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Systemic and pulmonary arterial hypertension (PAH) can induce left and right ventricular hypertrophy, respectively, but common therapeutic targets for both left and right hypertrophy are limited. In this study, we attempt to explore potential common therapeutic targets and screen out potential target drugs for further study. Cardiac mRNA expression profiles in mice with transverse aortic constriction (TAC) and pulmonary arterial constriction (PAC) are obtained from online databases. After bioinformatics analyses, we generate TAC and PAC mouse models to validate the phenotypes of cardiac remodelling as well as the identified hub genes. Bioinformatics analyses show that there are 214 independent differentially expressed genes (DEGs) in GSE136308 (TAC related) and 2607 independent DEGs in GSE30922 (PAC related), while 547 shared DEGs are associated with the function of the extracellular matrix (ECM) or involved in the PI3K-Akt signaling pathway, cytokine-cytokine receptor interactions, and ECM-receptor interactions. We identifyd Fn1, Il6, Col1a1, Igf1, Col1a2, Timp1, Col3a1, Cd44, Ctgf and Postn as hub genes of the shared DEGs, and most of them are associated with myocardial fibrosis. Those hub genes and phenotypes of cardiac remodelling are validated in our TAC and PAC mouse models. Furthermore, we identify dehydroisoandrosterone (DHEA), iloprost and 4,5-dianilinophthalimide (DAPH) as potential therapeutic drugs targeting both left and right ventricular hypertrophy and validate the effect of DHEA. These findings suggest that DHEA could be an effective drug for pressure overload-induced left or right ventricular hypertrophy by regulating the shared hub differentially expressed genes associated with fibrosis.

Context Both physical activity (PA) and sedentary behavior (SB) exert an important impact on type 2 diabetes, but it remains unclear regarding how the maximum impact on improving mortality by an optimized proportion of the two lifestyles can be achieved. Objective To explore the impacts of PA/SB combinations on mortality in patients with diabetes. Methods Patients with type 2 diabetes samplings were collected from the National Health and Nutrition Examination Survey dataset. Their lifestyles were categorized into 8 groups based on combinations of the PA and SB levels. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. Results During the follow-up period, 1148 deaths (18.94%) were recorded. High SB (sedentary time ≥6 hours/day) was significantly associated with higher all-cause mortality [hazards ratio (HR) 1.65]. In participants with low SB (<6 hours/day), low PA was associated with lower all-cause mortality (HR 0.43), while a further increase of PA level did not show further reductions in either all-cause or cardiovascular mortality. In contrast, in participants with high SB, all levels of PA were associated with lower all-cause mortality (P <.05), but only moderate PA was associated with lower cardiovascular mortality (HR 0.30). Conclusion In patients with type 2 diabetes, different combinations of various levels of PA and SB are associated with different degrees of risk for all-cause or cardiovascular mortality. [ABSTRACT FROM AUTHOR]