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Na Yang,1,2,* Yong-Bo Hou,2,3,* Tian-Hao Cui,2 Jun-Ma Yu,2 Shu-Fang He,4,5 Hai-Juan Zhu1 1Department of Anesthesiology, Maternal and Child Medical Center of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Anesthesiology, The Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei), Hefei, Anhui, People’s Republic of China; 3Department of Anesthesiology, Wannan Medical College, Wuhu, Anhui, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu-Fang He; Hai-Juan Zhu, Email sfhe@ahmu.edu.cn; 35880762@qq.comBackground: Ischemic preconditioning-induced serum exosomes (IPC-exo) protected rat heart against myocardial ischemia/reperfusion injury. However, whether IPC-exo regulate replacement fibrosis after myocardial infarction (MI) and the underlying mechanisms remain unclear. MicroRNAs (miRs) are important cargos of exosomes and play an essential role in cardioprotection. We aim to investigate whether IPC-exo regulate post-MI replacement fibrosis by transferring cardioprotective miRs and its action mechanism.Methods: Exosomes obtained from serum of adult rats in control (Con-exo) and IPC groups were identified and analyzed, subsequently intracardially injected into MI rats following ligation. Their miRs profiles were identified using high-throughput miR sequencing to identify target miRs for bioinformatics analysis. Luciferase reporter assays confirmed target genes of selected miRs. IPC-exo transfected with selected miRs antagomir or NC were intracardially administered to MI rats post-ligation. Cardiac function and degree of replacement fibrosis were detected 4 weeks post-MI.Results: IPC-exo exerted cardioprotective effects against excessive replacement fibrosis. MiR sequencing and RT-qPCR identified miR-133a-3p as most significantly different between IPC-exo and Con-exo. MiR-133a-3p directly targeted latent transforming growth factor beta binding protein 1 (LTBP1) and protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA). KEGG analysis showed that transforming growth factor-β (TGF-β) was one of the most enriched signaling pathways with miR-133a-3p. Comparing to injection of IPC-exo transfected with miR-133a-3p antagomir NC, injecting IPC-exo transfected with miR-133a-3p antagomir abolished protective effects of IPC-exo on declining excessive replacement fibrosis and cardiac function enhancement, while increasing the messenger RNA and protein expression of LTBP1, PPP2CA, and TGF-β 1in MI rats.Conclusion: IPC-exo inhibit excessive replacement fibrosis and improve cardiac function post-MI by transferring miR-133a-3p, the mechanism is associated with directly targeting LTBP1 and PPP2CA, and indirectly regulating TGF-β pathway in rats. Our finding provides potential therapeutic effect of IPC-induced exosomal miR-133a-3p for cardiac repair. Keywords: ischemic preconditioning, myocardial infarction, Exosomes, MicroRNAs, cardiac function, myocardial fibrosis

Purpose: To study whether serum triglyceride (TG) was associated with coronary heart disease (CHD) mortality.Methods: A cohort analytic study carried out in a machinery factory in Xi'an, China on 1696 subjects aged 35 years or above (1124 men and 572 women) examined in 1976 and followed up till 2000.Results: At baseline, the mean serum total cholesterol (TC) and triglyceride (TG) was 4.64 and 1.16 mmol/L in men, 4.62 and 1.10 mmol/L in women, respectively. Three hundred six (239 men, 67 women) had died within 37,781 person-years of follow-up, with 49 CHD deaths (36 male, 13 female). The relative risk (95% confidence interval) of CHD mortality per mmol/L increase in TG was 2.13 (1.46-3.17) after adjusting for age, marital status, occupation, education, systolic blood pressure and TC. Dose-response relationship between TG levels by tertiles and CHD risk was found. Stratified analyses showed TG was an independent predictor for CHD mortality in subjects with lower or higher TC.Conclusions: Chinese had lower levels of TC and TG than Western populations. This study provides new evidence that TG is an independent risk factor of CHD in subjects with lower or higher TC levels, and supports the lowering of cut-off value for elevated triglyceride. [ABSTRACT FROM AUTHOR]