Proprotein convertase subtilisin/kexin type 9 inhibitors in peripheral artery disease:A review of efficacy,safety,and outcomes

Peripheral artery disease(PAD)is a common condition characterized by atherosclerosis in the peripheral arteries,associated with concomitant coronary and cerebrovascular diseases.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors are a class of drugs that have shown potential in hypercholesterolemic patients.This review focuses on the efficacy,safety,and clinical outcomes of PCSK9 inhibitors in PAD based on the literature indexed by PubMed.Trials such as FOURIER and ODYSSEY demonstrate the efficacy of evolocumab and alirocumab in reducing cardiovascular events,offering a potential treatment option for PAD patients.Safety evaluations from trials show few adverse events,most of which are injection-site reactions,indicating the overall safety profile of PCSK9 inhibitors.Clinical outcomes show a reduction in cardiovascular events,ischemic strokes,and major adverse limb events.However,despite these positive findings,PCSK9 inhibitors are still underutilized in clinical practice,possibly due to a lack of awareness among care providers and cost concerns.Further research is needed to establish the long-term effects and cost-effectiveness of PCSK9 inhibitors in PAD patients.

Association of Remnant-like Particle Cholesterol with Major Adverse Cardiovascular Events in Subjects with Different Levels of Proprotein Convertase Subtilisin/Kexin 9:A 9.5-year Follow-up Study in a Beijing Community Population

Objective::The purpose of this study was to determine the relationship between remnant-like particle cholesterol(RLP-C)and major adverse cardiovascular events(MACEs)in patients with different levels of proprotein convertase subtilisin/kexin 9(PCSK9).Methods::From September 2007 to January 2009,1,859 subjects in Pingguoyuan communities in Beijing were initially screened.After excluding those with bedridden status,mental illness,severe systemic diseases,and missing data,1,680 subjects were recruited for follow up.All recruited subjects were followed up from February 2013 to September 2013(181 subjects were lost to follow-up)and from June 2017 to September 2018(174 subjects were lost to follow up).Finally,1,325 subjects were included in the study.General demographic characteristics,lifestyle and behaviors,disease history and use of medication was collected.Levels of total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,fast blood glucose,RLP-C,low-density lipoprotein triglycerides and PCSK9 were measured.The levels of RLP-C(low:RLP-C≤157 mg/L;high:RLP-C>157 mg/L)and PCSK9(low:PCSK9≤135.87μg/L;high:PCSK9>135.87μg/L)were represented using quartiles.Subjects were categorized into 4 groups according to their RLP-C and PCSK9 levels:Q4,high levels of RLP-C with high levels of PCSK9;Q3,high levels of RLP-C with low levels of PCSK9;Q2,low levels of RLP-C with high levels of PCSK9;and Q1,low levels of RLP-C with low levels of PCSK9.The association of RLP-C with MACEs in subjects with different PCSK9 levels was evaluated.Results::After a median follow-up of 9.5 years,1,325 subjects were included in the study and a total of 191 MACEs had occurred.The incidence of MACEs was higher in the RLP-C>157 mg/L group than the RLP-C≤157 mg/L group(18.40%vs.10.42%).Cox proportional hazards regression model analysis showed that increased RLP-C levels were associated with an increased risk of MACEs(hazard ratio:1.405;95%confidence interval:1.005-1.964;P<0.005).The incidence of MACEs was higher in the high RLP-C/PCSK9 group vs.the low RLP-C/PCSK9 group(20.68%vs.8.76%).Cox proportional hazards regression model analysis showed that RLP-C was associated with an increased risk of MACEs in subjects with high PCSK9 levels independent of traditional risk factors(hazard ratio:1.791;95%confidence interval:1.168-2.825;P=0.001),but not in those with low PCSK9 levels.Conclusions::RLP-C was identified as a risk factor for MACEs,particularly in subjects with high PCSK9 levels.Lowering PCSK9 levels may reduce residual risk in subjects with elevated plasma RLP-C levels.

