 4 周后开始给予瑞舒伐他汀或全反式视黄酸（atRA），可改善重构并改善所有研究参数。
靶向 MAPK 可能是改善心脏重构的一种有用的治疗途径，并支持这样一种观点，即 atRA 和他汀类药物是预防和治疗心脏重构的潜在候选药物。
