BackgroundInsulin resistance (IR) is recognized as a potential modifiable risk factor for cognitive decline, but findings within Asian populations have been inconsistent. Given the high prevalence of dementia and its substantial economic burden in China, large-scale longitudinal studies are essential to elucidate the complex relationship between IR and cognitive function.MethodsThis longitudinal cohort study included 8,734 middle-aged and older adults (median age: 58 years; 53.6% females) from the China Health and Retirement Longitudinal Study (CHARLS), followed from 2011 to 2018. Estimated glucose disposal rate (eGDR) was used to assess IR and was calculated using waist circumference, hypertension status, and HbA1c levels. Participants were categorized into tertiles based on eGDR levels (Tertile 1: lowest; Tertile 3: highest). Cognitive function was calculated as the sum of episodic memory and executive function scores, which was then standardized to a Z-score. Linear mixed-effects models and dose-response analyses were performed to evaluate the association between baseline eGDR and cognitive changes in the total population and stratified by sex.ResultsHigher eGDR levels were significantly associated with slower global cognitive decline (Tertile 3 vs. Tertile 1: β = 0.007; 95% CI: 0.000–0.014; P = 0.047). This association was stronger in females (Tertile 3 vs. Tertile 1: β = 0.011; 95% CI: 0.002–0.021; P = 0.021), while no significant association was observed in males. Dose-response analyses indicated a linear positive relationship between baseline eGDR and global cognitive function in the total population and in females, but not in males. Similar patterns were found for episodic memory and executive function, with significant associations predominantly in females.ConclusionHigher eGDR was significantly associated with slower cognitive decline, particularly among women. These findings underscore the potential of eGDR as a marker for identifying and mitigating cognitive decline and highlight the importance of sex-specific strategies to address insulin resistance and promote cognitive health.

Endothelial progenitor cells (EPCs) are undifferentiated cells with the capacity to mature into endothelial cells (ECs). EPCs have garnered considerable attention in the fields of regenerative medicine and cardiovascular therapy, owing to their pivotal role in neovascularization and vascular repair. Nonetheless, numerous challenges and questions persist regarding the translational research and practical application of EPCs. This review aims to examine the varying definitions of EPCs, their classification, extraction methods, and sources. It will also address the optimization of cultivation techniques for EPCs and the reprogramming of EPCs into induced pluripotent stem cells (iPSCs). Furthermore, the review will delve into the role of EPCs in cardiovascular diseases (CVD), septic shock, and rheumatic immune conditions, as well as their implications in connective tissue diseases (CTDs) and skin soft tissue regeneration. Finally, the article will discuss future research prospects for EPCs, aiming to engage and inspire readers.

Chronic psychological stress is closely related to myocardial diseases, but the pathological processes and related mechanisms are not yet clear. In this study, 5 batches of animal experiments are conducted to reveal the pathological process of chronic psychological stress on the heart, and found that cardiomyocyte hypertrophy is an early manifestation of cardiac damage. Furthermore, it is discovered that corticosterone and glucocorticoid receptor (GR) play an important role in mediating this phenomenon. Additionally, a new direct target gene of GR, Lama5, is identified and confirmed in vivo and in vitro that the corticosterone-GR-LAMA5 axis is a significant pathway mediating chronic psychological stress-induced cardiomyocyte hypertrophy. Moreover, the potential of LAMA5 is validated as a biomarker for myocardial hypertrophy and impaired cardiac function in patients with depression. In summary, a novel hypertrophy-related gene, Lama5 has been identified, that may play an important role in chronic psychological stress-induced cardiomyocyte hypertrophy.

Sepsis is a life-threatening condition with high mortality, underscoring the urgent need for effective therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) analysis using plasma protein data from the FinnGen, UKB-PPP, and deCODE cohorts to identify proteins causally associated with sepsis. The analysis included 16,074 cases and 363,227 controls in FinnGen and 11,643 cases and 474,841 controls in the UK Biobank, spanning four exposure-outcome combinations. Proteins were prioritized based on a false discovery rate <0.05 in one combination and p < 0.05 in another. Colocalization and phenome-wide association studies (PheWAS) were performed to evaluate causality and potential off-target effects. Three proteins─dual specificity phosphatase 13 (DUSP13), inhibin beta C chain (INHBC), and toll-like receptor 1 (TLR1)─showed strong evidence of colocalization with sepsis risk. PheWAS confirmed broader disease associations for DUSP13 and TLR1, while INHBC showed no significant adverse associations and is considered druggable. TLR1 is currently under clinical investigation. ELISA-based experimental validation in 20 sepsis patients and 20 controls demonstrated elevated serum levels of DUSP13 and INHBC and reduced levels of TLR1 in sepsis. These findings identify DUSP13, INHBC, and TLR1 as promising therapeutic targets for sepsis, supported by genetic, phenotypic, and experimental evidence.

