Abstract:Atherosclerosis is a chronic inflammatory vascular disease with complicated pathogenesis involving multiple cells and molecules. Semaphorin is a family of secreted, transmembrane, and GPI-anchored axon signaling proteins that play an important role in many pathophysiological processes by binding to their receptors neuropilin and plexin, such as nerve growth, immune response, tumor metastasis, angiogenesis, and metabolic disease. Studies on the cellular and molecular mechanisms of semaphorin in atherosclerosis have been progressed in the past decade. This article summarizes the research progress on the role of semaphorin in the development of atherosclerosis, focusing on how semaphorin affect vascular cells and blood cells, and regulate angiogenesis.

Abstract:Myocardial fibrosis is the excessive deposition of extracellular matrix(ECM) in the cardiac interstitium caused by a variety of injury factors, which can lead to the decline of ventricular compliance, myocardial diastolic and systolic dysfunction and arrhythmia. It is closely related to the severity of cardiac insufficiency and poor prognosis. Fibroblasts, endothelial cells, pericytes and immune cells in cardiac interstitium can be divided into a variety of subgroups due to different genomic expression, and regulate myocardial fibrosis through phenotypic transformation, fine regulation of ECM components and secretion of pro-fibrosis or anti-fibrosis factors. This article reviews the role of cardiac interstitial cells in cardiac fibrosis and reveals the molecular mechanisms including signal transduction networks and epigenetic modifications, which will provide new therapeutic strategies and targets for preventing and alleviating cardiac fibrosis.

Abstract:Aim To study the protective effect of growth hormone releasing hormone receptor agonist MR409 on vascular calcification (VC) in gene deficient mice Db/Db diabetic mice (Db/Db mice). Methods With 12-week-old male wild-type (WT) C57BL/6 mice as the WT group (control group), 12-week-old male Db/Db mice were randomly divided into Db/Db group (diabetes group) and MR409 group (MR409 treatment group). MR409 group was given MR409 (15 μg/time) every other day for 8 weeks. At the end of the 8th week, the mouse serum alkaline phosphatase (ALP) and blood glucose levels were tested. HE staining was used to observe the morphological changes of aorta in mice. Calcium salt deposition in aorta was detected by von Kossa staining and alizarin red staining. Endothelium-dependent vasodilation function was measured by in vitro vascular perfusion system. Aortic calcification-related protein Runt-related transcription factor 2 (Runx2) protein expression was detected by immunohistochemical staining. Aortic reactive oxygen species (ROS) level was detected by dihydroethidium fluorescent staining. Results Compared with WT group, serum ALP activity increased, blood vessel wall thickness increased, vasodilation function decreased, and aortic ROS level increased in Db/Db group (P＜0.05). Compared with Db/Db group, ALP activity decreased, aortic hypertrophy decreased, vasodilation function improved, and ROS level of aorta decreased in MR409 group (P＜0.05). Compared with WT group, there was significant VC in Db/Db group, which showed increased calcium salt deposition and increased Runx2 protein expression in aorta (P＜0.05). Compared with Db/Db group, calcium salt deposition and Runx2 protein expression in aorta were decreased in MR409 group (P＜0.05). Conclusion MR409 can significantly inhibit VC, reduce aortic hypertrophy and improve vascular endothelial function in diabetic mice, and its mechanism may be related to the inhibition of the increase of Runx2 expression induced by oxidative stress.

