Abstract:Angiogenesis within atherosclerotic plaques is a critical determinant of plaque stability. The biomechanical microenvironment, consisting of fluid shear force, plaque structural stress, and matrix stiffness, serves as significant factors in mediating plaque angiogenesis. Endothelial cells respond to mechanical signals and participate in plaques neovascularization through force chemical signal transduction mechanisms. This review provides an overview of the mechanisms by which mechanical factors regulate angiogenesis within plaques and offers a novel therapeutic approach for the prevention and treatment of atherosclerosis.

Abstract:Aim The key genes for necroptosis in atherosclerosis were screened by bioinformatics methods and verified with the help of in vitro experiments to provide new strategies for the prevention and treatment of atherosclerosis from the perspective of necroptosis. Methods Genes related to atherosclerotic plaques were downloaded from GEO database, and genes related to necroptosis were downloaded from GeneCards database and intersected to obtain atherosclerotic necroptosis genes, and the mechanism of action and signalling pathways of the genes were further analysed by GO and KEGG enrichment analysis, and the protein-protein interaction (PPI) network was constructed and screened for key genes.Finally, macrophages were treated with oxidized low density lipoprotein (ox-LDL) at a final concentration of 100 mg/L, and the expression of key genes was detected by RT-PCR and Western blot. Results A total of 81 atherosclerotic necroptosis genes were obtained. GO and KEGG enrichment analyses revealed that they were mainly enriched in the positive regulation of endopeptidase activity, IκB kinase (IKK)/nuclear factor-κB (NF-κB) signalling, and autophagy signalling pathway. Five key genes including HSPA8, STAT3, HMOX1, SQSTM1 and FAS were obtained by using five computational methods of Cytoscape software cytoHubba plug-in. Compared with the normal control group, the HMOX1 gene was highly expressed in THP-1 macrophages treated with ox-LDL (P＜0.05), while the expression of the HSPA8, STAT3, SQSTM1 and FAS genes showed no significant changes (P＞0.05); the HMOX1 and SQSTM1 genes were highly expressed in RAW264.7 macrophages treated with ox-LDL (P＜0.05), while HSPA8, STAT3 and FAS genes showed no significant changes (P＞0.05). The expression of HMOX1 protein in THP-1 macrophages was also increased. Conclusion HMOX1 may be the key gene of atherosclerotic necroptosis, and it is expected to become a new target for the prevention and treatment of atherosclerosis.

