ABSTRACT
@#Dyslipidemia is a causal risk factor of atherosclerotic cardiovascular disease(ASCVD),and lipid-lowering therapies play a major role in preventing and managing ASCVD. Proprotein convertase subtilisin/kexin type 9(PCSK9)promotes atherosclerosis by increasing low-density lipoprotein cholesterol(LDL-C)and inflammatory response,while PCSK9 inhibitors can target to reduce PCSK9 levels and have high lipid lowering efficiency. Especially on the basis of statin or ezetimibe treatment,it can also bring more clinical benefits. With the in-depth study,PCSK9 inhibitor has become the research focus in recent years. This paper reviewed the development progress of PCSK9 inhibitors,in order to provide references for the clinical application of this class of drugs.
ABSTRACT
Objective:To analyze active components， its targets and signaling pathways of Shenlian formula based on network pharmacology， and explore the molecular mechanism of Shenlian formula in the treatment of atherosclerotic cardiovascular disease （ASCVD）， in order to provide a basis for the rational interpretation of the prescription compatibility of Shenlian formula. Method:Major chemical compounds of the formula were obtained by SymMap and Systematic pharmacology database and analysis platform of Traditional Chinese Medicine （TCMSP）， its target proteins were obtained by SymMap and ETCM Databases， and the pathogenic genes responsible for of ASCVD were obtained by DisGeNET and GEO Datebases. Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Shenlian Formula for ASCVD. Proteins-proteins interactions （PPI） network was built through the String Datebase. The Cytoscape 3.6.0 was used to explore the key compounds and targets of Shenlian formula on ASCVD. Then gene ontology （GO） enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway were analyzed to screen out the key targets of Shenlian Formula. Rat I/R model was adopted as representative disease model of ASCVD for experimental verification. Result:There were 59 candidate compounds， 67 predicted targets and 29 key targets of Shenlian formula on ASCVD. Key targets mainly included cyclooxygenase 2 （PTGS2）， estrogen receptor 1 （ESR1） and TP53. GO analysis showed that the biological functions of potential genes of Shenlian formula in treatment of ASCVD were mainly related to apoptotic， nitric oxide biosynthetic process， response to estradiol， angiogenesis， inflammatory response and oxidative stress and acute-phase response. KEGG pathway enrichment results showed that the pathways of potential genes of Shenlian formula in treatment of ASCVD mainly involved TNF signaling pathway， phosphatidylinositol-3 kinase （PI3K）/ protein kinase B （Akt） signaling pathway， hypoxia induction factor-1 （HIF-1） signaling pathway and apoptosis. Among them， the regulatory effect of Shenlian formula on apoptosis may act on not only TP53， but also different signaling pathways of apoptosis respectively， thus playing a synergistic effect. <italic>In vivo</italic> experimentation confirmed that Shenlian formula could significantly reduce the myocardial infarction area， improve the myocardial histopathological changes， and especially reduce myocardial mitochondrial injury. Further analysis showed that Shenlian formula can significantly inhibit the expressions of activated proteins in mitochondrial apoptosis pathway. Conclusion:Anti-atherosclerosis traditional Chinese medicine Shenlian formula could effectively intervene ASCVD， and its effect on mitochondrial apoptosis of myocardial cells is one of its mechanisms in protecting myocardial ischemia-reperfusion injury.
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【Objective】 To investigate the level of atherosclerotic cardiovascular disease (ASCVD) related indexes in plasma donors from longevity area, and explore its influencing factors. 【Methods】 1 027 plasma donors from longevity hotspot (Bama, Guangxi province) and 1 816 donors from non-longevity region (Shimen, Hunan province) who donated plasma during June to November 2018 were randomly selected. Triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), and fructosamine (FUN) of the two groups were measured and statistically analyzed. 【Results】 Compared with the non-longevity region group, the TG, TC and FUN levels of longevity hotspot group were lower (1.41±0.96 vs 2.31±1.28, 3.89±0.92 vs 4.04±0.82, 176.65±26.60 vs 200.33±34.19; all P<0.05), but HDLC, LDLC, Apo-A1 and Apo-B levels were higher (1.11±0.32 vs 0.96±0.25, 2.53±0.70 vs 2.29±0.56, 1.56±0.28 vs 1.23±0.18, 0.80±0.27 vs 0.72±0.19; all P<0.05). The yield (%) of high TG(12.0 vs 40.01) and FUN(0.58 vs 2.48), low HDLC(24.63 vs 43.90) and Apo-A1(1.66 vs 22.56) were lower in longevity area than those in non-longevity region (all P<0.05), but high LDLC(2.73 vs 0.28) and Apo-B(4.09 vs 0.22) yield(%) were higher in longevity area group ( P<0.05). The levels of TC, HDLC, LDLC, Apo-A1 and Apo-B were significantly different by ages (all P < 0.01), presenting positively correlated with age, significantly by gender and nationality, and slightly by blood type. 【Conclusion】 The ASCVD indexes of plasma donors from Bama were different from those from Shimen. Age, nationality, gender and blood type of donors from Bama all had a certain influence on these indexes levels.
