丁志威
阜外华中心血管病医院 心外三科室
INTRODUCTION:Atherosclerosis is characterized by endothelial cell dysfunction followed by lesion formation, arterial stenosis, potentially arterial occlusion, and severe outcomes. Novel treatments to slow or prevent the progression of the disease are of considerable clinical value. In the present study, we investigated the potential anti-atherosclerotic effects of the natural product juglanin in oscillatory shear stress (OSS) exposed endothelial cells.METHODS:Human aortic endothelial cells (HAECs) were exposed to OSS generated by a micro fluidal Teflon cone at 1 Hz frequency cycles (±5 dyn/cm2) in the presence or absence of 2.5 and 5 μM juglanin for 24 h. The expression levels of inflammatory factors and vascular adhesion molecules were evaluated using qRT-PCR, Western Blot, and ELISA. DHE assay was used to detect the production of ROS. The monocytic THP-1 cells were labeled with calcein-AM and incubated with HAECs for adhesion assay.RESULTS:Juglanin reduces OSS-induced oxidative stress by reducing the production of ROS through downregulation of NOX-2 and rescuing OSS-induced reduced expression of eNOS. Juglanin also inhibits the inflammatory response by suppressing OSS-induced expressions of IL-1β, MCP-1, and HMGB1. Using THP-1 monocytes, we show that juglanin reduces the attachment of monocytes to endothelial cells by inhibiting the expression of VCAM-1 and E-selectin. Moreover, Juglanin rescues OSS-reduced expression of atheroprotective transcriptional factor KLF2.CONCLUSIONS:Our findings indicate that juglanin protects against various atheroprone OSS-induced endothelial dysfunction. Juglanin has potential implication as a candidate for vascular intervention of atherosclerosis.
International immunopharmacology 2020
OBJECTIVE:To explore the predictive value of overall longitudinal strain for the development of cardiomyopathy without hypertrophic changes.METHODS:Sixty five patients with suspected hypertrophic cardiomyopathy (HCM) but without hypertrophic changes were selected. Genetic variant, overall longitudinal strain, left ventricular ejection fraction, end diastolic volume, end systolic volume, interventricular septal thickness, left ventricular diameter and end diastolic diameter were detected. The risk factors of HCM were analyzed.RESULTS:Forty four variants of 16 genes were identified, among which MYBPC3 13659G>A was the commonest (73.20%) and MYH7 13252C>T was the second (31.25%). MYBPC3 GG genotype, overall longitudinal strain and apical longitudinal strain were correlated with HCM (P<0.05).CONCLUSION:The increase of longitudinal strain is of great value in predicting the occurrence of HCM.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2020
The aim of this study is to study the effect of betulin (BE) on myocardial injury in diabetic mice. Insulin-related indexes and inflammation-related cytokines are detected by commercial kits. The mechanism of BE on diabetic myocardial injury was studied by modern molecular biology techniques. BE significantly improved glocose tolerance, reduced lipid accumulation and reduced the content of inflammatory cytokines in diabetic mice. Furthermore, BE regulated Siti1/NLRP3/NF-κB signaling pathway in db/db mice and H9C2 cells. Siti1 inhibitor (EX-57) counteracted those changes. BE significantly protected against diabetic cardiomyopathy, which was related to the regulation of Siti1/NLRP3/NF-κB pathway.
International immunopharmacology 2020
Acute myocardial infarction (AMI) is associated with high rates of morbidity and mortality. Atherosclerosis is among the leading causes of AMI. The rupture or erosion of atherosclerotic plaques can obstruct coronary arteries, thereby leading to an acute inflammatory reaction to ischemic injury and cardiomyocyte apoptosis. Dimethyl fumarate (DMF) is a fumaric acid diester which is used for the treatment of psoriasis and multiple sclerosis. DMF is most well-known for its modulatory actions on the Nrf2 and NF-κB cellular signaling pathways. In the present study, we employed an oxygen-glucose deprivation/reoxygenation (OGD/R) model of myocardial ischemia/reperfusion injury using H9c2 cardiomyocytes to assess the potential protective effects of DMF. We found that DMF significantly improved cell viability and reduced the expression of pro-inflammatory cytokines and chemokines, including IL-6, IL-8, and MCP-1. We further demonstrated an antioxidant effect of DMF via reduced production of ROS, which was mediated through NOX4 inhibition. Tissue factor and ICAM-1 play a major role in left ventricular remodeling. DMF inhibited the expression of TF and ICAM-1 induced by OGD/R, which we demonstrated to be mediated through the Egr-1 signaling pathway, as silencing of Egr-1 suppressed the expression of TF and ICAM-1. Together, these findings demonstrate a potential role for DMF in the treatment of myocardial infarction.
International immunopharmacology 2020
BACKGROUND:Atherosclerosis is a common reason for acute cardio-cerebral vascular diseases. The purpose of this study was to clarify the functional effects of Notoginsenoside R1 (NGR1) on atherosclerosis.METHODS:HUVECS were exposed to oxidized low-density lipoprotein (ox-LDL) in the current study. The proliferation ability of HUVECS was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT). Flow cytometry assays were performed to evaluate the apoptosis of HUVECS. Ox-LDL caused inflammatory response and oxidative stress were assessed by checking pro-inflammatory cytokines and intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). The regulatory roles of NGR1 in HUVECs were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The interaction relationship between miR-221-3p and X-inactive specific transcript (XIST) or TNF-receptor-associated factor 6 (TRAF6) was predicted by bioinformatics tools. Dual-luciferase reporter and RNA pull-down assays were used to confirm the interaction relationship.RESULTS:Currently, ox-LDL inhibited proliferation and induced apoptosis, inflammatory response, and oxidative stress in HUVECs, which were alleviated by treatment with NGR1. Importantly, the increase of XIST in ox-LDL-induced HUVECs was abolished by NGR1. In addition, the gain-of-functional experiment suggested that the upregulation of XIST neutralized the protection effects of NGR1 in HUVECs treated with ox-LDL. In addition, miR-221-3p was a target of XIST in HUVECs as confirmed by dual-luciferase reporter and RNA pull-down assays. Furthermore, miR-221-3p interacted with TRAF6, and NGR1 regulated proliferation, apoptosis, inflammatory response, and oxidative stress in HUVECs exposed to ox-LDL by regulation of the XIST/miR-221-3p/TRAF6 axis through Nuclear Factor Kappa B (NF-κB) pathway.CONCLUSION:NGR1 could exert regulatory functions in ox-LDL-induced HUVECS by regulation of XIST/miR-221-3p/TRAF6 axis, which provided valuable insights into the development of potential therapeutic strategy for atherosclerosis.
Cellular signalling 2020
