AIMS Proton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms. METHODS AND RESULTS Adult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3β, and active β-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active β-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy. CONCLUSION Lansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3β/β-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.

中文翻译：

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兰索拉唑通过阻断β-catenin的活化，减轻了压力负荷引起的心脏肥大和心力衰竭。

AIMS质子泵抑制剂（PPI）广泛用于接受经皮冠状动脉介入治疗以预防胃出血的患者，但是PPI是否对心脏有益尚有争议。在这里，我们研究了兰索拉唑对心脏肥大和心力衰竭的影响，以及潜在的机制。方法和结果成年雄性C57小鼠接受主动脉缩窄（TAC）或假手术，然后用lansoprazole或溶媒治疗5周。另外，在存在或不存在兰索拉唑的情况下，将培养的新生大鼠心室心肌细胞和成纤维细胞暴露于血管紧张素II。在TAC后5周，兰索拉唑治疗的小鼠的心重/体重比低于未治疗的小鼠，肺重/体重比，兰索拉唑治疗的小鼠左心室（LV）缩短分数和LV压力的最大和最小变化率较高，而心脏纤维化较少。在培养的心肌细胞中，兰索拉唑抑制血管紧张素II诱导的蛋白质合成和肥大，并抑制成纤维细胞的增殖。兰索拉唑降低了TAC小鼠和血管紧张素II刺激的心肌细胞的磷酸化Akt，磷酸化糖原合酶激酶3β和活性β-连环蛋白的心肌水平。活性β-连环蛋白过表达或H + / K + -ATPaseα-亚基敲低后，兰索拉唑仍显着减轻心肌肥大。结论兰索拉唑通过抑制Akt /GSK3β/β-catenin途径的激活来抑制心脏重塑，而不受H + / K + -ATPase的抑制作用，