Search

Angiogenesis contributes to plaque instability in atherosclerosis and further increases cardio-cerebrovascular risk. Circular RNAs (circRNAs) are promising biomarkers and potential therapeutic targets for atherosclerosis. Previous studies have demonstrated that tetramethylpyrazine (TMP) and paeoniflorin (PF) combination treatment (TMP-PF) inhibited oxidized low-density lipoprotein (ox-LDL)-induced angiogenesis in vitro. However, whether circRNAs regulate angiogenesis in atherosclerosis and whether TMP-PF can regulate angiogenesis-related target circRNAs in atherosclerosis are unknown. In this study, human RNA sequencing (RNA-seq) data were analysed to identify differentially expressed (DE) circRNAs in atherosclerosis and to obtain angiogenesis-associated circRNA-microRNA (miRNA)-messenger RNA (mRNA) networks. Target circRNA-related mechanisms in angiogenesis in atherosclerosis and the regulatory effects of TMP-PF on target circRNA signalling were studied in ox-LDL-induced human umbilical vein endothelial cells (HUVECs) by cell proliferation, migration, tube formation, and luciferase reporter assays, real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. A novel circRNA (circular stimulator of chondrogenesis 1, circSCRG1) was initially identified associated with angiogenesis in atherosclerosis, and circSCRG1 silencing up-regulated miR-1268b expression, increased nuclear receptor subfamily 4 group A member 1 (NR4A1) expression and then promoted ox-LDL-induced angiogenesis. TMP-PF (1 μmol/L TMP combined with 10 μmol/L PF) up-regulated circSCRG1 expression, mediated miR-1268b to suppress NR4A1 expression and then inhibited ox-LDL-induced angiogenesis. However, circSCRG1 silencing abolished the inhibitory effects of TMP-PF on ox-LDL-induced angiogenesis, which were rescued by the miR-1268b inhibitor. In conclusion, circSCRG1 might serve as a new target regulating angiogenesis in atherosclerosis via the circSCRG1/miR-1268b/NR4A1 axis and TMP-PF could regulate the circSCRG1/miR-1268b/NR4A1 axis to inhibit angiogenesis in atherosclerosis in vitro, indicating a novel angiogenesis signalling circSCRG1/miR-1268b/NR4A1 pathway in atherosclerosis and the regulatory effects of TMP-PF, which might provide a new pharmaceutical strategy to combat atherosclerotic plaque instability. [ABSTRACT FROM AUTHOR]

Summary: Aim: It is not clear whether treatment by vascular endothelial growth factor (VEGF) gene transfer can improve myocardial ischemia through a proangiogenesis mechanism and is effective against coronary artery disease (CAD). We aimed to perform a systematic review and meta‐analysis of randomized controlled trials (RCTs) that compared VEGF gene therapy and standard treatments in CAD. Methods: We systematically searched the PubMed, Embase, and Cochrane databases and relevant references for RCTs (published up to May 2018; no language restrictions) and performed meta‐analysis using both fixed and random effects models. Our primary outcome measures were mortality and serious cardiac events. The secondary outcome measures were follow‐up left ventricular ejection fraction (LVEF), change in LVEF (ΔLVEF), and angina outcomes. The registration number is CRD42017058430. Results: Of 524 identified studies, 14 were eligible and were included in our analysis. At a mean follow‐up of 6 months, VEGF gene therapy demonstrated a decreased risk of serious cardiac events (11.7% vs 21.2%, relative risk: 0.56; 95% confidence interval (CI): 0.37, 0.84; P = 0.005) and a slight improvement in follow‐up LVEF (weighted mean difference: 1.95; 95%CI: 1.28, 2.62). Furthermore, VEGF gene therapy using adenoviral vectors showed more potential benefit in terms of the risk of serious cardiac events, ΔLVEF, and Canadian Cardiovascular Society angina class. Nevertheless, mortality and angina frequency scores were not different. Conclusions: Vascular endothelial growth factor gene therapy appears to be safe and effective regarding serious cardiac events, with greater benefit when using adenoviral vectors. This meta‐analysis highlights the need for further exploration in these areas. [ABSTRACT FROM AUTHOR]