Abstract:Aim To explore the regulatory effect of nicotinamide mononucleotide (NMN) on cholesterol in Huh7 cells and its molecular mechanism. Methods Huh7 cells were treated with different concentrations of NMN (0,2.5,5, 0,0, 200 μmol/L) for 24 hours, and the cell viability was detected by cell counting kit-8 (CCK-8). The lipid accumulation in cells was observed by oil red O staining. The uptake ability of cells to DiI-LDL was observed by immunofluorescence microscope. Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expressions of mRNA and protein of intracellular hepatocyte nuclear factor 1α (HNF1α), proprotein convertase subtilisin kexin 9 (PCSK9), and low density lipoprotein receptor (LDLR). Results CCK-8 experiment showed that different concentrations of NMN had no significant effect on cell viability. Oil red O staining showed that the number of orange-red lipid droplets in the cells increased with the increase of NMN concentration after the addition of LDL. Immunofluorescence microscope observation results showed that the red fluorescence around the nucleus increased with the increase of NMN concentration. Western blot and qRT-PCR results showed that 100 and 200 μmol/L NMN significantly reduced the expressions of PCSK9 and HNF1α mRNA and protein, and significantly increased the expressions of LDLR mRNA and protein in Huh7 cells (P＜0.01). Conclusion NMN may be involved in regulating the cholesterol metabolism of Huh7 cells by mediating the HNF1α/PCSK9/LDLR signaling pathway, and enhance the uptake capacity of LDL by liver cells.

Abstract:Aim To investigate the effects of atorvastatin (Ato) on homocysteine (Hcy)-induced mitogen extracellular signal-regulated kinase (MEK)/extracellular regulatory protein kinase (ERK) pathway and myocardial mitochondrial damage in H9c2 cardiomyocytes. Methods Cell counting kit-8 (CCK-8) was used to detect the effect of different concentrations of Hcy on the survival rate of H9c2 cells to screen the induction concentration and time of Hcy. H9c2 cells were divided into model group, 5 μmol/L Ato group, 10 μmol/L Ato group and 15 μmol/L Ato group, and another normal H9c2 cells were taken as control group. The apoptosis rate was detected by flow cytometry; the change of mitochondrial membrane potential was detected by JC-1 method; the level of intracellular reactive oxygen species (ROS) was measured by DCFH-DA method; enzyme linked immunosorbent assay (ELISA) was used to detect the contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT); and the phosphorylation levels of MEK1/2 and ERK1/2 were detected by Western blot. Results Compared with control group, 2 μmol/L Hcy significantly reduced the survival rate of H9c2 cells (P＜0.05), so that, in this study, H9c2 cells were treated with 2 μmol/L Hcy for 24 h. Compared with control group, the apoptosis rate, ROS level and MDA content of H9c2 cells were significantly increased in the model group (P＜0.05), and the mitochondrial membrane potential, SOD, CAT contents and phosphorylation levels of MEK1/2 and ERK1/2 were significantly decreased (P＜0.05). Compared with model group, the apoptosis rate, ROS level and MDA content of H9c2 cells in 5 μmol/L Ato group, 10 μmol/L Ato group and 15 μmol/L Ato group decreased in turn (P＜0.05), and the mitochondrial membrane potential, SOD, CAT contents and phosphorylation levels of MEK1/2 and ERK1/2 increased in turn (P＜0.05). Conclusion Ato may reduce the oxidative stress induced by Hcy in H9c2 cells by activating MEK/ERK pathway and alleviate myocardial mitochondrial damage.

Abstract:Aim To explore the differential risk assessment of acute aortic syndrome (AAS) and non-ST-segment elevation myocardial infarction (NSTEMI) in patients with chest pain less than 3 hours. Methods 69 patients with AAS and 136 patients with NSTEMI were retrospectively analyzed. The data of the two groups were statistically analyzed and the differences between the two groups were compared. Univariate and multivariate Logistic regression analysis were used to evaluate the differential risk factors of AAS and NSTEMI. The area under curve (AUC) of receiver operating characteristic (ROC) of differential risk factors was compared. The value of each factor in distinguishing AAS and NSTEMI was analyzed, and the best cut-off value of partial difference risk factors was determined. Results Multivariate Logistic regression analysis showed that D-dimer (OR 8.2,5% CI 4.064～19.366), platelet distribution width (PDW) (OR 1.5,5% CI 1.253～2.133), unconjugated bilirubin (UCB) (OR 1.9,5% CI 1.003～1.317), systolic blood pressure (SBP) (OR 1.5,5% CI 1.006～1.045) were higher risk factors of AAS compared with NSTEMI. ROC curve analysis showed that AUCD-dimer＝0.944 (95%CI 0.897～0.973) and AUCPDW＝0.794 (95%CI 0.724～0.853). The optimal cut-off value of D-dimer and PDW in identifying AAS from NSTEMI was determined by using the Youden index of ROC curve. The cut-off point of ROC curve of D-dimer was 247.5 μg/L, the sensitivity was 95.7%, and the specificity was 83.8%; The cut-off point of ROC curve of PDW was 16.05%, the sensitivity was 58.8%, and the specificity was 95.6%. Conclusions D-dimer, PDW, UCB and SBP are the differential risk factors of AAS and NSTEMI. When D-dimer is lower than 247.5 μg/L, AAS can be effectively excluded, and when PDW is higher than 16.05%, AAS will probably occur.

