Abstract:Aortic aneurysm/dissection is the primary cause of mortality in patients with Marfan syndrome (MFS).Though aberrant activation of the transforming growth factor-β(TGF-β) pathway has been considered the central pathogenic mechanism for MFS aortic aneurysms, recent research has gradually revealed the involvement of other signaling pathways in MFS. This review summarizes the latest researches on the molecular mechanisms of MFS, including classical TGF-β and related signaling pathways such as Notch and nitric oxide(NO), as well as epigenetics and gene therapy, which provide new insights for the prevention and treatment of MFS.

Abstract:Aim To investigate the inhibition role and mechanism of adipose derived mesenchymal stem cell (ADMSC) exosomes (Exo) on adverse ventricular remodeling after myocardial infarction (MI). Methods The changes of autophagy and inflammasomes phenotype of cardiac fibroblasts after H₂O₂ treatment were observed. MI rats were injected with an equal volume of normal saline, adipose derived mesenchymal stem cell exosomes (MSC-Exo) or fibroblast exosomes (MEF-Exo) via a tail vein. The expression of autophagy related 16 like protein 1 (ATG16L1), autophagy related protein 7 (ATG7) and NOD-like receptor protein 3 (NLRP3), inflammatory response, the degree of myocardial fibrosis, and the cardiac function were observed in different groups. Results After treatment with H₂O₂ on cardiac fibroblasts, the expressions of ATG16L1 and ATG7 were significantly decreased (P＜0.001), NLRP3 was significantly increased (P＜0.001), and the levels of inflammatory cytokines interleukin-1β (IL-1β) and IL-18 were significantly elevated (P＜0.001). After MI rats were intervened with MSC-Exo, the expressions of autophagy related proteins ATG16L1 and ATG7 were significantly up-regulated (P＜0.001), NLRP3 was significantly down-regulated (P＜0.001), serum IL-1β and IL-18 levels were significantly decreased (P＜0.001), fibrosis-related proteins collagen Ⅰ and Ⅲ were significantly reduced (P＜0.001), myocardial fibrosis was significantly relieved (P＜0.001), and cardiac function was significantly improved (P＜0.001). Conclusion Adipose derived MSC-Exo play a role in inhibiting adverse ventricular remodeling after MI by regulating the balance of autophagy and NLRP3 inflammasomes.

Abstract:Aim To investigate whether SIRT6 overexpression inhibits angiotensin Ⅱ (AngⅡ)-induced cardiomyocyte apoptosis by activating adenosine 5′-monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase-1(AMPK/Nrf2/HO-1) signaling pathway. Methods The experiment was divided into 4 groups:control group,AngⅡ group,AngⅡ+SIRT6 group, AngⅡ+empty vector (EV) group. The mRNA level of SIRT6 was detected by RT-PCR. The cell activity was measured by MTT assay. The cell apoptosis was analyzed by flow cytometry. SIRT6, cardiomyocyte apoptosis related proteins (Bax, cleaved Caspase-3, Bcl-2), DNA damage related proteins (γ-H2AX, p-ATM), AMPK/Nrf2/HO-1 signaling pathway related proteins (p-AMPK, Nrf2, HO-1) were measured by Western blot. The reactive oxygen species (ROS) content was determined by DCFH-DA staining. The changes of the above indexes among the groups were observed. Results Compared with control group, the mRNA and protein expression levels of SIRT6 and cell activity were significantly decreased in AngⅡ group. Apoptosis rate, the expressions of Bax, cleaved Caspase-3 were increased, and the expression of Bcl-2 was decreased. The expressions of γ-H2AX and p-ATM were increased, and the expressions of p-AMPK, Nrf2, HO-1 were decreased. The activity of ROS was increased (P＜0.01). Compared with AngⅡ+EV group, the expression of SIRT6 and cell activity were significantly increased in AngⅡ+SIRT6 group. Apoptosis rate, the expressions of Bax and cleaved Caspase-3 were decreased, and the expression of Bcl-2 was increased. The expressions of γ-H2AX and p-ATM were decreased, the expressions of p-AMPK, Nrf2, HO-1 were increased. The activity of ROS was decreased (P＜0.01). Conclusion SIRT6 overexpression inhibits AngⅡ-induced cardiomyocyte apoptosis through activation of AMPK/Nrf2/HO-1 signaling pathway.