Abstract:Aim To explore the mechanism of oxiracetam promoting neurogenesis and migration in rats with cerebral infarction through stromal cell-derived factor-1α (SDF-1α)/C-X-C chemokine receptor 4 (CXCR4) pathway. Methods 100 SD rats were randomly divided into control group, cerebral ischemia (CI) group, oxiracetam (200 mg/kg) group, and oxiracetam (200 mg/kg)＋AMD3100 (5 mg/kg) group, with 25 rats in each group. Electrocoagulation was used to create rat model of local permanent cerebral infarction. After 1,7 and 14 days of modeling, neurological deficits were scored, TTC staining was used to detect the volume of cerebral infarction, Nissl staining was used to detect cell survival in the infarcted area, Western blot was used to detect SDF-1α and CXCR4 protein levels in ischemic zone. After 1～7 days of modeling, BrdU (50 mg/kg) was continuously injected intraperitoneally. After 14 days, immunofluorescence double staining was used to detect the number of BrdU＋Nestin＋and BrdU＋DCX＋ cells in the SVZ region. 5 days before modeling, retroviruses carrying GFP were injected into the SVZ region. After 14 days, immunofluorescence double staining was used to detect the number of GFP＋DCX＋, GFP＋MAP-2＋ and GFP＋GFAP＋ cells in infarction area. C17.2 cells were divided into control group, oxygen-glucose deprivation (OGD) group, oxiracetam (final concentration:200 mg/L) group, and oxiracetam (final concentration:200 mg/L)＋AMD3100 (final concentration:100 μmol/L) group. OGD was used to create cell CI model. After 12 hours, immunofluorescence double staining was used to detect the number of BrdU＋/Nestin＋ and BrdU＋/MAP-2＋ cells, Transwell experiment was used to detect cell migration, Western blot was used to detect SDF-1α and CXCR4 protein levels in cell culture supernatant. Results Animal experiment results showed:compared with control group, mNSS score in CI group was increased, cerebral infarction volume was increased, the number of surviving cells in infarcted area was decreased, SDF-1α and CXCR4 protein levels were increased, the number of GFP＋DCX＋, GFP＋MAP-2＋ and GFP＋GFAP＋ cells in SVZ region were increased (P＜0.05); compared with CI group, mNSS score in oxiracetam group was decreased, cerebral infarction volume was decreased, the number of surviving cells in infarcted area was increased, SDF-1α and CXCR4 protein levels were increased, the number of GFP＋DCX＋, GFP＋MAP-2＋ and GFP＋GFAP＋ cells in SVZ region were increased, the number of GFP＋DCX＋, GFP＋MAP-2＋ and GFP＋GFAP＋ cells in infarcted area were increased (P＜0.05); compared with oxiracetam group, mNSS score in oxiracetam＋AMD3100 group was increased, cerebral infarction volume was increased, the number of surviving cells in infarcted area was decreased, CXCR4 protein level was decreased, the number of GFP＋DCX＋, GFP＋MAP-2＋ and GFP＋GFAP＋ cells in the SVZ region were decreased (P＜0.05). Cell experiment results showed:compared with control group, the number of BrdU＋/Nestin＋ and BrdU＋/MAP-2＋cells in OGD group were increased, the number of cell migration, SDF-1α and CXCR4 protein levels in cell culture supernatant were increased (P＜0.05); compared with OGD group, the number of BrdU＋/Nestin＋ and BrdU＋/MAP-2＋cells in oxiracetam group were increased, the number of cell migration, SDF-1α and CXCR4 protein levels in cell culture supernatant were increased (P＜0.05); compared with oxiracetam group, the number of BrdU＋/Nestin＋ and BrdU＋/MAP-2＋cells in oxiracetam＋AMD3100 group were decreased, the number of cell migration, CXCR4 protein level in cell culture supernatant were decreased (P＜0.05). Conclusion Oxiracetam may promote the migration of neural stem cells from the SVZ region to the ischemic zone, promoting neurogenesis and functional recovery in rats with cerebral infarction by activating SDF-1α/CXCR4 pathway.

Abstract:Myocardial infarction is myocardial necrosis caused by acute and persistent ischemia and hypoxia of coronary artery, with high incidence rate and mortality. Although the recovery of blood supply through coronary intervention or thrombolytic drugs can improve the survival rate of patients, it is difficult to rescue the lost cardiomyocytes in the infarcted area, and the limited self repair ability of the adult mammalian heart is the main factor that causes myocardial fibrosis and eventually progresses to heart failure. For a long time, the existing treatment methods are difficult to reverse the process of heart failure after myocardial infarction. Cell transplantation is a promising therapeutic method to promote the repair and regeneration of infarcts. Due to the ischemia and hypoxia microenvironment, the limited survival and retention of stem cells after transplantation are not ideal. And acellular biomaterials promoting angiogenesis and reducing fibrosis show the potential of preclinical treatment. This paper summarizes the advantages and disadvantages of various acellular biomaterials, epicardial infarct repair and intramyocardial injection in a minimally invasive manner to promote cardiac regeneration and improve cardiac function, and to promote myocardial regeneration by combining acellular biomaterials with optimized drugs in the future for reference.

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:Acute aortic dissection (AAD) is a very dangerous cardiovascular emergency. Although some progress has been made in diagnosis and treatment, the mortality rate of AAD is still high. AAD is a multi-factor involved disease, and its pathophysiological mechanism has not been fully explained, so its clinical treatment effect is limited and its mortality rate is extremely high. A large number of studies have shown that serum amyloid A (SAA), as a major inflammatory protein produced in the acute phase response, is closely related to the occurrence and development of cardiovascular diseases.Therefore, SAA may become a candidate target for the diagnosis and treatment of AAD. This review discusses the relationship between SAA and inflammatory response, vascular dysfunction, thrombosis and extracellular matrix remodeling, and the possibility of SAA as a potential biomarker of AAD.