Chromatin regulators are indispensable upstream epigenetic regulators.The emergence and progression of atherosclerosis has been demonstrated to be influenced by smooth muscle-related chromatin regulators, such as ZEB2 and MAFF. However, specific chromatin regulators and their possible roles have not been clarified. Information was gathered from 51 patients diagnosed with coronary artery disease (CAD) and 50 individuals in good health from the GEO database. 440 genes were identified as having differential expression across the two datasets, and these genes were linked to cellular reactions. Enrichment of pathways related to histone modification and transcriptional regulatory factors was observed in GO and KEGG analyses. Four machine learning models (RF, SVM, GLM, and XGB) were developed using the expression profiles of 440 chromatin-associated genes in the CAD cohort to pinpoint genes with significant diagnostic potential. After evaluating residuals, root mean square errors, receiver operating characteristic curves, and immune-infiltration, four key genes (HCFC1, RNF8, TNP1, and SET) were identified. Gene expression in different blood vessel levels in atherosclerotic plaques in a mouse model of coronary artery disease showed significant variations. The gene expression levels in macrophages aligned with clinical data from the GEO database as expected. This discovery is crucial for future analysis and the prediction of drug and miRNA targets. In conclusion, we found that the four hub genes are important in the mechanism of CAD. These findings provide new ideas for the study of potential epigenetic predictive markers and therapeutic targets to be used in determining a treatment strategy for CAD.

Abstract The lateral pressure exerted by blood on the vessel wall, called low oscillating shear stress(OSS), destroys the endothelial cell barrier function through a process called EndMT and promotes the occurrence of atherosclerosis. The specific mechanism by which OSS regulates EndMT is still unclear. Inhibitor of differentiation 1 (ID1) is controlled by shear stress as an essential force-sensitive factor, and little is known about the effect of ID1 on EndMT in OSS-mediated atherosclerosis. This study investigated the impact of ID1 inhibitors on OSS-mediated EndMT in ApoE−/− mice and TGF-β1-induced human aortic endothelial cells (HAECs). First, we found that the expression of ID1 was down-regulated. At the same time, EndMT and plaque formation occurred in the ligated left common carotid artery (OSS) compared with the unligated right common carotid artery. Then, our results showed that the ID1 inhibitor AGX51 attenuated EndMT in atherosclerosis plaques in OSS mice. However, in vitro studies show that ID1 is upregulated in TGF-β1-treated HAECs and induces EndMT.sh-ID1 or AGX51 to inhibit the EndMT process and restore the migratory ability of endothelial cells. Furthermore, ID1 overexpression promoted the occurrence of EndMT.In addition, inhibition of ID1 may inhibit OSS-induced EndMT by regulating EndMT-specific transcription factors Snail and Wnt/β-catenin signalling pathway in vivo and in vitro by Immunohistochemistry and Western blot. These results suggest that ID1 inhibitors regulate the occurrence and development of low oscillating shear stress-mediated EndMT and atherosclerosis by Ctrlling Snail and Wnt/β-catenin signalling pathways.

Cuproptosis-related key genes play a significant role in the pathological processes of acute myocardial infarction (AMI). However, a complete understanding of the molecular mechanisms behind this participation remains elusive. This study was designed to identify genes and immune cells critical to AMI pathogenesis. Based on the GSE48060 dataset (31 AMI patients and 21 healthy persons, GPL570-55999), we identified genes associated with dysregulated cuproptosis and the activation of immune responses between normal subjects and patients with a first myocardial attack. Two molecular clusters associated with cuproptosis were defined in patients with AMI. Immune infiltration analysis showed that there was significant immunity heterogeneity among different clusters. Multiple immune responses were closely associated with Cluster2-specific differentially expressed genes (DEGs). The generalized linear model machine model presented the best discriminative performance with relatively lower residual and root mean square error, and a higher area under the curve (AUC = 0.870). A final two-gene-based generalized linear model was constructed, exhibiting satisfactory performance in two external validation datasets (AUC = 0.719, GSE66360 and AUC = 0.856, GSE123342). Column graph, calibration curve, and decision curve analyses also proved the accuracy of AMI prediction. We also constructed a mouse C57BL/6 model of AMI (3 h, 48 h, and 1 week) and used qRT-PCR and immunofluorescence to detect the expression changes of CBLB and ZNF302. In this study, we present a systematic analysis of the complex relationship between cuproptosis and a first AMI attack, and provide new insights into the diagnosis and treatment of AMI.