We previously reported a novel danshensu derivative (R)-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (ADTM) that exhibited promising cardiovascular protective activities, such as antioxidant and antiplatelet activities, as well as arterial relaxation. Particularly, ADTM treatment for 24 h exhibited anti-oxidative activity and effectively protected against acute myocardial infarction (MI) in a rat model. Here, we further investigated the pharmacological actions of 14 days of treatment with ADTM in alleviating and restoring the MI size by stimulating revascularization. The pro-angiogenesis activity of ADTM has been validated in multiple experimental models including MI mouse, zebrafish, human umbilical vein endothelial cells (HUVECs) and A7r5 vascular smooth muscle cells (VSMCs). In addition, the effect of ADTM on L-type Ca 2 + current ( I CaL ) was determined. We demonstrated that ADTM (12–24 mg/kg) treatment for 14 days significantly decreased myocardial infarct size, increased the blood vessel density compared to vehicle in the myocardial peri-infarct area, and ADTM (24 mg/kg) enhanced the serum VEGF level in MI mice ( P < 0.05). We also demonstrated that treatment with ADTM at 50–200 μM rescued chemical-induced blood vessel loss in zebrafish. Although ADTM did not directly promote the features of angiogenesis in HUVECs, ADTM significantly increased VEGF production in a dose-dependent manner in A7r5 cells ( P < 0.05). A patch clamp experiment demonstrated that ADTM (200 μM) inhibited I CaL at all depolarizing voltages, with > 50% inhibition at + 10 mV. Taken together, our results indicated that ADTM served as a Ca 2+ current blocker, promoted angiogenesis and reduced experimental myocardial infarct size in mice, probably through stimulation of VEGF production in VSMCs. [ABSTRACT FROM AUTHOR]

Puerarin, a bioactive natural C -glycoside isoflavonoid isolated from Pueraria lobata (Willd.) Ohwi, possesses many potential health benefits. However, the in vivo metabolic fates of puerarin have not been comprehensively clarified yet. In this study, an efficient strategy based on UHPLC-LTQ-Orbitrap mass spectrometer in both positive and negative ion modes was developed to profile and characterize puerarin metabolites in rat urine and plasma. Meanwhile, post-acquisition data-mining methods including high-resolution extracted ion chromatogram (HREIC) and multiple mass defect filtering (MMDF) were utilized to screen potential puerarin metabolites from HR-ESI–MS 1 stage. The mass fragmentation behaviors of five reference standards, including puerarin, daidzin, daidzein, genistin, and genistein, were comprehensively studied for construction of diagnostic product ions (DPIs), which could be employed to implement rapid identification of puerarin metabolites. Finally, a total of 66 metabolites (prototype compound included) were tentatively or positively identified based on standard substances, chromatographic retention times, accurate mass measurement, and corresponding Clog P values. Our results demonstrated that puerarin underwent multiple in vivo metabolic reactions including methylation, hydroxylation, dehydroxylation, hydrogenation, deglycosylation, glycosylation, sulfonation, glucuronidation, and their complicated reactions. In conclusion, the newly discovered puerarin metabolites significantly expanded the understanding on its pharmacological effects and built the foundation for further toxicity and safety studies. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of liraglutide in patients with Type 2 Diabetes Mellitus (T2DM) complicated with Coronary Artery Disease (CAD), we searched PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Wanfang Database and Chinese Biomedical Literature database (CBM) for relevant randomized controlled trials (RCTs) from inception to 7 October 2020. A total of 18 RCTs including 1557 patients with T2DM complicated with CAD were included. Meta-analysis revealed liraglutide reduced hemoglobin A1c (HbA1c) (WMD = −0.67; 95% CI[−0.94 to −0.39]; P < 0.00001), fasting plasma glucose (FPG) (WMD = −0.80; 95% CI[−1.06 to −0.54]; P < 0.00001) and 2 h plasma glucose (2hPG) (WMD = −1.64; 95% CI[−2.12 to −1.16]; P ＜0.00001); improved left ventricular ejection fraction(LVEF) (WMD = 4.79; 95% CI[4.08–5.51]; P < 0.00001), left ventricular end-diastolic diameter (LVEDD) (WMD = −5.70; 95% CI[−6.67 to −4.72]; P ＜0.00001), E/A (WMD = 0.13; 95% CI[0.11–0.14]; P < 0.00001) and left ventricular posterior wall thickness (LVPWT) (WMD = −1.86; 95% CI[−2.16 to −1.55]; P < 0.00001); reduced total cholesterol (TC) (WMD = −0.48; 95% CI[−0.56 to −0.39]; P < 0.00001), triglycerides (TG) (WMD = −0.42; 95% CI[−0.59 to −0.26]; P < 0.00001), low-density lipoprotein cholesterol (LDL-C) (WMD = −0.41; 95% CI[−0.55 to −0.26]; P < 0.00001), and increased high-density lipoprotein cholesterol (HDL-C) (WMD = −0.19; 95% CI[0.13–0.24]; P = 0.0005). As for safety assessment, liraglutide did not increase the incidence of hypoglycemia (OR = 0.75, 95% CI[0.32–1.77], P = 0.51) and gastrointestinal (OR = 1.15, 95% CI[0.72–1.85], P = 0.55) events. Consequently, liraglutide had favorable effects on blood glucose, cardiac function, lipid profile and an acceptable safety profile. [Display omitted] • Little is known about the cardioprotective effects of antidiabetic drugs. • Liraglutide significantly reduced blood glucose, improved lipid metabolism. • Liraglutide protected cardiac function in T2DM patients complicated with CAD. • Liraglutide prevented ventricular remodeling in T2DM patients complicated with CAD. • Liraglutide showed no increased risk in gastrointestinal and hypoglycemia events. [ABSTRACT FROM AUTHOR]