Effects of proprotein convertase subtilisin/kexin type-9 inhibitors on fatty liver

BACKGROUND Many studies have investigated the progression of nonalcoholic fatty liver disease(NAFLD)and its predisposing risk factors,but the conclusions from these studies have been conflicting.More challenging is the fact that no effective treatment is currently available for NAFLD.AIM To determine the effects of proprotein convertase subtilisin/kexin type-9(PCSK9)inhibitors on fatty infiltration of the liver.METHODS This retrospective,chart review-based study was conducted on patients,18-yearold and above,who were currently on PCSK9 inhibitor drug therapy.Patients were excluded from the study according to missing pre-or post-treatment imaging or laboratory values,presence of cirrhosis or rhabdomyolysis,or development of acute liver injury during the PCSK9 inhibitor treatment period;the latter being due to false elevation of liver function markers,alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Radiographic improvement was assessed by a single radiologist,who read both the pre-and post-treatment images to minimize reading bias.Fatty infiltration of the liver was also assessed by changes in ALT and AST,with pre-and post-treatment levels compared by paired t-test(alpha criterion:0.05).RESULTS Of the 29 patients included in the study,8 were male(27.6%)and 21 were female(72.4%).Essential hypertension was present in 25(86.2%)of the patients,diabetes mellitus in 18(62.1%)and obesity in 15(51.7%).In all,patients were on PCSK9 inhibitors for a mean duration of 23.69±11.18 mo until the most recent ALT and AST measures were obtained.Of the 11 patients who received the radiologic diagnosis of hepatic steatosis,8(72.73%)achieved complete radiologic resolution upon use of PCSK9 inhibitors(mean duration of 17.6 mo).On average,the ALT level(IU/L)decreased from 21.83±11.89 at pretreatment to 17.69±8.00 at posttreatment(2-tailed P=0.042)and AST level(IU/L)decreased from 22.48±9.00 pretreatment to 20.59±5.47 post-treatment(2-tailed P=0.201).CONCLUSION PCSK9 inhibitors can slow down or even completely resolve NAFLD.

The proprotein convertase subtilisin/kexin type 9 geneE670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

Background The association of E670G polymorphism in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and serum lipid profiles is inconsistent in dif- ferent ethnic groups.Bai Ku Yao is a special subgroup of the Yao minority in China.The present study was undertaken association of PCSK9 E670G polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.Methods A total of 649 subjects of Bai Ku Yao and 646 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples.Genotyping of the PCSK9 E670G polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis,and then confirmed by direct sequencing. Results The levels of serum total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C) and apolipoprotein(Apo) AI were lower in Bai Ku Yao than in Han(P【0.01 for all).The frequency of A and G alleles was 98.00%and 2.00%in Bai Ku Yao,and 95.20%and 4.80%in Han(P【0.01);respectively. The frequency of AA,AG and GG genotypes was 95.99%,4.01%and 0%in Bai Ku Yao,and 91.02%, 8.36%and 0.62%in Han(P【0.01);respectively.There were also significant differences in the genotypic and allelic frequencies between n and the ratio of ApoAI to ApoB in Han Chinese but not in Bai Ku Yao were different between the AA and AG/GG genotypes(P【0.05 for all).The G allele carriers had higher serum HDL-C and higher ApoAI to ApoB ratio than the G allele noncarriers.When serum lipid parameters in Han were analyzed according to sex,the G allele carriers had higher serum HDL and ApoAI levels in males (P【0.05),and lower ApoB level and higher ApoAI to ApoB ratio in females(P【0.05 for all).Multiple linear regression analysis showed that serum HDL-C levels were correlated with genotypes in both ethnic groups(P【0.05 each).Serum lipid parameters were also correlated with sex,age,body massindex,alcohol consumption,cigarette smoking,and blood pressure in both ethnic groups(P【0.05-0.001).Conclusions These results suggest that the PCSK9 E670G polymorphism is mainly associated with some serum lipid parameters in the Han population,both gender show different relations to different serum lipid parameters.The G allele carriers might have higher serum lipid profiles than the G allele noncarriers. ormal LDL-C(≤3.20 mmol/L) and high LDL-C subgroups (】 3.20 mmol/L,P【0.01;respectively) in Bai Ku Yao, and between normal ApoB(≤1.14 g/L) and high ApoB subgroups(】 1.14 g/L,P 【 0.01;respectively) in Han.