Background: Major depressive disorder (MDD) plays a crucial role in the occurrence of heart failure (HF). This investigation was undertaken to explore the possible mechanism of MDD’s involvement in HF pathogenesis and identify candidate biomarkers for the diagnosis of MDD with HF. Methods: GWAS data for MDD and HF were collected, and Mendelian randomization (MR) analysis was performed to investigate the causal relationship between MDD and HF. Differential expression analysis (DEA) and WGCNA were used to detect HF key genes and MDD-associated secretory proteins. Protein–protein interaction (PPI), functional enrichment, and cMAP analysis were used to reveal potential mechanisms and drugs for MDD-related HF. Then, four machine learning (ML) algorithms (including GLM, RF, SVM, and XGB) were used to screen candidate biomarkers, construct diagnostic nomograms, and predict MDD-related HF. Furthermore, the MCPcounter algorithm was used to explore immune cell infiltration in HF, and MR analysis was performed to explore the causal effect of immunophenotypes on HF. Finally, the validation of the association of MDD with reduced left ventricular ejection fraction (LVEF) and the performance assessment of diagnostic biomarkers was accomplished based on animal models mimicking MDD. Results: The MR analysis showed that the MDD was linked to an increased risk of HF (OR = 1.129, p < 0.001). DEA combined with WGCNA and secretory protein gene set identified 315 HF key genes and 332 MDD-associated secretory proteins, respectively. Through PPI and MCODE analysis, 78 genes were pinpointed as MDD-related pathogenic genes for HF. The enrichment analysis revealed that these genes were predominantly enriched in immune and inflammatory regulation. Through four ML algorithms, two hub genes (ISLR/SFRP4) were identified as candidate HF biomarkers, and a nomogram was developed. ROC analysis showed that the AUC of the nomogram was higher than 0.90 in both the HF combined dataset and two external cohorts. In addition, an immune cell infiltration analysis revealed the immune dysregulation in HF, with ISLR/SFRP4 displaying notable associations with the infiltration of B cells, CD8 T cells, and fibroblasts. More importantly, animal experiments showed that the expression levels of ISLR (r = −0.653, p < 0.001) and SFRP4 (r = −0.476, p = 0.008) were significantly negatively correlated with LVEF. Conclusions: The MR analysis indicated that MDD is a risk factor for HF at the genetic level. Bioinformatics analysis and the ML results suggest that ISLR and SFRP4 have the potential to serve as diagnostic biomarkers for HF. Animal experiments showed a negative correlation between the serum levels of ISLR/SFRP4 and LVEF, emphasizing the need for additional clinical studies to elucidate their diagnostic value.

The endothelial-mesenchymal transition (EndMT) is involved in the development of atherosclerosis (AS) and is a key process in vascular endothelial injury. Oxidative stress, inflammation, and apoptosis are common causes of EndMT, and EndMT progression can further accelerate the development of AS. The metabolite trimethylamine Noxide (TMAO) is produced by the gut microbiome and is implicated in the development of several diseases, including diabetes and chronic kidney disease. However, the impact of TMAO on transforming growth factor beta 1 (TGF-beta 1)-induced EndMT remains unclear. We hypothesize that TMAO exacerbates plaque formation and cardiac function impairment by promoting EndMT. Herein, we showed that high serum TMAO levels caused plaque formation, cardiac function damage and haemodynamic changes in ApoE(- /-) mice. In vitro, TMAO upregulated mesenchymal markers and downregulated endothelial markers in HAECs. Furthermore, TMAO increased the migratory capacity of EndMT cells. Mechanistically, we found that PERK downregulation could alleviate TMAOinduced oxidative stress, EndMT, plaque formation and cardiac function damage. Further study showed that activated transcription factor 3 (ATF3), the downstream molecule of protein kinase RNA-like endoplasmic reticulum kinase (PERK), could bind with TGF-beta 1/2 and affect EndMT. Overall, TMAO promotes EndMT, possibly through the PERK-eIF2 alpha-ATF4-CHOP or the PERk-eIF2 alpha-ATF3-TGF-beta signalling pathways.