Aqueous Zn‐ion batteries are an attractive electrochemical energy storage solution for their budget and safe properties. However, dendrites and uncontrolled side reactions in anodes detract the cycle life and energy density of the batteries. Grain boundaries in metals are generally considered as the source of the above problems but we present a diverse result. This study introduces an ultra‐high proportion of grain boundaries on zinc electrodes through femtosecond laser bombardment to enhance stability of zinc metal/electrolyte interface. The ultra‐high proportion of grain boundaries promotes the homogenization of zinc growth potential, to achieve uniform nucleation and growth, thereby suppressing dendrite formation. Additionally, the abundant active sites mitigate the side reactions during the electrochemical process. Consequently, the 15 μm Fs−Zn||MnO2 pouch cell achieves an energy density of 249.4 Wh kg−1 and operates for over 60 cycles at a depth‐of‐discharge of 23 %. The recognition of the favorable influence exerted by UP‐GBs paves a new way for other metal batteries. [ABSTRACT FROM AUTHOR]

Inflammatory disorders result from abnormal immune response and their incidence has increased recently. Thus, there is an urgent need to discover new treatments for inflammatory disorders. In recent years, the natural products contained in Chinese herbs have attracted much attention worldwide owing to their anti-inflammatory effects. Paeoniflorin (PF) is a bioactive compound purified from the Chinese herb Paeonia lactiflora and reports have recently emerged suggesting the great potential of P. lactiflora as an agent to counter inflammatory disorders. The anti-inflammatory effects of PF have been revealed by in vitro studies and in vivo animal experiments of different inflammatory disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and asthma. This review systematically describes the recent progress of studies on the mechanism of PF and its therapeutic potential in inflammatory disorders. Image 1 [ABSTRACT FROM AUTHOR]

Atherosclerotic plaque angiogenesis is key factor in plaque instability and vulnerability, and low concentrations of oxidized low density lipoprotein (ox-LDL) promote the in vitro angiogenesis of endothelial cells and play an important role in plaque angiogenesis. Ligusticum chuanxiong Hort. and Radix Paeoniae Rubra herb pair in Chinese medicine obtains the optimum therapeutic efficacy in atherosclerosis, and their major active ingredients tetramethylpyrazine (TMP) and paeoniflorin (PF) are reported to alleviate atherosclerosis. The aim of this study was to investigate the effects of TMP and PF on ox-LDL-induced angiogenesis and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were incubated with ox-LDL and were then treated with TMP, PF, or a combination of TMP and PF. Cell proliferation, migration, tube formation, and the expression of angiogenesis-related proteins were measured. Synergism was evaluated using the combination index in cell proliferation. We found that TMP and PF attenuated the in vitro angiogenesis in ox-LDL-induced HUVECs. In addition, the combination of TMP and PF not only inhibited the ox-LDL-induced expression of CD31, vascular endothelial growth factor (VEGF), and VEGF receptor 2 (VEGFR2) but also decreased the ox-LDL-induced expression of Notch1, Jagged1, and Hes1. In summary, the combination of TMP and PF suppresses ox-LDL-induced angiogenesis in HUVECs by inhibiting both the VEGF/VEGFR2 and the Jagged1/Notch1 signaling pathways, which might contribute to the stability of plaques in atherosclerosis. [ABSTRACT FROM AUTHOR]

