Abstract:In recent years, the use of cell membrane-coated nanoparticles to develop biomimetic nanomedicines for atherosclerosis treatment has become a research hotspot. Among various cell membranes, due to the unique biological properties, red blood cells have been widely used as drug delivery. Erythrocyte membrane camouflaged biomimetic nanomedicines can not only prolong the circulation time and improve the biocompatibility in vivo, but also exhibit excellent passive targets through the enhanced permeability and retention effects of lesions for safe and efficient atherosclerosis therapy.Herein, this paper reviews erythrocyte membrane coating technology in the application of constructing the biomimetic nanomediciens in recent years, and focuses on its research applications in atherosclerosis therapy.

Abstract:Piezo1 protein is a non-selective mechanically gated cation channel. Under the action of mechanical stimulation, it can cause the influx of cations such as calcium, sodium, potassium, etc., and then convert the mechanical signals into bioelectrical signals, and integrate the signals into cells to participate in a variety of physiological and pathological processes. Piezo1 protein widely exists in the cardiovascular system, and plays an important role in many cardiovascular activities, such as blood flow shear stress and vascular tension sensing, vascular development and angiogenesis, and vascular remodeling. Piezo1 can sense the changes of blood flow shear stress and vascular tension, and its expression is also affected by them, thus affecting the morphology, arrangement, synthesis, secretion, inflammation and adhesion of vascular endothelial cells. Piezo1 can also regulate the migration, inflammatory reaction and lipid phagocytosis of macrophages, and participate in regulating the occurrence and development of atherosclerosis. The proliferation of vascular smooth muscle cells is also regulated by Piezo1, which then affects the remodeling of vascular wall. This article mainly reviews the discovery, structure and function of Piezo1 channel, and its research progress in atherosclerosis, in order to provide new ideas for the prevention and treatment of atherosclerosis.

Abstract:Aim To investigate the protective effect and mechanism of salvianolic acid B (SalB) on oxidized low density lipoprotein (ox-LDL)-induced foam cell formation in atherosclerosis. Methods Bone marrow-derived macrophages (BMDM) were extracted from mice, and cells were induced with 50 mg/L ox-LDL. The Piezo1 channel agonist Yoda1 was added to observe the correlation with Piezo1. The drug group was treated with different concentrations of SalB. Results Foam cell formation was significantly increased in Yoda1+ox-LDL group(P＜0.05). Compared with Yoda1+ox-LDL group, foam cell formation was significantly inhibited in SalB group (P＜0.05). Compared with normal control group, the protein expressions of inflammatory factors were increased in ox-LDL group, and they were more obvious in Yoda1+ox-LDL group. The protein expression levels of inflammatory factors were significantly decreased in SalB group(P＜0.05). In addition, the translocation of YAP protein into the nucleus was obvious in ox-LDL group, while it was more obvious in Yoda1+ox-LDL group, and the difference was significant (P＜0.05). The translocation of YAP protein into the nucleus was significantly reduced in SalB group. The expressions of phosphorylated P38, ERK1/2 and JNK proteins were increased in ox-LDL group and Yoda1+ox-LDL group, while they were significantly decreased in SalB group, and the difference was statistically significant (P＜0.05). Conclusion SalB inhibits foam cell formation and the protein expression levels of inflammatory factors induced by ox-LDL and Yoda1, thereby delaying the formation of atherosclerotic plaques. The mechanism may be that salvianolic acid B mediate Piezo1 to regulate MAPK/YAP axis.

Abstract:Cardiac fibrosis can cause cardiac diastolic and systolic disorders, induce arrhythmias, and increase the risk of hospital readmission and death in patients with cardiovascular disease. Fibroblasts are the main cell type that maintains and promotes extracellular matrix deposition in cardiac tissue and are sensitive to changes in the mechanical microenvironment. Recent studies have revealed the specific mechanical signal transduction pathways through which mechanical factors influence fibroblast function. In this review, mechanotransduction, vitro mechanical models and clinical advances are discussed.