Chronic heart failure (CHF) can induce chronic kidney disease (CKD), called type 2 cardio-renal syndrome (CRS2). The mechanism is not completely clear, and there is a lack of early warning biomarkers of CKD in the context of CHF. Two CKD, one CHF-PBMC and four CHF-cardiac tissue expression profile datasets were obtained from GEO database. Differential expression analysis and WGCNA were used to detect CKD key genes and CHF-related secreted proteins. Protein-protein interaction (PPI), functional enrichment, and cMAP analysis reveal potential mechanisms and drugs of CHF-related CKD. Five machine learning algorithms were used to screen candidate biomarkers, construct a diagnostic nomogram for CKD and validate it in two external cohorts. Clinical serum samples were collected in our hospital to evaluate the correlation and diagnostic value of biomarkers and CKD. 225 CKD key genes and 316 CHF-related secreted proteins were identified. Four key subgroups, including 204 genes, were identified as CRS2-related pathogenic genes by PPI analysis. Enrichment analysis revealed that the identified subgroups exhibited significant enrichment in cytokine action, immune responses, and inflammatory processes. The cMAP analysis highlighted metiradone as a drug with greater potential for therapeutic intervention for CRS2. Utilizing five machine learning algorithms, three hub genes (CD48, COL3A1, LOXL1) were pinpointed as potential biomarkers for CKD, and a nomogram model was constructed. Receiver operating characteristic analysis demonstrated that the nomogram's area under the curve (AUC) exceeded 0.80 in both the CKD combined dataset and two external cohorts. In addition, the three biomarkers were significantly correlated with the glomerular filtration rate, and the AUC of the model predicting disease progression was 0.944. Furthermore, analysis of immune cell infiltration indicated a correlation between the three biomarkers and the infiltration fraction of macrophages, neutrophils, and other immune cells in CKD. Our clinical cohort validated the expression patterns of three biomarkers in serum, and the diagnostic model achieved an AUC of 0.876. CHF has the potential to facilitate the progression of CKD via the release of cardiac and PBMC secreted proteins. Furthermore, CD48, COL3A1, and LOXL1 have been identified as potential biomarkers for the detection of CKD.

Background:Observational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications. Methods:We identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications. Results:The study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47-0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62-0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed. Conclusions:Our MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications.

Objective. To determine prognostic role of endothelial progenitor cells (EPCs) in intensive care patients with acute myocardial infarction (AMI). Materials and Methods. From December 2018 to July 2021, a total of 91 eligible patients with AMI were consecutively examined in a single intensive care unit (ICU) in China. Patients with a history of acute coronary artery disease were excluded from the study. Samples were collected within 24 hr of onset of symptoms. EPCs, defined as coexpression of CD34+/CD133+ cells or CD133+/CD34+/KDR+, were studied using flow cytometry and categorized by quartiles. Based on the 28-days mortality outcome, the patients were further divided into two groups: death and survival. The study incorporated various variables, including cardiovascular risk factors such as body mass index, hypertension, diabetes, hypercholesterolemia, atherosclerotic burden, and medication history, as well as clinical characteristics such as APACHEⅡscore, central venous-arterial carbon dioxide difference (GAP), homocysteine, creatinine, C-reactive protein, HbAlc, and cardiac index. Cox regression analysis was employed to conduct a multivariate analysis. Results. A total of 91 patients with AMI who were admitted to the ICU were deemed eligible for inclusion in the study. Among these patients, 23 (25.3%) died from various causes during the follow-up period. The counts of EPCs were found to be significantly higher in the survival group compared to the death group (P<0.05). In the univariate analysis, it was observed that the 28-days mortality rate was associated with the several factors, including the APACHEⅡscore (P=0.00), vasoactive inotropic score (P=0.03), GAP (P=0.00), HCY (P=0.00), creatinine (P=0.00), C-reactive protein (P=0.00), HbAlc (P=0.00), CI (P=0.01), quartiles of CD34+/CD133+ cells (P=0.00), and quartiles of CD34+/CD133+/KDR+ cells (P=0.00). CD34+/CD133+/KDR+ cells retained statistical significance in Cox regression models even after controlling for clinical variables (HR: 6.258 × 10−10 and P=0.001). Nevertheless, no significant correlation was observed between CD34+/CD133+ cells and all-cause mortality. Conclusions. The decreased EPCs levels, especially for CD34+/CD133+/KDR+ cells subsets, were an independent risk factor for 28-days mortality in AMI patients.