Proprotein convertase subtilisin/kexin type 9 inhibitor non responses in an adult with a history of coronary revascularization:A case report

BACKGROUND Familial hypercholesterolemia(FH)is an autosomal dominant disorder that is characterized by severely increased low-density lipoprotein(LDL)cholesterol levels.At the same time,elevated LDL levels accelerated the development of coronary heart disease.Several classes of drugs are currently in use to treat FH.Proprotein convertase subtilisin/kexin type 9 inhibitor(PCSK9i)is novel one of these.CASE SUMMARY This manuscript reports a case of FH that responded modestly after treatment with PCSK9i and statin drugs.Of even more concern is that the patient frequently admitted to the hospital during a 12-year follow-up period.Subsequently,we identified a heterozygous mutation,1448G>A(W483X)of the LDL receptor(LDLR)in this patient.The serum levels of PCSK9(proprotein convertase subtilisin/kexin type 9)in the patient was 71.30±26.66 ng/mL,which is close the average level reported in the literature.This LDLR mutation affects LDLR metabolism or structure,which may make it unsuitable for use of PCSK9i.CONCLUSION Our outcome demonstrates that LDLR-W483X represents a partial loss-of-function LDLR and may contribute to PCSK9i ineffective. In the meanwhile, additional measures aretherefore required (particularly with gene sequencing or change the treatment plan) must beinitiated as early as possible. Genetic testing for clinically challenging cases who do not respond toPCSK9i therapy is very helpful.

Changes in proprotein convertase subtilisin/kexin type 9 mRNA expression in rat cortex after cerebral ischemia

Oxidized low density lipoprotein is a risk factor for cerebrovascular disease. Proprotein convertase subtilisin/kexin type 9 （PCSK9） can increase the level of low density lipoprotein. Therefore, this study assumed that PCSK9 plays important roles in ischemic cerebrovascular disease. The present study established transient focal cerebral ischemia models after 100 minutes of middle cerebral artery occlusion. In situ hybridization demonstrated that PCSK9 mRNA expression increased gradually with prolonged reperfusion time in ischemic cortices. This indicated that transient focal cerebral ischemia upregulated PCSK9 mRNA expression in ischemic cortices.

早期启用前蛋白转化酶枯草杆菌蛋白酶/kexin 9抑制剂对急诊冠状动脉介入中长期预后的影响

目的:探讨早期启用前蛋白转化酶枯草杆菌蛋白酶/kexin 9型(proprotein convertase subtilisin/kexin type 9 serine protease,PCSK9)抑制剂治疗急诊冠状动脉介入患者的临床疗效和安全性。方法:选取2021年6月至2022年6月,我院心血管内科收治的急诊冠状动脉介入患者128例,随机分为观察组和对照组,每组各64例。观察组患者入院后手术前即开始启用PCSK9抑制剂,此后每次75mg皮下注射,每2周1次;对照组,按照指南推荐,待6周后评估LDL-C或非HDL-C水平后,评估是否加用依折麦布或启用PCSK9抑制剂。随访时间为12个月。评估发病6周、6个月及12个月后血脂水平及达标情况及主要心血管不良事件(main adverse cardiovascular events,MACE),包括全因死亡、急性心肌梗死、不稳定性心绞痛、心源性猝死及缺血性卒中,和药物不良事件,包括谷丙转氨酶升高超过正常值上限的3倍以上、肌痛。结果:与对照组相比,观察组治疗6周、6个月及12个月时血清TC、TG、LDL-C改善更为显著(P<0.05)。使用PCSK9抑制剂强化降脂治疗6周后,观察组LDL-C达标率为98.4%,高于对照组的56.3%(P<0.001)。治疗12个月后,两组间血脂达标率,差异有统计学意义(100.0%vs.84.3%,P=0.001),观察组的MACE显著减少(20.3%vs.10.9%,P=0.04)。两组药物不良反应事件差异无统计学意义(P>0.05)。结论:急性冠状动脉综合征发病后早期启用PCSK9抑制剂可以及早使血脂管理达标,改善急诊冠状动脉介入患者中长期预后,安全性较好。