Abstract:Aim Patients with ST-elevation myocardial infarction (STEMI) were subjected to administer ischemic post-conditioning (IPOC) before conducting emergency treatment with percutaneous intervention (PCI). Changes in serum soluble apoptosis factor (sFas) and soluble apoptosis factor ligand (sFasL) and the left ventricular ejection fraction (LVEF) under echocardiography during the 1 postoperative year were investigated in patients, and changes in cardiac function in patients and the possible mechanisms were explored. Methods 90 patients with acute STEMI who underwent emergency PCI were randomly divided into three groups before treatment:routine PCI group, IPOC 45 s group and IPOC 60 s group. No intervention was given within 3 minutes after reperfusion of infarct-related artery (IRA) in routine PCI group. Within 1 minute after the opening of IRA, repeated low pressure (4～6 standard atmospheric pressure) filling and retraction of the balloon were performed at the upstream of the patient's blood vessels for 3 times, each time lasting 45 s. The operation method of the IPOC 60 s group was the same as that of the IPOC45 s group, lasting 60 s each time. The levels of serum sFas and sFasL were measured before operation and 0 h, 24 h and 48 h after operation, and the changes of LVEF in the three groups were followed up for 1 month, 3 months, 6 months and 1 year. Results There was no significant difference in serum sFas, sFasL level among the three groups before operation and 0 h, 24 h after operation (all P＞0.05). 48 hours after operation, the serum sFas, sFasL level decreased significantly in the IPOC 60 s group and the IPOC 45 s group compared with the routine group (all P＜0.05). There was no significant difference in LVEF values among the three groups at 1 week, 1 month and 3 months after operation(all P＞0.05), but at 6 months after operation, the values of LVEF in IPOC 60 s group and IPOC 45 s group were higher than those in routine group. One year after operation, the value of LVEF in IPOC 60 s group was higher than that in routine group(P＜0.05). Conclusion Ischemic postconditioning 60 s reperfusion therapy after ischemia can significantly improve cardiac function in STEMI patients, and the mechanism may be related to the inhibitory effect of IPOC on apoptosis induced by myocardial reperfusion.

