Abstract:At present, with the development of new diagnostic technologies, the detection rate of aortic dissection has been increasing year by year, but its mortality rate still remains high. Cardiovascular disease is a chronic inflammatory disease, and vascular inflammation plays a major role in the progression of aortic dissection. Therefore, this article systematically describes the specific roles and mechanisms of inflammatory cells, inflammatory factors, and inflammasomes in the development of aortic dissection.

Abstract:Aim To explore the effect of Buyang Huanwu decoction on anti-atherosclerosis by regulating the phenotypic transformation of vascular smooth muscle cells and serum inflammatory response based on Wnt/β-catenin signaling pathway. Methods 50 ApoE－/－ mice were randomly divided into model group, Buyang Huanwu decoction modified (low, medium and high dose) groups, and atorvastatin group, with 10 mice in each group; 10 C57BL/6J mice with the same genetic background were set as the control group. The mice of control group were fed with regular forages, while the mice of other five groups were fed with high-fat forages for 8 weeks for model replication. From the 9th week, they were continuously gavaged for 4 weeks. After 12 weeks, the mouse aortic roots were isolated and paraffin sections were prepared. Oil red O staining was used to observe the lipid content of aortic sinus. Immunohistochemical method was used to detect the expression level of bone bridge protein (OPN). Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) in serum. Western blot was used to detect the protein expressions of Wnt1, β-catenin and c-myc in mice aorta. RT-PCR was used to detect the expressions of Wnt1 and β-catenin gene. Results Buyang Huanwu decoction modified (low, medium and high dose) could reduce the lipid content and OPN expression in the aortic sinus of As model mice, reduce serum levels of IL-6 and TNF-α, IL-1β and MCP-1 in mice, and downregulate the expression of Wnt1 and β-catenin protein and gene. Conclusion Buyang Huanwu decoction modified exerts an anti-atherosclerosis effect by regulating inflammatory response, and some of the mechanisms may be related to inhibiting the activation of the Wnt/β-catenin signaling pathway.

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:Aortic dissection refers to the dissection hematoma formed when the intima of the aorta is torn by itself or external factors, and the blood in the lumen enters the middle layer of the artery wall through the intima breach. Aortic dissection is a dangerous acute disease and if the aortic dissection is completely torn, it will quickly lose blood and lead to circulatory failure and immediate death. Nonetheless, mechanistic studies of aortic dissection are currently poorly understood. Non-coding RNA is an independent RNA transcript, accounting for more than 90% of human genomic RNA. It usually does not encode protein, but acts as an important regulator to maintain normal physiological functions. So far, many studies have demonstrated that non-coding RNA are involved in the regulation of cardiovascular diseases. Therefore, much attention has been paid to the study of non-coding RNA in aortic dissection. This article reviews the mechanism of non-coding RNA in aortic dissection, and emphasizes that non-coding RNA is a biomarker of aortic dissection and a potential preventive and therapeutic means to target aortic dissection, providing a broad idea for the development of targeted drugs using non-coding RNA as a carrier in the future.

Abstract:Acute coronary syndrome (ACS) is a group of clinical syndromes with high morbidity and mortality worldwide. Increasing evidence suggest that plaque erosion with an intact fibrous cap is one of the major causes responsible for ACS. Basic experiments have shed light on the unique molecular characteristics of plaque erosion. It has been indicated that plaque erosion starts with the changes of blood flow disturbance-induced endothelial cell damage, resulting in loss of basement membrane integrity and endothelial cell desquamation, with consequent formation of neutrophil extracellular traps and thrombosis. This review will discuss the molecular characteristics of atherosclerotic plaque erosion and translational research needed for future precision medicine in patients with plaque erosion.

Abstract:Atherosclerosis is a chronic inflammatory disease characterized by lipid deposition in the arterial vessel wall, in which both innate and adaptive immune cells are involved in the disease process and play different roles. Metabolic reprogramming of these immune cells modulates disease progression by modulating immune cell phenotype and function. This article reviews the metabolic pathway changes of major immune cells associated with the course of atherosclerosis, and summarizes the types and mechanisms of metabolic reprogramming among these immune cells.

