Atherosclerosis(AS)remains a major contributor to cardiovascular disease(CVD)mortality worldwide.Its development involves dysregulated lipid handling,persistent vascular inflammation,and endothelial cell(EC)dysfunctio...Atherosclerosis(AS)remains a major contributor to cardiovascular disease(CVD)mortality worldwide.Its development involves dysregulated lipid handling,persistent vascular inflammation,and endothelial cell(EC)dysfunction,influenced by genetic,environmental,and lifestyle factors.Increasing evidence highlights a pivotal role of endoplasmic reticulum(ER)stress as a molecular link between lipid dysregulation and inflammatory signaling in AS pathogenesis.ER stress is triggered by modified LDL,oxidized lipids,hyperhomocysteinemia,oxidative stress(OS),and disrupted calcium(Ca^(2+))homeostasis,leading to activation of the unfolded protein response(UPR).Core UPR mediators-inositol-requiring enzyme 1(IRE1),protein kinase RNA-like ER kinase(PERK),and activating transcription factor 6(ATF6)-initially act to restore ER homeostasis but,when persistently activated,may drive pro-inflammatory cytokine production,apoptosis,and plaque destabilization.The aim of this review is to critically synthesize primary research evidence on ER stress as amediator of lipid-driven inflammation in ECs,macrophages,and vascular smooth muscle cells(VSMCs),emphasizing disease-stage–specific effects.Current debates include whether macrophage ER stress promotes necrotic core expansion vs.apoptosis-mediated clearance,and whether ER stress in ECs is initially protective or primarily pathogenic.Emerging therapeutic strategies targeting ER stress are summarized,including chemical chaperones,AMPK activators,and natural compounds.We highlight the importance of lipid-and inflammation-specific ER stress modulation,noting limitations such as off-target effects and poor bioavailability that hinder translation.Our goal is to achieve a deeper understanding of the lipid–ER stress–inflammation axis to facilitate the design of therapies that may slow AS progression.展开更多
目的分析急性脑梗死(acute cerebral infarction,ACI)患者小而密低密度脂蛋白(small dense low-density lipoprotein,sd-LDL)及脂蛋白(a)水平与颈动脉斑块稳定性的关系。方法回顾性选取2020年2月至2024年2月河北省人民医院收治的老年AC...目的分析急性脑梗死(acute cerebral infarction,ACI)患者小而密低密度脂蛋白(small dense low-density lipoprotein,sd-LDL)及脂蛋白(a)水平与颈动脉斑块稳定性的关系。方法回顾性选取2020年2月至2024年2月河北省人民医院收治的老年ACI患者160例,所有患者行颈部彩色多普勒超声检查,依据颈动脉斑块情况分为无斑块组43例、稳定斑块组56例和不稳定斑块组61例,另取同期河北省人民医院健康体检者40例作为对照组,比较4组临床资料、sd-LDL、脂蛋白(a)水平,评估sd-LDL、脂蛋白(a)水平对不稳定斑块的预测价值。结果与无斑块组比较,稳定斑块组和不稳定斑块组美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)显著升高,不稳定斑块组总胆固醇显著升高,高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)显著降低,对照组NIHSS评分、总胆固醇、三酰甘油、LDL-C显著降低,HDL-C显著升高,差异有统计学意义(P<0.05);与稳定斑块组比较,不稳定斑块组NIHSS评分、LDL-C、sdLDL、脂蛋白(a)显著升高,HDL-C显著降低,对照组脂蛋白(a)显著降低,差异有统计学意义(P<0.05)。Pearson相关性分析显示,sd-LDL、脂蛋白(a)水平与NIHSS评分、总胆固醇、三酰甘油、LDL-C呈显著正相关(P<0.05,P<0.01),与HDL-C呈显著负相关(P<0.01)。二元logistic回归分析显示,NIHSS评分、LDL-C、sd-LDL、脂蛋白(a)是ACI患者颈动脉不稳定斑块形成的危险因素,HDL-C是保护因素(P<0.01)。ROC曲线结果显示,sd-LDL、脂蛋白(a)及联合检测对颈动脉斑块稳定性预测的ROC曲线下面积分别为0.830、0.847、0.921,联合检测的敏感性高于sd-LDL、脂蛋白(a)单项指标检测(93.44%vs 88.52%、86.89%,P=0.000)。结论血浆sd-LDL、脂蛋白(a)水平与ACI患者颈动脉斑块稳定性具有一定关联性,可作为临床相关参考指标。展开更多
