Abstract： Objective To investigate the effects of hepatocyte growth factor（HGF）gene transfected bone marrow mesenchymal stem cells （MSCs）transplantation in pigs with chronic ischemic heart disease. Methods MSCs were isolated from pig bone marrow by density gradient centrifugation and adherent cell culture, purified, and determined by cellsurface antigens（CD34, CD44, CD71, Ⅷ factor and desmin）. MSCs were transfected by adenovirus expressing hepatocyte growth factor（AdHGF）, and the influence of HGF on the biological characteristics of MSCs was tested. The pig model of chronic myocardial ischemia was established by placing Ameroid ring inside the left circumflex coronary artery via leftthoracotomy. A total of 40 pigs were randomly divided into 5 groups （n=8） and were injected 5×106/ml MSCs＋ 4×109 pfu 200 μl AdHGF （MSCs＋ AdHGF group）, 4×109 pfu 200 μl AdHGF （AdHGF group）, 5×106/ml MSCs 200 μl（MSCs group），4×109 pfu 200 μl AdNull （AdNull group）and 1 ml saline（control group） into the ischemic myocardiumrespectively. Echocardiogram, digital subtraction angiography （DSA） of coronary artery, single photon emission computed tomography（SPECT） myocardial perfusion imaging and cardiomyocyte apoptosis were examined after 4 weeks. Results Positive CD44 and CD71 and negative CD34, Ⅷ factorand desmin were detected in MSCs by flow cytometer. HGF had a b influence on stimulating the proliferation and differentiation of MSCs. Echocardiogram examination showed that left ventricular end-diastolic volume（LVEDV），left ventricular ejection fraction（LVEF），fractional shortening（FS）of MSCs＋ AdHGF group were significantly increased after treatment （P＜ 0.05）. DSA detection showed that ischemic neovascularization of MSCs＋ AdHGF group was significantly higher than those of AdHGF group and MSCs group （P＜ 0.05）. SPECT showed that the left ventricular myocardium of MSCs＋ AdHGF group appeared thickened,myocardial perfusion was significantly improved and the myocardial motion was significantly increased （P＜ 0.05）. Vascular density of MSCs＋ AdHGF group was significantly higher than those of AdHGF group and MSCs group by HE stain of myocardium ［（39.4±1.2）/ HPF vs. （36.5±1.4）/ HPF and（34.5±1.7）/ HPF，P＜ 0.05］. Cardiomyocyte apoptosis rate of MSCs＋ AdHGF group was significantly lower than those of AdHGF group and MSCs group by TUNEL stain （P＜ 0.05）. Conclusion Combination transplantation can promote the angiogenesis of chronic ischemic myocardium, inhibit cardiomyocyte apoptosis and improve heart function in pigs with chronic ischemic heart disease. The effect of HGF gene transfected MSCs transplantation is better than that of MSCs or HGF transplantation alone.
ObjectiveTo assess the burden of ischemic heart disease attributable to low physical activity and high body mass index among the population aged 60 years and above in China from 1990 to 2023, and to predict the changing trends of the corresponding burden from 2024 to 2038, so as to lay a theoretical foundation for formulating comprehensive prevention and control measures. MethodsWe utilized the estimated annual percentage change (EAPC) to analyze the trends in disability-adjusted life years (DALYs) and mortality burden of ischemic heart disease attributable to high body mass index and low physical activity among the elderly population in China, along with exploring sex and age-group differences in the related burden. Furthermore, the Bayesian age-period-cohort model was employed for predictive analysis. ResultsEAPC analyses indicated that the age-standardized mortality rate (ASMR) and age-standardized DALYs rate of ischemic heart disease attributable to low physical activity and high body mass index among the Chinese elderly population increased from 1990 to 2023. Regarding sex differences, the burden caused by low physical activity was more severe in elderly females, while the burden attributed to high body mass index was heavier in elderly males. During the projection period, only the ASMR due to low physical activity in elderly males was expected to present a decreasing trend, while all other types of burdens were forecast to rise. ConclusionThe burden of ischemic heart disease attributable to the above two modifiable risk factors continues to escalate among the elderly population in China. Therefore, it is necessary to implement precision prevention and control strategies ranging from the macro level to the individual level, with full consideration of sex heterogeneity, so as to alleviate the disease burden effectively.