Abstract:Aim To investigate the influences of ginkgetin on the ferroptosis of vascular endothelial cells induced by oxidized low density lipoprotein (ox-LDL) by regulating the nuclear factor erythroid-2 related factor 2 (Nrf2)/solute carrier protein 7 family member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. Methods Human umbilical vein cell fusion cells EA.hy926 were grouped into normal control group (normal culture), ox-LDL group (50 mg/L ox-LDL), and ginkgetin low dose group (50 mg/L ox-LDL+10 μmol/L ginkgetin), middle dose group (50 mg/L ox-LDL+20 μmol/L ginkgetin), high dose group (50 mg/L ox-LDL+40 μmol/L ginkgetin), ML385 group (50 mg/L ox-LDL+40 μmol/L ginkgetin+1 μmol/L Nrf2 inhibitor ML385), Erastin group (50 mg/L ox-LDL+40 μmol/L ginkgetin+5 μmol/L SLC7A11 inhibitor Erastin), RSL3 group (50 mg/L ox-LDL+40 μmol/L ginkgetin+0.5 μmol/L GPX4 inhibitor RSL3). Cell viability was detected by tetramethylazolium salt (MTT) method. The kits were applied to detect the levels of cellular superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH). The intracellular iron content was detected by specific fluorescent probe method. The levels of intracellular reactive oxygen species (ROS) and lipid ROS were detected by 2′, 7′-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe method and boron dipyrrole (BODIPYTM) method; Western blot was applied to detect the protein expressions of cellular Nrf2, SLC7A11, GPX4,4-hydroxynonenoic acid (4-HNE), cyclooxygenase 2 (COX2), and p53. Results Compared with the normal control group, the cell viability, SOD content, GSH content, expressions of Nrf2, SLC7A11 and GPX4 were obviously decreased in the ox-LDL group (P＜0.05); the MDA content, Fe2＋ content, ROS, lipid ROS, expressions of 4-HNE, COX2, p53 were obviously increased (P＜0.05). Compared with the ox-LDL group, the cell viability, SOD content, GSH content, expressions of Nrf2, SLC7A11 and GPX4 were obviously increased in low, middle and high dose groups of ginkgetin (P＜0.05); the MDA content, Fe2＋ content, ROS, lipid ROS, expressions of 4-HNE, COX2, p53 were obviously decreased (P＜0.05). Compared with the high dose ginkgetin group, the ML385 group, Erastin group and RSL3 group attenuated the inhibitory effect of ginkgetin on ox-LDL-induced vascular endothelial cell ferroptosis. Conclusion Ginkgetin inhibits ox-LDL-induced vascular endothelial cell ferroptosis by activating the Nrf2/SLC7A11/GPX4 pathway.