ABSTRACT
Statins are important drugs for the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). The role and status of statins in ASCVD secondary prevention have been established, but the application of statins in ASCVD primary prevention in the elderly is controversial, especially in the elderly aged 75 years and older. The evidence for primary prevention with statins is not adequate. It should be cautious to initiate statins for primary prevention, because of the frailty, multicomobidity, polypharmacy and the limited life expectancy of the elderly may increase the risk of statins adverse reactions. The recent clinical studies and guidelines of statin primary prevention in the elderly population especially in aged 75 years and older have been reviewed in the paper. Making decisions based on fully evaluating the patients' ratio of benefits and risk with patients and implement statin individualized treatment strategies are emphasized.
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Millones de personas, sin indicación médica, toman aspirina para la prevención primaria de la enfermedad ateroesclerótica cardiovascular. La Sociedad Europea de Cardiología no la recomienda para prevención primaria de esta entidad y las Guías del ACC/ AHA sobre Prevención Primaria de la Enfermedad Ateroesclerótica Cardiovascular la recomiendan solo en personas con riesgo cardiovascular aumentado. El beneficio de la aspirina en pacientes con enfermedad cardiovascular establecida sobrepasa el riesgo de sangrado. Ese beneficio se debe al efecto antiinflamatorio y anti-plaquetario, que reduce el riesgo de aterotrombosis, pero con riesgo de sangrado particularmente en individuos susceptibles de sangrar. El papel de esta medicación en individuos sin enfermedad cardiovascular establecida es controversial en especial si tienen riesgo de sangrado. En esta comunicación se discuten las En las Guías del ACC/AHA, el estudio ASCEND en diabéticos, el ASPREE en ancianos sanos y el ARRIVE en pacientes con moderado a alto riesgo y otros para que sirva de alarma a los médicos generales y especialistas, a fin de que indaguen sobre el uso de aspirina en sus pacientes, y al mismo tiempo discutan sobre el balance entre el daño y los beneficios, particularmente en los pacientes ancianos y en aquellos con riesgo de sangrado. Se sugiere realizar un estudio para obtener la evidencia del número de personas que ingieren aspirina automedicada, realizar su seguimiento, y evolución una vez conocidas ampliamente e implementadas las presentes recomendaciones(AU)
Millions of people, without medical indication, take aspirin for the primary prevention of cardiovascular atherosclerotic disease. The European Society of Cardiology does not recommend it for primary prevention, and the ACC/AHA Guidelines on Primary Prevention of Cardiovascular Atherosclerotic Disease recommend it only in people with increased cardiovascular risk. The benefit of aspirin in patients with established cardiovascular disease outweighs the risk of bleeding. This benefit is due to the anti-inflammatory and anti-platelet effect, which reduces the risk of atherothrombosis, but with the risk of bleeding, particularly in individuals susceptible to bleeding. However, the role of this medication as primary prevention in individuals without established cardiovascular disease is controversial especially if they are at risk of bleeding. Despite the recommendations of the ACC/AHA and the European guidelines aspirin continues to be auto medicated for a large number of subjects. In this communication we discuss the ACC / AHA Guidelines, the ASCEND study in diabetics, the ASPREE in healthy elderly and the ARRIVE in patients with moderate to high risk and others to serve as an alarm to general practitioners and specialists, in order for them to inquire about the use of aspirin in their patients, and at the same time discuss the balance between the harm and the benefits, particularly in elderly patients and those at risk of bleeding. It is suggested to conduct a study to obtain evidence of the number of people who take self-medicated aspirin, follow up, and evolution once these recommendations are widely known and implemented(AU)