前蛋白转化酶枯草溶菌素-kexin 9型抑制剂对血管内皮的保护作用机制研究进展

前蛋白转化酶枯草溶菌素-kexin9型抑制剂(PCSK9抑制剂)不仅具有良好的降脂作用,还具有改善心血管结局、减轻氧化应激及改善血管内皮等多效性作用。近年来,PCSK9抑制剂的不断研发为心血管疾病治疗提供了新思路,本文就PCSK9抑制剂的多效性作用机制研究,尤其是对于血管内皮功能的作用机制研究予以综述。

前蛋白转化酶枯草杆菌蛋白酶/Kexin9型在心肌梗死及缺血再灌注中的研究进展

目前,前蛋白转化酶枯草杆菌蛋白酶/Kexin9型(PCSK9)抑制剂已经作为一种快速、有效降低低密度脂蛋白胆固醇(LDL-C)的药物广泛地应用在临床领域,除了可以通过调节LDL-C来影响动脉粥样硬化的进程外。临床数据表明,PCSK9在缺血心脏中上调,并且降低PCSK9的表达对梗死范围、梗死后炎症和重构以及缺血再灌注后的心功能不全存在益处。在心血管风险增加的受试者中,PCSK9抑制与心肌梗死、中风和冠状动脉血运重建的发生率降低以及内皮功能改善相关。本文综述了在心肌梗死以及心梗后的缺血再灌注中PCSK9起到的作用。

急性心肌梗死患者血浆前蛋白转化酶枯草溶菌素9水平的影响因素研究

背景前蛋白转化酶枯草溶菌素9(PCSK9)对脂质代谢起到重要调节作用,急性心肌梗死患者血浆PCSK9水平的影响因素尚未完全阐明。目的了解急性心肌梗死患者血浆PCSK9水平的影响因素。方法连续纳入2010—2018年于北京大学第一医院心血管内科入院诊断为急性心肌梗死的患者。基线信息采集患者入院时电子病历系统中的现病史、既往史、体格检查相关信息,检测基线血浆PCSK9水平。影响因素分析采用单因素及多因素线性回归模型,通过LASSO法进行筛选并纳入多因素线性回归模型。结果共入选996例急性心肌梗死患者,其中37例患者因留存血样容量不足无PCSK9检测结果,共959例患者纳入分析,PCSK9水平为543.1(425.4,692.1)ng/mL。多因素回归分析结果显示,性别是影响急性心肌梗死患者PCSK9水平最大的因素(标准化回归系数为0.13),其余对PCSK9水平影响较大的因素依次为:心房颤动病史(标准化回归系数为0.09)、白细胞计数(标准化回归系数为0.07)及血尿酸水平(标准化回归系数为0.07)。结论在急性心肌梗死患者中,性别、心房颤动病史、白细胞计数及血尿酸水平与血浆PCSK9水平显著独立相关。