Abstract:Aim To explore the key genes in the blood transcriptome of atherosclerosis patients based on blood transcriptomics. Methods Three datasets GSE12288, GSE27034 and GSE90074 were extracted from the GEO database and performed the merging and normalization processing. The differential genes in peripheral blood samples of atherosclerosis patients and controls were analyzed, and enrichment analysis of differentially expressed genes were performed. Then weighted gene co-expression network analysis was performed for all genes. Using differentially expressed genes to construct protein-protein interaction (PPI) network, and using CytoHubba to screen key genes based on co-expression network and PPI network. And the expression levels of key genes were detected by RT-qPCR. Results 74 down-regulated genes and 145 up-regulated genes were identified between atherosclerosis patients and controls. GO and KEGG enrichment analyses revealed that they were significantly enriched in neutrophil activation, granulocyte activation, cytokine-cytokine receptor interaction and chemokine signaling pathway. In addition, the top 10 genes in the co-expression network and the top 20 genes in the PPI network were also identified, in which PRF1, NKG7, GZMB and CCL5 played a high core role in the PPI network and co-expression network. The RT-qPCR results showed that compared with the non coronary atherosclerosis controls, the mRNA expression levels of PRF1 and GZMB in peripheral venous blood peripheral blood mononuclear cell (PBMC) of coronary atherosclerosis patients were significantly reduced (P＜0.05), while the mRNA expression levels of NKG7 and CCL5 were significantly increased (P＜0.05). Conclusion PRF1, GZMB, NKG7 and CCL5 may be key genes in the blood transcriptome of atherosclerosis patients, and are expected to be potential biomarkers for diagnosis and treatment of atherosclerosis.

Abstract:Aim To investigate the levels of a disintegrin and metalloprotease 10 (ADAM-10) and soluble urokinase plasminogen activator receptor (suPAR) in the serum of hypertension patients with atherosclerosis and their relationship with the severity of disease. Methods From February 2021 to February 3,5 hypertension patients with atherosclerosis who visited our hospital were collected as the study group, and 76 healthy people were collected as control group. The patients in the study group were grouped into mild group (n＝40), moderate group (n＝42) and severe group (n＝43) according to the degree of atherosclerosis, after 60 days of treatment, the patients were grouped into a good prognosis group (n＝74) and a poor prognosis group (n＝51) based on their prognosis. Enzyme linked immunosorbent assay (ELISA) was applied to measure serum ADAM-10 and suPAR levels; Clinical data of patients with different prognosis were compared; Pearson method was applied to analyze the relationship between serum ADAM-10, suPAR levels and carotid intima-media thickness (IMT) in patients with hypertension and atherosclerosis; Multivariate Logistic regression was applied to analyze the influencing factors of poor prognosis in patients with hypertension and atherosclerosis; Receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of ADAM-10 and suPAR alone and jointly for poor prognosis of hypertension with atherosclerosis. Results The levels of serum ADAM-10 and suPAR were significantly higher in the study group than those in control group (P＜0.05); The serum ADAM-10 and suPAR levels in moderate group and severe group were obviously higher than those in mild group (P＜0.05), while the serum ADAM-10 and suPAR levels were obviously higher in severe group than those in moderate group (P＜0.05); The serum ADAM-10 and suPAR levels, left and right IMT, systolic blood pressure, and diastolic blood pressure of patients with poor prognosis were significantly higher than those of patients with good prognosis (P＜0.05); Pearson correlation analysis showed that serum ADAM-10 and suPAR levels in patients with hypertension and atherosclerosis were positively correlated with systolic blood pressure, diastolic blood pressure and IMT (P＜0.001); Logistic regression analysis showed that the increased levels of systolic blood pressure, diastolic blood pressure, ADAM-10, suPAR and IMT were risk factors for poor prognosis of hypertension patients with atherosclerosis (P＜0.05); ROC curve analysis showed that the area under the curve (AUC) of serum ADAM-10 and suPAR levels alone and jointly predicting poor prognosis of hypertension with atherosclerosis was 0.9,0.830 and 0.900, respectively, the combination of the two was superior to their individual predictions (Z_combination-ADAM-10＝2.766, P＝0.006; Z_combination-suPAR＝2.602, P＝0.009).Conclusion The levels of serum ADAM-10 and suPAR in patients with hypertension and atherosclerosis are significantly increased, and are positively correlated with the severity of atherosclerosis. Both of them have a high predictive value for evaluating the prognosis of patients with hypertension and atherosclerosis.