目的探讨多系统萎缩(multiple system atrophy,MSA)患者直立性低血压的相关影响因素。方法回顾性选取2024年1月至2025年3月解放军总医院第三医学中心神经内科收治的老年MSA伴直立性低血压患者40例(MSA组),老年非直立性低血压健康体检者4...目的探讨多系统萎缩(multiple system atrophy,MSA)患者直立性低血压的相关影响因素。方法回顾性选取2024年1月至2025年3月解放军总医院第三医学中心神经内科收治的老年MSA伴直立性低血压患者40例(MSA组),老年非直立性低血压健康体检者46例(对照组),比较两组一般临床资料及相关指标,分析MSA患者直立性低血压发生的相关血液因子。结果MSA组维生素D、低密度脂蛋白胆固醇、尿酸水平明显低于对照组,差异有统计学意义(P<0.05,P<0.01)。多因素logistic回归分析显示,维生素D、低密度脂蛋白胆固醇、尿酸水平是MSA伴直立性低血压患者发生的危险因素(OR=0.677,95%CI:0.530~0.864,P<0.01;OR=0.057,95%CI:0.007~0.434,P<0.01;OR=0.972,95%CI:0.954~0.992,P<0.01)。ROC曲线分析显示,维生素D、低密度脂蛋白胆固醇、尿酸水平预测MSA伴直立性低血压发生的最佳截断值分别为21.850μg/L、2.895 mmol/L、274.500μmol/L,敏感性分别为0.848、0.630、0.783,特异性分别为0.792、0.750、0.667。曲线下面积分别为0.862、0.683、0.748。结论监测维生素D、低密度脂蛋白胆固醇、尿酸可能有助于MSA伴直立性低血压的风险评估和管理。展开更多
基金funded by Russian Science Foundation,grant number 25-15-00080.
文摘Atherosclerosis(AS)remains a major contributor to cardiovascular disease(CVD)mortality worldwide.Its development involves dysregulated lipid handling,persistent vascular inflammation,and endothelial cell(EC)dysfunction,influenced by genetic,environmental,and lifestyle factors.Increasing evidence highlights a pivotal role of endoplasmic reticulum(ER)stress as a molecular link between lipid dysregulation and inflammatory signaling in AS pathogenesis.ER stress is triggered by modified LDL,oxidized lipids,hyperhomocysteinemia,oxidative stress(OS),and disrupted calcium(Ca^(2+))homeostasis,leading to activation of the unfolded protein response(UPR).Core UPR mediators-inositol-requiring enzyme 1(IRE1),protein kinase RNA-like ER kinase(PERK),and activating transcription factor 6(ATF6)-initially act to restore ER homeostasis but,when persistently activated,may drive pro-inflammatory cytokine production,apoptosis,and plaque destabilization.The aim of this review is to critically synthesize primary research evidence on ER stress as amediator of lipid-driven inflammation in ECs,macrophages,and vascular smooth muscle cells(VSMCs),emphasizing disease-stage–specific effects.Current debates include whether macrophage ER stress promotes necrotic core expansion vs.apoptosis-mediated clearance,and whether ER stress in ECs is initially protective or primarily pathogenic.Emerging therapeutic strategies targeting ER stress are summarized,including chemical chaperones,AMPK activators,and natural compounds.We highlight the importance of lipid-and inflammation-specific ER stress modulation,noting limitations such as off-target effects and poor bioavailability that hinder translation.Our goal is to achieve a deeper understanding of the lipid–ER stress–inflammation axis to facilitate the design of therapies that may slow AS progression.