Abstract:Aim To observe the effect of edaravone dexborneol (EDDE) on neuronal apoptosis in rats with cerebral ischemia-reperfusion, and to explore its mechanism. Methods SD rats were randomly divided into sham group, middle cerebral artery occlusion (MCAO) group, low-dose EDDE group (EDDE-L group, 3 mg/kg), and high-dose EDDE group (EDDE-H group, 6 mg/kg), chelerythrine (CHE, PKC inhibitor) group (5 mg/kg CHE), EDDE＋CHE group (6 mg/kg EDDE＋5 mg/kg CHE), with 15 rats in each group. Except for the sham group, the rats in the other groups were given the suture method to construct the MCAO model. The rats in each group were scored for neurological deficits; after 24 hours of reperfusion, TTC staining was used to detect the cerebral infarct volume of rats; HE staining was used to observe the pathological damage of cortical nerve cells; TUNEL staining was used to detect cortical nerve cells apoptosis; immunohistochemical method was used to detect the expression of Bcl-2 and Bax in the cortex nerve cells; Western blot was used to detect the expression of Caspase-3, cleaved Caspase-3 and protein kinase C (PKC)/extracellular signal-regulated kinase (ERK) pathway related proteins (PKC, p-PKC, ERK1/2 and p-ERK1/2) in brain tissue. ResultsCompared with sham group, the neurological deficit score, the percentage of cerebral infarction volume and the apoptosis rate of nerve cells increased, the positive expression of Bax increased and the ratio of cleaved Caspase-3/Caspase-3 increased (all P＜0.05), the positive expression of Bcl-2 decreased, the ratio of Bcl-2/Bax, p-PKC/PKC and p-ERK1/2/ERK1/2 decreased in brain tissue (all P＜0.05), the cerebral cortex cells were sparsely arranged, swelling and vacuolar degeneration of nerve cells were obvious, the nucleus shrank and the tissue becomes necrotic in MCAO group. Compared with MCAO group, the neurological deficit score, cerebral infarction volume percentage and apoptosis rate of nerve cells decreased, the positive expression of Bax decreased, the ratio of cleaved Caspase-3/Caspase-3 decreased (all P＜0.05), the positive expression of Bcl-2 increased, the ratio of Bcl-2/Bax, p-PKC/PKC and the ratio of p-ERK1/2/ERK1/2 increased in brain tissue (P＜0.05) in the EDDE-L group and EDDE-H group, the pathological damage of the cerebral cortex was improved to varying degrees, the number of nerve cells increased, the vacuolar degeneration was reduced, the nucleus was clearer, and the EDDE-H group was better than the EDDE-L group. CHE could eliminate the neuroprotective effect of EDDE. Conclusion EDDE cloud inhibit neuronal apoptosis and reduce cerebral ischemia/reperfusion injury, and its mechanism may be related to the activation of PKC/ERK pathway.

Abstract:Aim To explore the effect and molecular mechanism of procaine on hypoxia induced injury of N9 and PC12 cells. Methods N9 cells and PC12 cells were divided into control group, hypoxia group, low, medium and high dose (hypoxia＋2,6, 18 mg/L procaine) procaine group, anti-miR-con group, anti-miR-369-3p group, miR-con＋high dose procaine group (transfection miR-con＋hypoxia＋18 mg/L procaine), miR-369-3p＋high dose procaine group (transfection miR-369-3p＋hypoxia＋18 mg/L procaine). Flow cytometry was used to detect apoptosis, reagent kit was used to detect the content of reactive oxygen species (ROS) and malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), ELISA was used to detect the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). RT-qPCR was used to detect the expression of miR-369-3p. Results Compared with the control group, the apoptosis rate of N9 cells and PC12 cells in the hypoxia group increased, the content of MDA and ROS increased, the activity of SOD decreased, the levels of TNF-α, IL-1β and IL-6 increased, the expression of miR-369-3p increased (P＜0.05). Compared with the hypoxia group, the apoptosis rate of N9 cells and PC12 cells in the low, medium and high dose procaine groups decreased, the content of MDA and ROS decreased, the activity of SOD increased, the levels of TNF-α, IL-1β and IL-6 decreased, the expression of miR-369-3p decreased in a concentration dependent manner (P＜0.05). Compared with the anti-miR-con group, the apoptosis rate of N9 cells and PC12 cells in the anti-miR-369-3p group decreased, the content of ROS and MDA decreased, the activity of SOD increased, the levels of TNF-α, IL-1β and IL-6 decreased (P＜0.05). Compared with miR-con＋high dose procaine group, the apoptosis rate of N9 cells and PC12 cells in miR-369-3p＋high dose procaine group increased, the expression of cleaved Caspase-3 protein increased, the content of MDA and ROS increased, the activity of SOD decreased, the levels of TNF-α, IL-1β and IL-6 increased (P＜0.05). Conclusion Procaine can reduce hypoxia induced injury to N9 and PC12 cells, and its mechanism may be related to inhibiting the expression of miR-369-3p.