The novel peptide athycaltide-1 attenuates Ang II-induced pathological myocardial hypertrophy by reducing ROS and inhibiting the activation of CaMKII and ERK1/2.

Pathological myocardial hypertrophy initially develops as an adaptive response to cardiac stress, which can be induced by many diseases. It is accompanied by adverse cardiovascular events, including heart failure, arrhythmias, and death. The purpose of this research was to explore the molecular mechanism of a novel peptide Athycaltide-1 (ATH-1) in the treatment of Ang II-induced pathological myocardial hypertrophy. In this study, the mRNA of Control group, Ang II group, ATH-1 group and Losartan group mice were sequenced by high-throughput sequencing technology. The results showed that the differentially expressed genes (DEGs) were significantly enriched in cell response to oxidative stress, regulation of reactive oxygen species metabolism and calmodulin binding. Then, the oxidation level of mouse hearts and H9c2 cardiomyocytes in each group and the expression of key proteins of CaMKII/HDAC/MEF2C and ERK1/2 signaling pathways were detected to preliminarily verify the positive effect of ATH-1. At the same time, the effect of ATH-1 was further determined by adding reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) and CaMKII inhibitor AIP in vitro. The results showed that ATH-1 could significantly reduce the level of oxidative stress in hypertrophic cardiomyocytes and inhibiting the activation of CaMKII and ERK1/2.

Analysis of Therapeutic Targets of A Novel Peptide Athycaltide-1 in the Treatment of Isoproterenol-Induced Pathological Myocardial Hypertrophy.

Myocardial hypertrophy is a pathological feature of many heart diseases. This is a complex process involving all types of cells in the heart and interactions with circulating cells. This study is aimed at identifying the differentially expressed proteins (DEPs) in myocardial hypertrophy rats induced by isoprenaline (ISO) and treated with novel peptide Athycaltide-1 (ATH-1) and exploring the mechanism of its improvement. ITRAQ was performed to compare the three different heart states in control group, ISO group, and ATH-1 group. Pairwise comparison showed that there were 121 DEPs in ISO/control (96 upregulated and 25 downregulated), 47 DEPs in ATH-1/ISO (27 upregulated and 20 downregulated), and 116 DEPs in ATH-1/control (77 upregulated and 39 downregulated). Protein network analysis was then performed using the STRING software. Functional analysis revealed that Hspa1 protein, oxidative stress, and MAPK signaling pathway were significantly involved in the occurrence and development of myocardial hypertrophy, which was further validated by vivo model. It is proved that ATH-1 can reduce the expression of Hspa1 protein and the level of oxidative stress in hypertrophic myocardium and further inhibit the phosphorylation of p38 MAPK, JNK, and ERK1/2.

Associations of shift work and night work with risk of all-cause, cardiovascular and cancer mortality: a meta-analysis of cohort studies.

BACKGROUND: Epidemiological studies on the relationship of shift work or night work with risk of total and cause-specific mortality have given conflicting results. We aimed at conducting a meta-analysis to summarize the evidence from cohort studies. METHODS: Embase, PubMed, Web of Science and Scopus databases were searched for eligible studies up to Mar 2021. Cohort studies evaluating the associations of shift work or night work with risk of all-cause, cardiovascular or cancer mortality were reviewed. Study-specific risk estimates were pooled by fixed-effect models when the heterogeneity was not detected; otherwise, random-effect models were employed. RESULTS: We identified seventeen eligible articles (sixteen cohorts). A total of 958,674 cohort participants were included, with 38,413 total deaths, 24,713 cardiovascular deaths and 10,219 cancer deaths during follow-up. According to the Newcastle-Ottawa Scale, fifteen studies were considered as relatively high quality with low risk of bias. Compared with regular daytime workers, the pooled relative risks for all-cause, cardiovascular and cancer mortality were 1.02 (95% CI: 0.99, 1.06), 1.18 (95% CI: 0.94, 1.47) and 1.05 (95% CI: 0.83, 1.34) for those ever exposing to shift work, respectively. Compared with daytime workers or those never exposing to night work, the pooled relative risks for all-cause, cardiovascular and cancer mortality were 1.06 (95% CI: 1.03, 1.08), 1.15 (95% CI: 1.03, 1.29) and 1.04 (95% CI: 1.00, 1.08) for those ever exposing to night work, respectively. Moderate to high level of heterogeneity across the studies was detected. Publication bias was not detected. CONCLUSION: Night work may be associated with higher risk of all-cause, cardiovascular and cancer mortality, suggesting that night workers compared with daytime workers may be at higher risk of death, especially due to cardiovascular disease.

Combination therapy analysis of ezetimibe and statins in Chinese patients with acute coronary syndrome and type 2 diabetes.

BACKGROUND: Dyslipidemia management situation in Chinese patients with high risk and very high risk has been demonstrated very low, despite the wide use of statins. The effects and safety of the combined treatment of ezetimibe (EZ) and statins in Chinese patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (T2DM) remain unknown. METHODS: Chinese Patients with ACS and T2DM were divided into the statins group (n=40) and the combination group of EZ and statins (n=44). In order to evaluate the clinical effects on lipids-lowering, systemic inflammation response and clinical safety, the follow-up of all patients was carried out at day 7th and 30th after treatment. RESULTS: The level of low-density lipoprotein cholesterol (LDL-C) in combination group and statins group was 1.87±0.42 and 2.18±0.58 mmol/L at day 7th, 1.51±0.29 and 1.94±0.49 mmol/L at day 30th, respectively. The control rates of LDL-C level in the combination group and the statins group were 77% and 45% at day 30(th), respectively. There was no significant improvement on high-density lipoprotein cholesterol (HDL-C) level during follow-up. The triglyceride (TG) levels were significantly reduced in both groups, while no obvious difference was observed between two groups. No significant difference on serum high-sensitivity C-reactive protein (hs-CRP) level between two groups was observed. Moreover, we did not observe any significant correlation between serum lipids levels and serum hs-CRP level during follow-up. The liver dysfunction and muscle related side effects (MRSE), creatine kinase (CK) and myopathy were not observed in both groups. CONCLUSION: Our study demonstrated that it is feasible to initiate combination therapy during acute phase for Chinese patients with ACS and T2DM, which can bring more significant effect on LDL-C-lowering and improve the control rate of LDL-C level with good safety.