Tongxinluo capsule (TXLC) is a widely used traditional Chinese medicine for coronary heart disease (CHD). However, the efficacy and safety of different courses of TXLC for CHD after percutaneous coronary intervention (PCI) have not been systematically evaluated yet. The Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database were searched from the inception to 26 August 2021. A meta-analysis was performed using a fixed- or random-effects model. The risk of adverse cardiovascular events, mortality, or adverse effects was evaluated by risk ratio (RR) with 95% confidence interval (CI). Thirty-four studies involving 3652 patients were finally included. After the 6-month treatment, compared with conventional treatment alone, TXLC combined with conventional treatment achieved better efficacy in lowering the risk of angiographic restenosis (RR = 0.37, 95% CI = 0.28–0.48, p < 0.001), myocardial infarction (RR = 0.38, 95% CI = 0.25–0.60, p < 0.001), heart failure (RR = 0.32, 95% CI = 0.18–0.56, p < 0.001), angina (RR = 0.26, 95% CI = 0.17–0.38, p < 0.001), revascularization (RR = 0.20, 95% CI = 0.09–0.46, p < 0.001), all-cause mortality (RR = 0.24, 95% CI = 0.10–0.58, p = 0.001), and mortality due to any cardiovascular event (RR = 0.27, 95% CI = 0.09–0.80, p = 0.018). After the 12-month treatment, TXLC reduced the recurrence risk of angina (RR = 0.40, 95% CI = 0.20–0.80, p = 0.009). However, there was no difference in any outcomes after the 3-month treatment. Besides, no difference was found in the incidence of adverse effects after the 3-month and 6-month treatments (3 months: RR = 0.73, 95% CI = 0.35–1.56, p = 0.418; 6 months: RR = 1.71, 95% CI = 0.74–3.93, p = 0.209). The certainty of evidence ranged from very low to moderate due to the risk of bias, inconsistency, and imprecision. TXLC showed beneficial effects on reducing the adverse cardiovascular events without compromising safety for CHD patients after PCI on the 6-month course. However, due to the unavoidable risk of bias, more high-quality and long-term studies are still needed to further evaluate the efficacy and safety of TXLC in many countries, not only in China. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) and fatigue are two common diseases endangering human life and health that may interact and reinforce one another. Myocardial infarction survivors frequently experience fatigue, and acute myocardial infarction (AMI) is one of the most common cardiovascular diseases that cause fatigue-induced sudden death. Sheng Mai Yin (SMY), a Chinese medicine prescription, is traditionally used for the treatment of diabetes and cardiovascular disease, and has been demonstrated to reduce fatigue and safeguard cardiac function. This study aims to investigate the effects and underlying mechanisms of SMY in treating fatigue and AMI. The pharmacological mechanisms of SMY in treating fatigue and AMI were predicted by bioinformatics and network pharmacology methods. After administering SMY at high, medium and low doses, the swimming time to exhaustion, hemoglobin level, serological parameters and hypoxia tolerance time were detected in C57BL/6N mice, and the left ventricular ejection fractions (LVEF), left ventricular fractional shortening (LVFS), grasp strength, cardiac histopathology, serological parameters and the expression of PINK1 and Parkin proteins were examined in Wistar rats. 371 core targets for SMY and 282 disease targets for fatigue and AMI were obtained using bioinformatics and network pharmacology methods. Enrichment analysis of target genes revealed that SMY might interfere with fatigue and AMI through biological processes such as mitochondrial autophagy, apoptosis, and oxidative stress. For in vivo experiments, SMY showed significant anti-fatigue and hypoxia tolerance effects in mice; It also improved the cardiac function and grasp strength, decreased their cardiac index, myocardial injury and fibrosis degree, and induced serological parameters levels and the expression of PTEN-induced putative kinase 1 (PINK1) and Parkin proteins in myocardium, suggesting that SMY may exert cardioprotective effects in a joint rat model of fatigue and AMI by inhibiting excessive mitochondrial autophagy. This study revealed the anti-fatigue, anti-hypoxia and cardioprotective effects of SMY in a joint model of fatigue-AMI, and the pharmacological mechanism may be related to the inhibition of mitochondrial autophagy in cardiomyocytes through the PINK1/Parkin pathway. The discoveries may provide new ideas for the mechanism study of traditional Chinese medicine, especially complex prescriptions, in treating fatigue and AMI. [Display omitted] • Fatigue and acute myocardial infarction may be related to apoptotic process. • Sheng Mai Yin reduced fatigue, hypoxia and heart damage in mice and rats. • Sheng Mai Yin may suppress PINK1 and Parkin expression in the mitochondrial autophagy of myocardium. [ABSTRACT FROM AUTHOR]

Puerarin is an isoflavonoid isolated from the root of Pueraria lobata (Gegen in Chinese) that has been widely used to treat cardiovascular and cerebrovascular diseases in China. Here, we investigated the hypotensive effects and mechanisms of puerarin in spontaneously hypertensive rats. The qPCR array technique was used to determine the expression of hypertension-related genes. Then, the differentially expressed genes were analyzed using the STRING database. The systolic blood pressure and diastolic blood pressure of rats decreased after the administration of puerarin for nine weeks. Puerarin, but not losartan, also slowed the heart rate of rats. NO and cGMP levels were improved by puerarin. Eighteen differentially expressed hypertension-related genes were identified by comparing the model group with the control group and the high-dose puerarin group with the model group. NO and cGMP levels were increased by high-dose puerarin. High-dose puerarin increased the levels of the phosphorylated eNOS protein and decreased AT1 and Cav1 levels. Based on our results, eNOS was a key target in the mechanism by which puerarin reduced blood pressure, and puerarin represents a potential antihypertensive agent. [ABSTRACT FROM AUTHOR]