Abstract:Aim GEO database was used to explore the common pathogenesis of gout complicated with atherosclerosis (As). Methods The gene expression matrices of gout (GSE160170) and As (GSE100927) were downloaded from the GEO database, the differentially expressed genes (DEG) of gout and As were analyzed, and enrichment analysis was performed separately. After analyzing the common differentially expressed genes (CDEG), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and hub genes (HG) identification were performed on them, and co-expression analysis and validation were performed on hub genes. Finally, the immune cell infiltration of gout and As was analyzed, and the correlation between hub genes and infiltrating immune cells (IIC) was explored. Results The GSE160170 dataset obtained 1 606 differentially expressed genes, while the GSE100927 dataset obtained 481 differentially expressed genes. The enrichment analysis of 22 differentially expressed genes showed that the regulation of cytokines may be the key mechanism of gout complicated with As. Six hub genes (CCR2, CD2, FCGR3A, FGD3, IL10RA, SIGLEC1) were identified using the CytoHubba plugin, and the validation results of these hub genes showed that they were still reliable. The co-expression network showed that these hub genes could affect the regulation of tumor necrosis factor superfamily cytokines. Immune cell infiltration analysis showed that the expression of NK cells in gout was significantly increased, and was significantly related to CCR2 gene. The expression of living fertilizer large cells in As was significantly increased, and was significantly related to CD2 gene. Conclusion The regulatory effect of tumor necrosis factor superfamily cytokines may be the core factor of gout complicated with As.

Abstract:Atherosclerosis is the leading cause of cardiovascular and cerebrovascular diseases caused by smoking, hypertension, aging, obesity, circadian clock disorders, and other factors. As a molecular machine for protein synthesis, ribosomes maintain protein homeostasis in cells. This review focuses on the impact of aging, obesity, and circadian clock disorders on the development of atherosclerosis and the relationship with ribosome biogenesis and provides the theoretical basis for both basic research and clinical intervention of atherosclerosis.

Abstract:Aim Through the exoRBase database to screen the differentially expressed exosomal genes and build the CeRNA network in the peripheral blood of coronary heart disease (CHD), and then explore the key genes and regulatory mechanisms leading to the onset and progression of CHD. Through the key genes of differentially expressed mRNA who were enriched by GO and KEGG analysis, to study the molecular function and biological processes of the differentially expressed mRNA in CHD. Methods The R language was used to screen the differentially expressed exosomal genes in the peripheral blood of CHD, and the online databases and Cytoscape software was used to construct the CeRNA networks.And then visualized and analyzed the key genes. In the end, the GO and KEGG enrichment analysis was performed for the differentially expressed mRNA key genes. Results A total of 312 exosomal mRNA, 43 exosomal lncRNA and 85 exosomal circRNA with differential expressed were screened out from the peripheral blood of CHD patients. Through the construction of the CeRNA network, it was found that mRNA, lncRNA and circRNA competitively bound to miRNA, and the expressions of lncRNA combined with miRNA were significantly up-regulated, while the expressions of mRNA and circRNA were mostly significantly down-regulated. The GO and KEGG enrichment analysis of key genes of differentially expressed mRNA showed that these key genes were mainly related to “phosphatase activator activity” and “phosphatase regulatory activity” functions. Conclusions The peripheral blood exosomes screened by exoRBase database in patients with CHD are significantly different from those in healthy people, and mRNA, lncRNA and circRNA can competitively combine with miRNA significantly related to CHD and achieve mutual regulation. These genes may be involved in the occurrence and development of CHD and can be used as its regulatory points and therapeutic drug targets.

Abstract:Mitochondria are important organelles in mammalian cells. As the regulatory center of cell energy metabolism and cell death, mitochondrial dysfunction will lead to the occurrence and development of a variety of diseases. Mitochondrial function depends on the integrity and homeostasis of mitochondrial proteome. Therefore, mitochondrial protein quality control system is very important to maintain mitochondrial homeostasis and body health. When mitochondria and their protein quality control system are abnormal, it will directly damage mitochondria and lead to abnormal mitochondrial protein accumulation, resulting in intracellular environmental disorder and even cell dysfunction, which may affect the occurrence and development of atherosclerotic diseases. This paper reviews the role of mitochondria and its protein quality control system in the occurrence and development of atherosclerotic diseases, and looks forward to the future development prospects and challenges in this field, in order to providing scientific evidence for finding specific mitochondrial protein closely related to atherosclerotic diseases.