Abstract:Aim To explore the correlation between residual lipoprotein cholesterol (RLP-C) and the occurrence and severity of peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM). Methods 392 T2DM patients with complete data who attended the Department of Endocrinology and the Department of Cardiovascular Medicine of People's Hospital of Henan University of Traditional Chinese Medicine from May 2022 to December 2022 were selected and classified into PAD group (n＝203) and non-PAD group (n＝189). General clinical data were collected between the groups, the difference of RLP-C level was compared between the two groups, the correlation between RLP-C and PAD was examined by using univariate and multivariate Logistic regression analysis, and ROC curve was plotted to analyze the predictive value of RLP-C for PAD. Results Compared with non-PAD group, RLP-C level was significantly higher in PAD group (P＜0.001); RLP-C was positively correlated with the severity of PAD (r＝0.443, P＜0.001); Multifactorial Logistic regression analysis revealed that RLP-C was a major risk factor for the development of PAD in T2DM (P＜0.001); The area under the curve (AUC) of RLP-C level prediction for T2DM combined with PAD was 0.860 (95%CI: 0.824～0.896, P＜0.001); The optimal RLP-C threshold for predicting the development of PAD was 0.67 mmol/L. Conclusion RLP-C level was positively associated with the occurrence and severity of PAD in patients with T2DM, and RLP-C was an independent risk factor for the development of PAD. In addition, RLP-C＞0.67 mmol/L increased the risk of PAD in T2DM patients.

Abstract:Aim To explore the correlation between coronary artery calcification score (CACS) and retinal arteriosclerosis using artificial intelligence assisted analysis software. Methods 511 examinees who underwent physical examinations in the Department of Health Medicine of General Hospital of Eastern Theater Command in 2022 were selected as the research subjects, they were divided into a coronary artery calcification (CAC) group (＞0,1 cases) and a non CAC group (＝0,0 cases) based on the Agatston score, the clinical data of the two groups of examinees were compared using independent sample t-tests and chi square tests. According to the condition of retinal arteriosclerosis, the examinees were divided into three groups:normal retinal artery group, weakened retinal artery elasticity group and retinal arteriosclerosis group. Kruskal Wallis H test was used to compare the quantitative indicators of CACS and retinal microvasculature among the three groups; Spearman correlation analysis was used to study the correlation between CAC grading and clinical indicators, as well as quantitative indicators of retinal microvasculature; binary Logistic regression was used to analyze the correlation between retinal arteriosclerosis and CAC. Results The age, number of smokers, waist circumference, hip circumference, waist to hip ratio (WHR), body mass index (BMI), systolic blood pressure, serum creatinine (SCr), blood uric acid (BUA), blood urea nitrogen (BUN), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), triglyceride (TG) in the CAC group were higher than those in the non CAC group, and the difference was statistically significant (all P＜0.05). There were statistically significant differences in total CACS and AVR among the three groups of normal retina, weakened retinal artery elasticity and retinal arteriosclerosis (all P＜0.05), while there was no significant difference in CRAE and CRVE (all P＞0.05). The CACS level and total score were positively correlated with age, smoking status, waist circumference, hip circumference, WHR, BMI, systolic blood pressure, BUN, SCr, BUA, homocysteine (Hcy), FBG, 2 hour postprandial blood glucose (2h PBG), HbA1c, TG (all P＜0.05), and negatively correlated with gender, total cholesterol (TC), high density lipoprotein cholesterol (HDLC; all P＜0.05), but not with diastolic blood pressure and low density lipoprotein cholesterol (LDLC; all P＞0.05). The degree of retinal arteriosclerosis was positively correlated with age, waist circumference, hip circumference, WHR, BMI, systolic blood pressure, diastolic blood pressure, calcification scores of left main artery (LM), left anterior descending artery (LAD), left circumflex artery (LCX), right coronary artery (RCA), total CACS, BUN, FBG, 2h PBG, HbA1c and TG (all P＜0.05), and negatively correlated with TC, HDLC and LDLC (all P＜0.05), but not with gender, smoking status, pulse, SCr, BUA and Hcy (all P＞0.05). CAC level was negatively correlated with AVR (r＝－0.166, P＜0.05), and positively correlated with retinal arteriosclerosis level (r＝0.199, P＜0.05), but not significantly correlated with CRAE and CRVE (all P＞0.05). There was a correlation between CAC and retinal arteriosclerosis (P＜0.001). After adjusting for age, gender, smoking status, WHR, BMI, systolic blood pressure, FBG, SCr, BUA, BUN, and HDLC factors, the correlation between CAC and retinal arteriosclerosis still exists (P＝0.048). Conclusion AI assisted analysis of retinal vascular diameter and degree of retinal arteriosclerosis is related to CAC, which plays a positive role in risk assessment of atherosclerotic heart disease.