目的 探讨有恶性肿瘤病史的冠心病患者的病变特点,以及单核细胞/高密度脂蛋白胆固醇比(MHR)与Syntax积分的相关性.方法 回顾性选取2017年2月至2018年9月在宁波市医疗中心李惠利医院行冠状动脉造影检查确诊为冠心病患者,排除既往有冠状动脉支架植入或冠状动脉旁路移植术、合并失代偿性心力衰竭、严重肝肾功能不全、严重血液系统疾病、急性感染的患者,共纳入693例.根据是否合并恶性肿瘤病史将患者分为肿瘤组(合并恶性肿瘤病史)和对照组(不合并恶性肿瘤病史).应用Syntax评分系统评估冠状动脉病变严重程度,并分为Syntax≥23亚组和Syntax＜23亚组.比较两组冠心病患者冠状动脉病变的特点,以及MHR与Syntax积分的关系.结果 肿瘤组47例,最常累及的是消化系统、泌尿系统和呼吸系统.肿瘤组与对照组MHR水平差异无统计学意义[12.3(8.1,16.0)vs11.9(8.5,16.0),P＞0.05].肿瘤组Syntax评分有高于对照组的趋势,但差异无统计学意义[12(7,23)vs10(5,18),P＞0.05].肿瘤组中Syntax≥23亚组和Syntax＜23亚组MHR水平差异无统计学意义,且MHR与Syntax积分无明显相关性(P＞0.05);对照组Syntax≥23亚组MHR水平高于Syntax＜23亚组[14.1(9.7～22.2)vs 11.6(8.5～15.5),P＜0.05],且 MHR 与 Syntax 积分呈正相关(r=0.210,P＜0.05).多因素 Logistic回归分析显示,MHR是对照组Syntax≥23的独立相关因素(OR=1.064,P＜0.05).结论 肿瘤组患者病变严重程度有高于对照组的趋势.不合并恶性肿瘤病史的冠心病患者MHR与Syntax积分呈正相关,MHR是Syntax≥23的独立相关因素;但在合并恶性肿瘤的冠心病患者中未发现这种相关性.

目的 探讨射血分数恢复型心力衰竭(HFrecEF)的早期临床特征.方法 对373例射血分数降低型心力衰竭患者行规范化治疗1年,观察射血分数未恢复组(HFrEF组)和HFrecEF组临床资料的区别.结果 HFrEF组男性比例、冠心病比例、年龄、吸烟、肌酐值及QRS时限均高于HFrecEF组(均P＜0.05),学历、收缩压、舒张压、高血压比例、瓣膜病比例、ACEI/ARB/ARNI使用率、单纯ARNI使用率、β受体阻滞剂使用率、肌钙蛋白-Ⅰ、血红蛋白、三酰甘油、LVEF均低于HFrecEF组(均P＜0.05).女性,高学历,窄QRS时限,应用ARNI治疗是LVEF是否恢复的独立预测因子(均P＜0.05).结论HFrecEF的早期临床特征主要包括年轻女性,不吸烟,正常肌酐值,窄QRS时限,相对较高的学历、血压、血红蛋白、初始LVEF值,应用ARNI药物治疗等.

Endothelial-mesenchymal transition (EndMT) is a differentiation process in which endothelial cells lose their own characteristics and acquire mesenchymal-like characteristics, which contributes to the formation and development of atherosclerotic plaques. Until now, there is still a lack of effective measures to treat atherosclerosis (AS), so there is an urgent need to understand the underlying mechanisms of AS. In addition, although various studies have shown that EndMT is involved in the pathological stages of cardiovascular diseases, such as myocardial fibrosis, myocardial hypertrophy, and hypertension, the specific molecular mechanisms driving EndMT are still in the exploratory stage. In this review, we review the role of histone modifications (methylation, demethylation and acetylation, deacetylation) on EndMT in cardiovascular disease, aiming to target histone-modifying enzymes to guide cardiovascular disease therapy.