动态动脉硬化指数联合血清肿瘤坏死因子受体相关因子6、前蛋白转化酶枯草溶菌素9对急性分水岭脑梗死病人的预后价值

目的探究动态动脉硬化指数(AASI)联合血清肿瘤坏死因子受体相关因子6(TRAF6)、前蛋白转化酶枯草溶菌素9(PCSK9)对急性分水岭脑梗死(CWI)病人的预后价值。方法选取2019年8月至2021年8月保定市第二中心医院收治的96例急性CWI病人为研究组,另取同期体检健康者80例为对照组。收集病人一般临床资料,并对研究组和对照组的血清TRAF6、PCSK9水平及AASI进行检测;根据研究组病人预后情况将其分为预后良好组(67例)和预后不良组(29例),多因素logistic回归分析急性CWI病人预后的影响因素;绘制AASI与血清TRAF6、PCSK9对急性CWI病人预后评估的受试者操作特征曲线(ROC曲线)。结果研究组血清TRAF6(1.48±0.34)µg/L、PCSK9(97.25±14.25)µg/L水平及AASI(0.56±0.15)高于对照组(0.87±0.19)µg/L、(82.78±9.17)µg/L、(0.36±0.11)(P<0.05)。预后良好组与预后不良组年龄、美国国立卫生研究院卒中量表(NIHSS)评分、空腹血糖、狭窄程度及血管斑块性质差异有统计学意义(P<0.05)。预后不良组血清TRAF6(1.77±0.37)µg/L、PCSK9(104.82±17.93)µg/L水平及AASI(0.62±0.12)高于预后良好组(1.35±0.21)µg/L、(93.97±12.65)µg/L、0.53±0.09(P<0.05)。多因素logistic回归分析结果显示NIHSS评分、狭窄程度、血管斑块性质、AASI、血清TRAF6、PCSK9水平是急性CWI病人预后的影响因素(P<0.05)。AASI联合血清TRAF6、PCSK9预测急性CWI病人预后的AUC是0.92,灵敏度为93.10%,特异度为76.12%,Youden指数为0.69,优于AASI、TRAF6、PCSK9各自单独预测(P<0.05)。结论急性CWI病人血清TRAF6、PCSK9水平显著升高,联合AA-SI对病人的预后状况具有较高的预测效能,可为临床的合理干预和改善病人预后提供依据。

血清PCSK9水平对急性心肌梗死患者PCI术后MACE的预测价值

目的:探讨血清前蛋白转化酶枯草溶菌素9(PCSK9)水平对急性心肌梗死(AMI)患者经皮冠状动脉介入(PCI)术后主要不良心血管事件(MACE)的预测价值。方法:将2016年5月~2020年8月本院收治的585例行PCI术的AMI患者纳入研究。收集患者一般资料和术前血清PCSK9水平。根据术后1年MACE发生情况,患者被分为MACE组(152例)与无MACE组(433例)。分析血清PCSK9水平与血脂的相关性,及AMI患者PCI术后1年发生MACE的影响因素,并分析血清PCSK9水平对AMI患者PCI术后1年发生MACE的预测价值。结果:术后随访1年,MACE发生率为25.98%(152/585)。与无MACE组比较,MACE组术前Gensini评分、年龄≥60岁、多个梗死部位、病变支数≥2支、高血压、糖尿病、高脂血症、LVEF<50%、术后慢血流/无复流比例、血清PCSK9水平[51.95(46.82,56.58)ng/ml比72.24(62.37,73.88)ng/ml]均显著升高,P均<0.01。Spearman相关性分析显示,AMI患者血清PCSK9水平与总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平呈显著正相关(r=0.728,0.784,P=0.014,0.008)。多因素Logistic回归分析显示年龄≥60岁、术前Gensini评分、多个梗死部位、病变支数≥2支、高血压、糖尿病、高脂血症、LVEF<50%、术后慢血流/无复流、血清PCSK9水平均为AMI患者PCI术后1年内发生MACE的独立危险因素(OR=2.757~6.888,P均<0.01)。ROC曲线分析显示,血清PCSK9水平预测AMI患者PCI术后1年内发生MACE的截断值为59.11ng/ml,灵敏度、特异度、AUC(95%CI)分别为88.72%、77.37%、0.871(0.841~0.897),说明血清PCSK9水平对其具有较好的预测价值。结论:血清PCSK9高水平可增加AMI患者PCI术后MACE的发生风险,且对其具有较好的预测价值。