Abstract:Aim To investigate the effect of dipeptidyl peptidase-4 inhibitor (DPP-4i) on serum creatinine (Cr) in patients with type 2 diabetes mellitus (T2DM). Methods A systematic search was performed across databases of PubMed, Embase, Cochrane Library and Web of Science, and randomized controlled trials (RCT) of DPP-4i therapy for regulating Cr in T2DM patients was included. A fixed-effect or random-effect model was used for data fitting, heterogeneity was quantitatively evaluated according to the index of I², and sensitivity analysis and publication bias testing were performed by using the standard methods. Results After searching the database through the system, 12 RCTs were included, with a total of 2 276 participants. Due to the potential heterogeneity, a random effect model was used for data fitting. DPP-4i treatment could mildly increase Cr levels in T2DM patients (WMD:0.15 mg/L, 95%CI:0.03～0.27, I²＝18%, P＝0.02), and the results showed statistical differences. According to sensitivity testing, the results of Meta-analysis were relatively reliable. No publication bias was observed according to Begg’s and Egger’s tests. Conclusions The use of DPP-4i for hypoglycemic treatment in T2DM patients may result in mild elevation of blood Cr levels. Further multicenter studies with larger samples are needed in the future to explore the clinical significance of DPP-4i treatment induced changes in Cr levels.

Abstract:Acute myocardial infarction (AMI) is a severe disease caused by the persistent coronary artery obstruction, posing a great threat to people's health. In recent years, Toll-like receptor 4 (TLR4), an important pattern recognition receptor, has been widely studied and found to play a crucial role in AMI. This review introduces the recent progress of TLR4 in regulating the progression and prognosis of AMI, and summarizes recent TLR4-targeted therapies using clinical drugs, TLR4 inhibitors, mesenchymal stem cells, and natural bioactive molecules, providing valuable insights for addressing myocardial damage caused by AMI and improving prognosis.

Abstract:Atherosclerosis is a chronic vascular wall disease and the most common pathological change in cardiovascular disease. Its pathogenesis is closely related to inflammation, oxidative stress, and lipid deposition. Bilirubin itself has biological activities such as antioxidant and anti-inflammatory effects, and has a protective effect on the cardiovascular system. This article summarizes the mechanism of bilirubin in the development of atherosclerosis and its research progress.

Abstract:Atherosclerosis (As) is a chronic inflammatory disease associated with lipid deposition. Copper is considered to be an important trace element and is closely related to the occurrence and development of As. Excessive accumulation of copper ions in cells can induce cell death, a new type of cell death named “cuproptosis”. Under normal conditions, the body's copper metabolism can control the copper level in a stable range. When the disease occurs, copper homeostasis is destroyed, intracellular copper overload produces cytotoxicity, induces oxidative stress, inflammation, cell pyroptosis and cuproptosis, and promotes the occurrence and development of As. This article summarizes the relationship between copper levels and As, and discusses the mechanism of cuproptosis and the pathological mechanism of copper overload promoting As from the perspective of the body's copper regulation, and reviews the relevant drug intervention, expecting to provide a new therapeutic target for As.

Abstract:Atherosclerosis (As) is a chronic inflammatory disease caused by lipid deposition. Panvascular diseases, which are mainly caused by As, have gradually attracted the attention of many scholars, and their main pathological features are vascular lesions. Vitamin D plays an important role in anti-As in panvascular diseases. It is involved in the regulation of renin-angiotensin system (RAS), endothelial cell injury, immune response, neutrophil extracellular traps (NET) regulation, apoptosis and autophagy, and is a new target in panvascular diseases research. Traditional Chinese Medicine (TCM) has certain advantages in the prevention and treatment of panvascular diseases. Among them, single herbs, active ingredients and compound prescriptions can regulate vitamin D-related metabolism, and have unique scientific value for the prevention and treatment of As. This article mainly discusses the role of vitamin D in multiple pathological links of panvascular diseases and related Chinese medicine interventions, aiming to provide effective ideas for the prevention and treatment of panvascular diseases from the perspective of vitamin D.