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.

Background: Exercise can induce physiological myocardial hypertrophy (PMH), and former athletes can live 5-6 years longer than nonathletic controls, suggesting a benefit after regression of PMH. We previously reported that regression of pathological myocardial hypertrophy has antihypertrophic effects. Accordingly, we hypothesized that antihypertrophic memory exists even after PMH has regressed, increasing myocardial resistance to subsequent pathological hypertrophic stress. Methods: C57BL/6 mice were submitted to 21 days of swimming training to develop PMH. After termination of exercise, PMH regressed within 1 week. PMH regression mice (exercise hypertrophic preconditioning group, EHP) and sedentary mice (control group) then underwent transverse aortic constriction (TAC) or a sham operation for 4 weeks. Cardiac remodeling and function were evaluated using echocardiography, invasive left ventricular hemodynamic measurement and histological analysis. LncRNA sequencing, chromatin immunoprecipitation assay (ChIP), and comprehensive identification of RNA-binding proteins by mass spectrometry (CHIRP-MS) and Western blot were used to investigate the role of Mhrt779 involved in the anti-hypertrophy effect induced by EHP. Results: At 1 and 4 weeks after TAC, the EHP group showed less increase in myocardial hypertrophy and lower expression of the Nppa and Myh7 genes than the sedentary group. At 4 weeks after TAC, EHP mice had less pulmonary congestion, smaller left ventricular dimensions and end-diastolic pressure, and a larger left ventricular ejection fraction and maximum pressure change rate than sedentary mice. Quantitative polymerase chain reaction (qPCR) revealed that the long noncoding myosin heavy chain associated RNA transcript Mhrt779 was one of the markedly upregulated long noncoding RNAs in the EHP group. Silencing of Mhrt779 attenuated the antihypertrophic effect of EHP in mice with TAC and in cultured cardiomyocytes treated with angiotensin II, and overexpression enhanced the antihypertrophic effect. By ChIP and qPCR, we found that EHP increased histone 3 trimethylation (H3K4me3 and H3K36me3) at the a4 promoter of Mhrt779 . CHIRP-MS and Western blot showed that Mhrt779 can bind Brg1 to inhibit the activation of Hdac2/Akt/GSK3β pathway induced by pressure overload. Conclusions: Myocardial hypertrophy preconditioning evoked by exercise increases resistance to pathological stress via an antihypertrophic effect mediated by a signal pathway of Mhrt779 /Brg1/Hdac2/p-Akt/p-GSK3β.

Background: An increasing number of studies have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors, initially used as antidiabetic agents, have cardiovascular (CV) benefits. However, few bibliometric analyses have examined this field systematically. Our study aimed to visualize the publications to determine the trends and hotspots in CV research on SGLT2 inhibitors. Methods: Publications on SGLT2 inhibitors in cardiovascular research were retrieved from the Web of Science Core Collection. Microsoft Excel 2019, VOSviewer, and CiteSpace V were used to analyze and plot the references. Results: On July 3, 2020, 1509 records of CV research on SGLT2 inhibitors published from 2013 to 2020 were retrieved. Nearly half were authored by American scholars, and most were published in Diabetes Obesity Metabolism, Cardiovascular Diabetology, and Diabetes Therapy. The USA was the leading driving force, with a strong academic reputation in this area. Inzucchi SE published the most related articles, while Neal B was cited the most frequently. All the top 10 co-cited references were in the leading co-cited journal, The New England Journal of Medicine. "Atherosclerotic cardiovascular event" was the leading research hotspot. The keywords "cardiac metabolism," "heart failure hospitalization," and "heart failure with preserved ejection fraction" appeared most recently as research frontiers. Conclusion: Most studies focused on clinical trial outcomes, such as cardiovascular death and heart failure (HF) hospitalization. The mechanisms of SGLT2 inhibitors, especially those related to cardiac metabolism, may soon become hotspots and should be closely monitored.