Abstract:Mechanical force signals play an important role in the regulation of some cardiovascular diseases. Mechanical stress can be divided into tensile stress and shear stress. Tensile stress can affect all types of cells in blood vessels, while shear stress mainly affects endothelial cells, which cause changes in intracellular chemical signals through the action of mechanosensors, thereby regulating various life activities. Shear stress can regulate the occurrence of atherosclerosis and coronary heart disease by regulating inflammation-related signaling pathways; Various mechanical stresses can regulate the proliferation of vascular endothelial cells and smooth muscle cells, and induce fibrosis of the extracellular matrix, thereby increasing blood pressure and regulating occurrence of pulmonary arterial hypertension, and regulate the occurrence of cardiac hypertrophy by regulating MAPK, JAK/STAT and other signaling pathways. This review explores the relationship between mechanical force signals and the occurrence and development of some cardiovascular diseases, and expounds the molecular mechanism of mechanical force signals inducing some cardiovascular diseases, thus deepening our understanding of the occurrence and development of some cardiovascular diseases and providing some clues for their treatment.

Abstract:Aim To investigate the role of myeloid angiotensin type 1 receptor (Mye AT1R) in vascular insulin resistance and vascular injury in deoxycorticosterone acetate (DOCA)/salt-sensitive hypertensive mice. Methods C57BL/6J mice (wild type, WT) and Mye AT1R－/－ mice were randomly divided into WT group, DOCA/salt-sensitive hypertension group (DOCA group), Mye AT1R－/－group and Mye AT1R－/－/DOCA group, 8 in each group. DOCA/salt-sensitive hypertension was induced by left nephrectomy and DOCA sustained-release tablet implantation. Systolic blood pressure (SBP) was measured by tail cuff method. HE staining was used to observe aortic wall thickness, immunofluorescence was used to detect F4/80 (monocyte/macrophage marker) of aorta, RT-PCR and Western blot were used for mRNA and protein expressions of AT1R, proinflammatory factors and insulin signaling molecules. Acetylcholine or insulin-induced endothelium-dependent vasodilation was determined by isolated vascular perfusion system. Results Compared with WT group, in DOCA group, systolic blood pressure increased by 37%, aortic wall thickness increased by 57%, acetylcholine or insulin-induced endothelium-dependent vasodilation decreased by 32% and 36% respectively (P＜0.05), the number of F4/80 positive cells increased by 195%, the protein expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and phosphorylated c-Jun N-terminal kinase (p-JNK) were significantly increased by 42%, 45% and 32% respectively, the protein expression of p-Akt and p-Enos decreased by 36% in the aorta of DOCA mice (P＜0.05). Specific knockout of myeloid AT1R, aortic thickness decreased by 14%, the number of F4/80 positive cells decreased by 44%, acetylcholine or insulin-induced endothelium-dependent vasodilation improved by 21% and 17% respectively, the protein expression of MCP-1, TNF-α and p-JNK decreased by 52%, 41% and 17% respectively, damaged insulin protein PI3K/Akt/eNOS signaling pathway was reversed, the protein expression of p-Akt and p-eNOS increased by 48% and 42% respectively (P＜0.05) without significant reduction in systolic blood pressure. Conclusion Knockout of Mye AT1R can reduce vascular insulin resistance and vascular injury caused by salt-sensitive hypertension, and its mechanism may be related to inhibition of vascular inflammation caused by macrophage infiltration in vascular wall.