目的 评估经导管主动脉瓣置换术(TAVR)治疗重度主动脉瓣狭窄的疗效.方法 35例重度主动脉瓣狭窄患者行TAVR治疗,分析手术即刻和术后1年的临床效果.结果 所有患者均成功置入自膨式瓣膜.35例患者主动脉瓣跨瓣压差均明显下降,术中经食道超声心动图验证无主动脉瓣狭窄,其中1例患者有瓣周瘘,即刻给予瓣中瓣治疗,术中球囊预扩张时采用双侧颈动脉按压保护,未出现脑梗死等并发症.与术前相比,患者1年后随访的主动脉瓣狭窄明显改善,平均跨瓣压差下降,氨基末端B型利钠肽前体下降,纽约心功能分级减少,明尼苏达生活质量评分下降,左室舒张末期内径缩小,左室射血分数和6min步行试验明显提高(均P＜0.05).结论 TAVR治疗高龄、重度主动脉瓣狭窄的疗效显著,可显著改善患者临床症状,但中远期效果有待进一步随访.

Inhibitor of differentiation 1 has a helix-loop-helix (HLH) structure, belongs to a class of molecules known as the HLH trans-acting factor family, and plays an important role in advancing the cell cycle, promoting cell proliferation and inhibiting cell differentiation. Recent studies have confirmed that inhibitor of differentiation 1 plays an important role in the endothelial-mesenchymal transition of vascular endothelial cells, angiogenesis, reendothelialization after injury, and the formation and rupture of atherosclerotic plaques. An in-depth understanding of the role of inhibitor of differentiation 1 in atherosclerosis will provide new ideas and strategies for the treatment of related diseases.

目的 探讨坎地沙坦改善血管紧张素Ⅱ导致的内皮损伤的机制.方法 (1)先用血管紧张素Ⅱ(AngⅡ)干预培养人脐静脉内皮细胞(HUVEC)构建氧化应激细胞株,再用氯沙坦或坎地沙坦对氧化应激的细胞株进行干预,最后用WB法检测eNOS、P-eNOS内皮功能蛋白,P38/P-P38、NF-KB/P-NF-KB炎症通路蛋白及血管紧张素转化酶2(ACE2)蛋白的表达情况.(2)先用AngⅡ和坎地沙坦干预HUVEC细胞构建模型细胞株,再用ACE2的小干扰RNA(siRNA)和ACE2激动剂(DIZE)干预模型细胞株,最后用WB法检测ACE2蛋白,P38/NF-KB通路中P-P38和P-NF-KB蛋白的表达情况.结果 (1)氯沙坦或坎地沙坦干预后,坎地沙坦组和氯沙坦组的P-eNOS蛋白较AngⅡ组的表达含量上升;坎地沙坦组和氯沙坦组P-P38及P-NF-KB的蛋白表达含量较AngⅡ干预组下降,且坎地沙坦组的下降趋势更加明显.(2)予DIZE干预后,HUVECs的ACE2蛋白表达升高,P-NF-KB蛋白的表达下降;予ACE2小干扰RNA干预后,HUVECs的ACE2表达下降;P-NF-KB蛋白的表达上升.结论 坎地沙坦除了可以通过拮抗AngⅡ的受体通路阻断P38/NF-KB炎症通路表达保护内皮细胞功能之外,还可以通过促进内皮细胞分泌ACE2抑制NF-KB炎症通路从而起到保护内皮细胞的作用.

Atherosclerosis, the pathophysiological basis of most malignant cardiovascular diseases, remains a global concern. Transcription factors play a key role in regulating cell function and disease progression in developmental signaling pathways involved in atherosclerosis. Activated transcription factor (ATF) 3 is an adaptive response gene in the ATF/cAMP response element binding (CREB) protein family that acts as a transcription suppressor or activator by forming homodimers or heterodimers with other ATF/CREB members. Appropriate ATF3 expression is vital for normal physiological cell function. Notably, ATF3 exhibits distinct roles in vascular endothelial cells, macrophages, and the liver, which will also be described in detail. This review provides a new perspective for atherosclerosis therapy by summarizing the mechanism of ATF3 in atherosclerosis, as well as the structure and pathophysiological properties of ATF3. KEY MESSAGES: • In endothelial cells, ATF3 overexpression aggravates oxidative stress and inflammation. • In macrophages and liver cells, ATF3 can act as a negative regulator of inflammation and promote cholesterol metabolism. • ATF3 can be used as a potential therapeutic factor in the treatment of atherosclerosis.