前蛋白转化酶枯草杆菌蛋白酶Kexin-9抑制剂在降脂治疗中的研究进展

前蛋白转化酶枯草杆菌蛋白酶Kexin-9(PCSK9)已成为调节低密度脂蛋白胆固醇(LDL-C)水平的重要靶点,PCSK9抑制剂能显著降低血浆LDL-C水平,他汀类药物也可降低LDL-C水平但会导致PCSK9水平升高。临床试验已证实他汀类药物与PCSK9抑制剂联合使用的疗效和安全性。尽管不同类型的PCSK9抑制剂作用方式不同,但其在患者中发挥的效果是一致的,目前仍在进行的临床试验将进一步证明其安全性和降低心血管风险的作用。

PCSK9:心血管钙化的新治疗靶点?

前蛋白转化酶枯草溶菌素9(PCSK9)是分泌型丝氨酸蛋白酶家族的第9个成员,由692个氨基酸组成,它能与低密度脂蛋白受体(LDLR)结合,导致循环中的低密度脂蛋白胆固醇(LDLC)水平升高,从而引发诸多心血管疾病,其与心血管钙化的关系近来受到关注。心血管钙化是心血管系统的一种异位矿化,以血管壁和血管瓣膜中产生矿物质沉积为主要特征,其发病机制与脂蛋白含量、血小板活性、基质囊泡(MV)释放及炎症反应有关,PCSK9可能通过上述途径参与心血管钙化的发生。因此,本文对PCSK9与心血管钙化之间的关系进行综述,并着重介绍了PCSK9通过不同途径影响心血管钙化的具体作用,有助于建立PCSK9在血管生物学中的新作用,并确定心血管钙化治疗的新分子机制。

前蛋白转化酶枯草溶菌素9抑制剂作为一级预防治疗对兔动脉粥样硬化斑块发生与进展的影响

目的探讨前蛋白转化酶枯草溶菌素9抑制剂作为一级预防治疗对兔动脉粥样硬化斑块发生与进展的影响。方法选取健康纯种雄性新西兰白兔30只,随机分为对照组、模型组和依洛尤单抗组,每组10只。对照组普通饲料喂养;模型组给予高脂饲料喂养并对右颈动脉内膜进行损伤。依洛尤单抗组在模型组基础上给予依洛尤单抗皮下注射。采集兔外周血,检测各组血脂水平。比较各组血管病理切片。采用免疫组织化学染色法评估CD68、CD147、基质金属蛋白酶9在斑块内的表达。结果模型组、依洛尤单抗组在高脂饮食13周后低密度脂蛋白胆固醇、总胆固醇、甘油三酯水平均高于干预前,且均高于对照组;模型组低密度脂蛋白胆固醇、总胆固醇、甘油三酯水平均高于依洛尤单抗组[(19.1±1.6)mmol/L比(11.2±1.3)mmol/L,(22.2±2.4)mmol/L比(13.1±2.7)mmol/L,(5.8±0.9)mmol/L比(4.7±0.5)mmol/L],差异均有统计学意义(均P<0.05)。对照组未见斑块形成,而模型组和依洛尤单抗组均可见颈动脉斑块形成,模型组斑块内膜巨噬细胞及泡沫细胞丰富,斑块内部可见较大脂质核心,纤维帽薄,形成典型的易损斑块;依洛尤单抗组多表现为内膜增生,较模型组斑块体积及狭窄程度较小,同时CD147、基质金属蛋白酶9表达较模型组少。结论依洛尤单抗的早期干预治疗,可有效控制低密度脂蛋白胆固醇、总胆固醇、甘油三酯水平,显著减小动脉粥样硬化斑块体积及狭窄程度,减轻斑块内脂质沉积,降低炎症反应,使斑块更加稳定,在冠状动脉粥样硬化性心脏病的形成中有着一级预防治疗的意义。