Abstract:Aim To investigate the correlation between erythropoietin-producing hepatocellular receptor A2 (EphA2), progranulin (PGRN), and endothelial inflammatory and adhesion factors in patients with coronary artery disease (CAD). Methods From January to December 0,3 CAD patients who were admitted to the Department of Cardiology of Zhongshan Hospital Affiliated to Fudan University for coronary angiography were selected. 5 mL of elbow vein blood was collected on an empty stomach the next morning after admission. Serum EphA2 and PGRN levels were determined by ELISA, and serum tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1) and interferon-γ (IFN-γ) levels were determined by Premixed Luminex. Results The levels of serum EphA2, N-terminal pro-brain natriuretic peptide (NT proBNP), cardiac troponin T (cTnT), high sensitivity C-reactive protein (hs-CRP), creatine kinase isoenzyme-MB (CK-MB) myocardial injury markers in patients with acute coronary syndrome (ACS) were 6.3 times, 15 times, 161 times, 13 times, 2.5 times higher than those in patients with chronic coronary syndrome (CCS) (P＜0.001), and serum TNF-α, IL-6 and VCAM-1 were 37.9%, 500.0% and 196.6% higher than those in CCS patients (P＜0.01), and serum PGRN levels were not significantly higher than those in CCS patients (P＝0.051). The area under curve (AUC) of serum EphA2, PGRN, IL-6, and VCAM-1 in predicting ACS were 0.2,0.6,0.926 and 0.861 respectively. Serum EphA2, VCAM-1, IL-6, TNF-α and MCP-1 was positively correlated with Gensini scores (r＝0.533, P＜0.001; r＝0.549, P＜0.001; r＝0.621, P＜0.001; r＝0.263, P＝0.027; r＝0.264, P＝0.026). Serum EphA2 was positively correlated with IL-6 and VCAM-1 respectively (r＝0.565, P＜0.001; r＝0.474, P＜0.001). There was no correlation between PGRN and inflammatory factors and adhesion factors (P＞0.05). Serum PGRN and EphA2 were positively correlated with myocardial injury markers (P＜0.05). Conclusions This study supports that EphA2 is involved in the process of endothelial inflammation in the acute stage of plaque injury from a clinical perspective, and suggests that EphA2 and PGRN may be potential targets to intervene in endothelial inflammation and predict the progression of atherosclerotic lesions.

Abstract:Aim To investigate the relationship between serum signal peptide-CUB-epidermal growth factor domain containing protein 1 (SCUBE1), endothelial cell specific molecule-1 (Endocan) levels and no coronary reflow after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (ASTEMI). Methods 120 ASTEMI patients treated by emergency PCI in the Emergency Department of Sanya People's Hospital of Hainan Province were included in observation group. According to the blood flow classification of thrombolysis in myocardial infarction (TIMI) after PCI, ASTEMI patients were divided into no-reflow group and reperfusion group. Another 60 healthy subjects were selected into control group. Blood samples were collected to measure and compare the levels of serum SCUBE1 and Endocan in patients with ASTEMI before PCI, immediately after PCI, 48 hours after PCI and in control group. Multivariate Logistic regression was used to analyze the risk factors of no-reflow. ROC curve was used to analyze the clinical value of SCUBE1 and Endocan before PCI in predicting no-reflow of coronary artery after PCI. Results Compared with control group, the levels of serum SCUBE1 and Endocan in observation group were increased before PCI, immediately after PCI and 48 hours after PCI (P＜0.05). There were significant differences in left ventricular ejection fraction, proportion of history of coronary heart disease, C-reactive protein, neutrophil/lymphocyte, troponin T, time from onset to reperfusion and lesion length between no-reflow group and reperfusion group (P＜0.05). Compared with the reperfusion group, the levels of serum SCUBE1 and Endocan in no-reflow group were increased before PCI, immediately after PCI and 48 hours after PCI (P＜0.05). Multivariate Logistic regression analysis showed that the history of coronary heart disease, left ventricular ejection fraction, SCUBE1 and Endocan levels before PCI were significant factors affecting the occurrence of no-reflow of coronary artery after PCI (P＜0.05). The area under the ROC curve predicted by SCUBE1 combined with Endocan before PCI was 0.870 (95%CI:0.785～0.955). Conclusion The high serum levels of SCUBE1 and Endocan before PCI are risk factors affecting no-reflow of coronary artery after PCI in patients with ASTEMI.The combined detection of SCUBE1 and Endocan before PCI is helpful to predict the risk of no-reflow of coronary artery after PCI.

