ABSTRACT
Background: Rheumatic heart disease (RHD) remains the leading cause of preventable death and disability in children and young adults, killing an estimated 320,000 individuals worldwide yearly. Materials and methods: We utilized the Bayesian age-period cohort (BAPC) model to project the change in disease burden from 2020 to 2030 using the data from the Global Burden of Disease (GBD) Study 2019. Then we described the projected epidemiological characteristics of RHD by region, sex, and age. Results: The global age-standardized prevalence rate (ASPR) and age-standardized incidence rate (ASIR) of RHD increased from 1990 to 2019, and ASPR will increase to 559.88 per 100,000 population by 2030. The global age-standardized mortality rate (ASMR) of RHD will continue declining, while the projected death cases will increase. Furthermore, ASPR and cases of RHD-associated HF will continue rising, and there will be 2,922,840 heart failure (HF) cases in 2030 globally. Female subjects will still be the dominant population compared to male subjects, and the ASPR of RHD and the ASPR of RHD-associated HF in female subjects will continue to increase from 2020 to 2030. Young people will have the highest ASPR of RHD among all age groups globally, while the elderly will bear a greater death and HF burden. Conclusion: In the following decade, the RHD burden will remain severe. There are large variations in the trend of RHD burden by region, sex, and age. Targeted and effective strategies are needed for the management of RHD, particularly in female subjects and young people in developing regions.
ABSTRACT
D-4F, an apolipoprotein A-I (apoA-I) mimetic peptide, possesses distinctly anti-atherogenic effects. However, the biological functions and mechanisms of D-4F on the hyperplasia of vascular smooth muscle cells (VSMCs) remain unclear. This study aimed to determine its roles in the proliferation and migration of VSMCs. In vitro, D-4F inhibited VSMC proliferation and migration induced by ox-LDL in a dose-dependent manner. D-4F up-regulated heme oxygenase-1 (HO-1) expression in VSMCs, and the PI3K/Akt/AMP-activated protein kinase (AMPK) pathway was involved in these processes. HO-1 down-regulation with siRNA or inhibition with zinc protoporphyrin (Znpp) impaired the protective effects of D-4F on the oxidative stress and the proliferation and migration of VSMCs. Moreover, down-regulation of ATP-binding cassette transporter A1 (ABCA1) abolished the activation of Akt and AMPK, the up-regulation of HO-1 and the anti-oxidative effects of D-4F. In vivo, D-4F restrained neointimal formation and oxidative stress of carotid arteries in balloon-injured Sprague Dawley rats. And inhibition of HO-1 with Znpp decreased the inhibitory effects of D-4F on neointimal formation and ROS production in arteries. In conclusion, D-4F inhibited VSMC proliferation and migration in vitro and neointimal formation in vivo through HO-1 up-regulation, which provided a novel prophylactic and therapeutic strategy for anti-restenosis of arteries.