血清PCSK9、ICAM-1与ACS合并糖尿病患者PCI术后心肌损伤及预后的关系

目的探讨血清前蛋白转化酶枯草溶菌素9(PCSK9)、细胞间黏附分子-1(ICAM-1)与急性冠脉综合征(ACS)合并糖尿病患者经皮冠状动脉介入(PCI)术后心肌损伤及预后的关系。方法将2020年1月至2022年3月该院收治的58例ACS合并糖尿病患者纳入研究。患者行PCI手术后,根据是否发生心肌损伤,分为心肌损伤组(n=24)和心肌未损伤组(n=34)。对患者术后进行12个月的随访,根据是否发生主要不良心血管事件(MACE)分为预后不良组(n=20)和预后良好组(n=38)。比较不同组别的患者血清PCSK9、ICAM-1水平;采用受试者工作特征(ROC)曲线评估血清PCSK9、ICAM-1水平对ACS合并糖尿病患者PCI术后心肌损伤及预后不良的预测价值。结果心肌损伤组患者血清PCSK9、ICAM-1水平高于心肌未损伤组(P<0.05)。预后不良组患者血清PCSK9、ICAM-1水平高于预后良好组(P<0.05)。ROC曲线分析显示,血清PCSK9联合血清ICAM-1的预测价值最高,其用于预测ACS合并糖尿病患者PCI术后心肌损伤及预后不良的曲线下面积(AUC)最大,分别为0.865和0.820。结论血清PCSK9、ICAM-1水平与ACS合并糖尿病患者PCI术后心肌损伤及预后密切相关,两者联合检测对患者心肌损伤及预后不良的预测价值最高。

MRI动态增强成像联合血清PCSK9、TM4SF1诊断乳腺癌的临床价值

目的探讨磁共振成像(MRI)动态增强联合血清前蛋白转化酶枯草溶菌素9(PCSK9)、四跨膜蛋白超家族成员1(TM4SF1)诊断乳腺癌的临床价值。方法选取2020年2月至2022年6月本院收治的乳腺癌患者102例作为乳腺癌组,另选同期乳腺良性肿瘤患者102例,作为对照组,两组患者均进行MRI动态增强成像检查;采用酶联免疫吸附法(ELISA)检测血清PCSK9、TM4SF1水平;受试者工作特征(ROC)曲线分析血清PCSK9、TM4SF1对乳腺癌的临界诊断点;采用四格表分析MRI动态增强成像联合血清PCSK9、TM4SF1对乳腺癌的诊断价值。结果乳腺癌病灶部位较良性组相比其癌旁组织分界不清,边缘表现不规则,强化不均匀。乳腺癌组血清PCSK9、TM4SF1水平显著高于良性组(P<0.05)。根据ROC曲线得知,血清PCSK9诊断乳腺癌的AUC为0.929,血清TM4SF1诊断乳腺癌的AUC为0.880,二者联合诊断乳腺癌的AUC为0.959。MRI动态增强成像在乳腺癌诊断中准确度为89.22%,灵敏度为84.31%,特异度为94.12%;PCSK9在乳腺癌诊断中准确度为84.31%,灵敏度为78.43%,特异度为90.20%;TM4SF1在乳腺癌诊断中准确度为83.82%,灵敏度为77.45%,特异度为90.20%;三者联合检测在乳腺癌诊断中准确度为90.24%,灵敏度为88.24%,特异度为92.23%。MRI动态增强成像、血清PCSK9、TM4SF1与肿瘤直径、TNM分期、淋巴结转移和分类风险有关(P<0.05)。结论乳腺癌血清PCSK9、TM4SF1水平均升高,MRI动态增强成像联合血清PCSK9、TM4SF1可提高乳腺癌的诊断价值。