Abstract:Aim To investigate the predictive value of pulse pressure index (PPI) combined with arteriosclerosis index (AI) on coronary artery disease severity in patients with coronary heart disease (CHD). Methods A total of 150 patients who were diagnosed with CHD after coronary angiography (CAG) in Foshan Hospital of Traditional Chinese Medicine from January 2019 to October 2019 were selected and grouped into single-branch group (36 cases), double-branch group (49 cases), and three-branch group (65 cases); fifty patients without CHD after CAG recurrently were included in the control group. CHD classification:37 cases in stable angina pectoris (SAP) group, 42 cases in unstable angina pectoris (UAP) group, 35 cases in non-ST segment elevation myocardial infarction (NSTEMI) group, ST segment elevation myocardial infarction (STEMI) group of 36 cases. The differences in PPI and AI levels among each groups were compared, and the influencing factors of coronary artery disease severity in CHD patients were analyzed. The correlation between Gensini score and PPI and AI level was analyzed by Pearson analysis. The efficacy of PPI and AI in predicting coronary artery disease severity was analyzed by ROC curve. Results The levels of PPI and AI in the single-branch group, double-branch group, and three-branch group increased sequentially (P＜0.05). Compared with the SAP group, UAP group, NSTEMI group and STEMI group, there was no significant difference in PPI and AI levels (P＞0.05). Both PPI and AI were positively correlated with Gensini score (r＝0.561, r＝0.629, both P＝0.000). Multivariate Logistic regression showed that PPI and AI were the risk factors for CHD, and PPI, AI and Gensini score were the influencing factors of three-branch coronary artery disease (P＜0.05). The area under curve (AUC) of PPI and AI to predict CHD was 0.809 and 0.899, respectively, and the AUC of PPI combined with AI to predict CHD was 0.937. The AUC of PPI and AI for predicting three-branch coronary artery disease was 0.893 and 0.917, respectively, the PPI combined with AI had higher efficacy in predicting three-branch coronary artery disease, with an AUC of 0.969. Conclusion PPI and AI are closely related to severity of coronary artery disease in CHD patients. PPI combined with AI has high predictive value for coronary artery disease severity in CHD patients.

Abstract:Atherosclerosis (As) is the pathological basis of coronary heart disease, and vascular endothelial injury is the initiating factor of coronary atherosclerosis. Vascular endothelial cells are a single layer of cells located in the inner layer of blood vessels and regulates exchanges between the blood stream and the surrounding tissues, and their integrity is very important. Many active monomers and the derivatives in natural products of traditional Chinese medicine modulate the function of endothelial cells by intervening oxidative stress, regulating the release of vasoactive substances, reducing inflammation, and equilibrating coagulation and anticoagulant system. They have the advantages of multi-pathway, multi-link and multi-target regulation in protecting from endothelial injury and attenuating atherogenesis. They have also been used to protect against corona virus disease 2019 (COVID-19) induced endothelial injury and atheroslerosis. This article reviews the research progress of the above issues in this field.

Abstract:Atherosclerosis (As), as a chronic arterial wall inflammatory response in panvascular diseases, is one of the main causes of cardiovascular and cerebrovascular diseases. At present, more and more studies have shown that circular RNA (circRNA) are involved in the pathogenetic process of atherosclerosis formation and development. It can mediate microRNA (miRNA) regulation of messenger RNA (mRNA) expression in target genes. The mechanisms include endothelial cells, vascular smooth muscle cells and macrophages proliferation, migration, differentiation, apoptosis and inflammation and other processes. And it involves multiple complex signaling pathways. In this review, we comprehensively analyze the biological function of circRNA/miRNA/mRNA and its effect on As in order to provide new ideas for the diagnosis and treatment of atherosclerotic diseases.

Abstract:Coronary artery calcification is commonly seen in patients with coronary atherosclerotic heart disease, but the mechanism of its happening, development, and formation is less known. Gla-rich protein (GRP) is a newly discovered vitamin K-dependent protein. Studies have shown that GRP inhibits the formation and maturation of calcified crystals by binding to minerals, participates in the inhibition pathway of matrix Gla protein-fetuin-A calcification, blocks the signalling pathway of calcification inducers and has an anti-inflammatory effect, thus playing a role in inhibiting vascular calcification. In this paper, the research progress of GRP's participation in the mechanism of coronary artery calcification will be conducted in the hope of providing a new direction for the prevention and treatment of coronary artery calcification.