文摘目的分析急性脑梗死(acute cerebral infarction,ACI)患者小而密低密度脂蛋白(small dense low-density lipoprotein,sd-LDL)及脂蛋白(a)水平与颈动脉斑块稳定性的关系。方法回顾性选取2020年2月至2024年2月河北省人民医院收治的老年ACI患者160例,所有患者行颈部彩色多普勒超声检查,依据颈动脉斑块情况分为无斑块组43例、稳定斑块组56例和不稳定斑块组61例,另取同期河北省人民医院健康体检者40例作为对照组,比较4组临床资料、sd-LDL、脂蛋白(a)水平,评估sd-LDL、脂蛋白(a)水平对不稳定斑块的预测价值。结果与无斑块组比较,稳定斑块组和不稳定斑块组美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)显著升高,不稳定斑块组总胆固醇显著升高,高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)显著降低,对照组NIHSS评分、总胆固醇、三酰甘油、LDL-C显著降低,HDL-C显著升高,差异有统计学意义(P<0.05);与稳定斑块组比较,不稳定斑块组NIHSS评分、LDL-C、sdLDL、脂蛋白(a)显著升高,HDL-C显著降低,对照组脂蛋白(a)显著降低,差异有统计学意义(P<0.05)。Pearson相关性分析显示,sd-LDL、脂蛋白(a)水平与NIHSS评分、总胆固醇、三酰甘油、LDL-C呈显著正相关(P<0.05,P<0.01),与HDL-C呈显著负相关(P<0.01)。二元logistic回归分析显示,NIHSS评分、LDL-C、sd-LDL、脂蛋白(a)是ACI患者颈动脉不稳定斑块形成的危险因素,HDL-C是保护因素(P<0.01)。ROC曲线结果显示,sd-LDL、脂蛋白(a)及联合检测对颈动脉斑块稳定性预测的ROC曲线下面积分别为0.830、0.847、0.921,联合检测的敏感性高于sd-LDL、脂蛋白(a)单项指标检测(93.44%vs 88.52%、86.89%,P=0.000)。结论血浆sd-LDL、脂蛋白(a)水平与ACI患者颈动脉斑块稳定性具有一定关联性,可作为临床相关参考指标。
文摘目的探讨多系统萎缩(multiple system atrophy,MSA)患者直立性低血压的相关影响因素。方法回顾性选取2024年1月至2025年3月解放军总医院第三医学中心神经内科收治的老年MSA伴直立性低血压患者40例(MSA组),老年非直立性低血压健康体检者46例(对照组),比较两组一般临床资料及相关指标,分析MSA患者直立性低血压发生的相关血液因子。结果MSA组维生素D、低密度脂蛋白胆固醇、尿酸水平明显低于对照组,差异有统计学意义(P<0.05,P<0.01)。多因素logistic回归分析显示,维生素D、低密度脂蛋白胆固醇、尿酸水平是MSA伴直立性低血压患者发生的危险因素(OR=0.677,95%CI:0.530~0.864,P<0.01;OR=0.057,95%CI:0.007~0.434,P<0.01;OR=0.972,95%CI:0.954~0.992,P<0.01)。ROC曲线分析显示,维生素D、低密度脂蛋白胆固醇、尿酸水平预测MSA伴直立性低血压发生的最佳截断值分别为21.850μg/L、2.895 mmol/L、274.500μmol/L,敏感性分别为0.848、0.630、0.783,特异性分别为0.792、0.750、0.667。曲线下面积分别为0.862、0.683、0.748。结论监测维生素D、低密度脂蛋白胆固醇、尿酸可能有助于MSA伴直立性低血压的风险评估和管理。