天然化合物抑制前蛋白转化酶枯草溶菌素9的作用机制研究进展

动脉粥样硬化(atherosclerosis, AS)是一种复杂的慢性进行性动脉疾病,被视为全球死亡的重要原因。高水平的血浆低密度脂蛋白胆固醇(low density lipoprotein-cholesterol, LDL-C)是AS发生和发展的关键危险因素。血浆中循环的前蛋白转化酶枯草溶菌素9 (proprotein convertase subtilisin/kexin type 9, PCSK9)是一种肝细胞合成的丝氨酸蛋白酶,是低密度脂蛋白受体(low density lipoprotein receptor,LDLR)的关键调节因子,在控制血浆LDL-C水平方面发挥着关键作用,它通过与肝脏LDLR结合,形成PCSK9-LDLR复合物导致LDLR在溶酶体中降解,并减少肝细胞膜表面的LDLR的数量,进而导致血浆LDL-C水平升高。目前,临床常用他汀类降脂药物,如阿托伐他汀调节LDL-C水平,延缓AS,但药物起效慢,单一应用难以达到理想的效果,且会在不同程度上产生不良影响。因此, PCSK9是一种新的降低胆固醇的治疗靶点。本综述旨在阐明调控PCSK9的途径及改善AS的天然化合物的研究现状和潜在的治疗意义,以期为防治AS提供参考。

前蛋白转化酶枯草溶菌素9介导动脉粥样硬化炎症反应及中医药干预的研究进展

“胆固醇学说”奠定了动脉粥样硬化性心血管疾病的治疗基础,但研究证明“炎症反应学说”是有关动脉粥样硬化(AS)的另一研究热点,也是AS干预的潜在靶点。前蛋白转化酶枯草溶菌素9(PCSK9)具有脂质调节和炎症反应介导的多效性,可通过脂质驱动炎症反应,同时也是一种独立的炎症介质参与AS的发生,PCSK9的炎症反应效应可能是中医药治疗AS的重要靶点之一。中药及其提取物(槲皮素、盐酸小檗碱、绞股蓝苷、姜黄素、10-脱氢姜二酮和甘蔗原素、银杏内酯B、柚皮苷和橙皮苷等)、中药复方(首参颗粒、芪蛭通脉颗粒等)对PCSK9有抑制作用,是PCSK9药物研究和发掘的一个重要方向。

血清前蛋白转化酶枯草溶菌素9和脂多糖对老年非瓣膜性心房颤动患者心脑血管病死亡的预测价值分析

目的探讨血清前蛋白转化酶枯草溶菌素9(PCSK9)、脂多糖对老年非瓣膜性心房颤动(NVAF)患者心脑血管病死亡的预测价值。方法选取2016年10月至2020年12月海南省海口市人民医院收治的老年NVAF患者575例,随访3年根据是否发生心脑血管病死亡分为死亡组(74例)和存活组(501例),采用酶联免疫吸附试验法检测血清PCSK9、脂多糖水平。通过多因素Logistic回归分析老年NVAF患者心脑血管病死亡的因素,受试者工作特征(ROC)曲线分析血清PCSK9、脂多糖水平对老年NVAF患者心脑血管病死亡的预测价值。结果随访3年,575例老年NVAF患者心脑血管病死亡率为12.9%(74/575)。死亡组血清PCSK9、脂多糖水平均高于存活组(均P<0.001)。多因素Logistic回归分析显示,年龄增加、CHA 2DS 2-VASc评分增加、急性心肌梗死、卒中/短暂性脑缺血发作、心力衰竭和PCSK9升高、脂多糖升高为老年NVAF患者心脑血管病死亡的独立危险因素(均P<0.05)。ROC曲线显示,血清PCSK9、脂多糖水平联合预测老年NVAF患者心脑血管病死亡的曲线下面积为0.873,大于血清PCSK9、脂多糖水平单独预测的0.781、0.795(均P<0.001)。结论血清PCSK9、脂多糖水平升高是老年NVAF患者心脑血管病死亡的独立危险因素,血清PCSK9、脂多糖水平联合对老年NVAF患者心脑血管病死亡的预测价值较高。