Abstract:Aim To investigate the effects of argatroban combined with edaravone on the recovery of neurological function and serum homocysteine (Hcy), CXC chemokine ligand 16 (CXCL16), and transforming growth factor-β1 (TGF-β1) in patients with posterior circulation acute cerebral infarction. Methods A total of 123 patients with acute cerebral infarction of the posterior circulation who were admitted to our hospital from January 2017 to March 2019 were selected as the research objects. According to the random number table, they were divided into combined treatment group, argatroban group, and edaravone group, with 41 cases in each group. On the basis of routine symptomatic treatment such as oxygen inhalation, infection prevention, anticoagulation, and plaque stabilization, the argatroban group was given argatroban, the edaravone group was given edaravone, and the combined treatment group was given argatroban and edaravone. After 14 days of treatment, comparing the therapeutic effect, hemodynamic index of the posterior circulation (post-cerebral artery, vertebral artery, basilar artery systolic peak blood flow velocity (Vs), resistance index (RI)), serum brain injury markers (neuron-specific enolase (NSE), polyamine oxidase (PAO), S-100β protein), serum inflammatory factors (Hcy, CXCL16, TGF-β1) levels, nerve function (NIHSS scores), daily living ability (ADL scores) before and after 14 days of treatment and adverse reactions of the three groups. Results The total effective rate of the combined treatment group was higher than that of argatroban group and the edaravone group. After 14 days of treatment, the NIHSS scores and ADL scores were better in combined treatment group than those of the argatroban group and edaravone group (P＜0.05). There was no significant difference in the incidence of adverse reactions among the three groups (P＞0.05). After 14 days of treatment, the Vs of the posterior cerebral artery, vertebral artery, and basilar artery of the three groups increased, and it was higher in combined treatment group than that in argatroban group and edaravone group, and the RI decreased, and it was lower in combined treatment group than that in argatroban group and edaravone group. After 14 days of treatment, serum NSE, PAO, and S-100β levels in the three groups decreased, and the combined treatment group decreased the most (P＜0.05). After 14 days of treatment, the levels of serum Hcy, CXCL16 and TGF-β1 in three groups decreased, they were lower in combined treatment group than those in argatroban group and edaravone group (P＜0.05).Conclusion Agatroban combined with edaravone is effective in the treatment of posterior circulation acute cerebral infarction, which can effectively improve the state of cerebral blood flow, suppress nerve damage, at the same time ease the body's inflammation, improve the patient's nerve function and daily life ability, and ensure the safety of treatment.

Abstract:Aim To explore the predictive value of plasma microRNA-93 (miR-93) level for in-stent restenosis (ISR) after interventional therapy in patients with lower extremity arteriosclerosis obliterans (LASO). Methods 184 patients with LASO admitted to the Affiliated Hospital of North China University of Technology from February 2016 to May 2019 were selected as the research objects. According to whether the patients with LASO had ISR within one year after intervention, they were divided into two groups:ISR group (n＝71) and non-ISR group (n＝113). Real-time fluorescence quantitative PCR was used to detect the plasma miR-93 level of LASO patients, and to explore the relationship between miR-93 and ISR. Results Comparing the plasma miR-93 levels between the ISR group and the non-ISR group, the differences between the two groups including time effect, inter-group effect, and time-to-group interaction effect were statistically significant (P＜0.01). The area under the receiver operating characteristic curve, sensitivity, and specificity of postoperative 14 days miR-93 in diagnosing ISR were 0.9,1.55%, and 70.80%, respectively, and its diagnostic efficiency for ISR was higher than those of preoperative miR-93 and postoperative 7 days miR-93, the differences were statistically significant (P＜0.001). Multivariate Logistic regression analysis showed that the length of vascular occlusion, postoperative 14 days miR-93, low density lipoprotein cholesterol and C-reactive protein were independent risk factors affecting ISR in LASO patients (P＜0.01). Restricted cubic spline fitting Logistic regression analysis showed that miR-93 was related to ISR in LASO patients (P＜0.001), and there was a non-linear relationship (P＝0.009). Conclusion Plasma miR-93 level in LASO patients is related to ISR, and the high level of plasma miR-93 at 14 days after interventional surgery suggests that LASO patients have a high risk of ISR within one year after operation.

Abstract:Aim To compare the long-term effects of drug-coated balloon angioplasty and drug-eluting stent implantation for left main bifurcation(LMB)-in-stent restenosis(ISR). Methods 48 patients with LMB-ISR, who underwent percutaneous coronary intervention (PCI) between October 2014 and October 2018, were retrospectively reviewed for the present study (repeat drug eluting stent (DES) implantation (n＝24), DCB angioplasty (n＝24)). Qualitative comparative analysis (QCA) was performed before and after PCI. Thirty-nine patients (81.3%) were followed up for 18 months to perform coronary angiography(CAG) and QCA, and long-term follow-up was conducted for clinical endpoint events. Results Analysis of the baseline characteristics showed that the patients in the DCB group had a similar incidence of non-ST segment elevation myocardial infarction/ST segment elevation myocardial infarction at the index PCI (8.3% vs 25.0%, P＝0.25), higher low-density lipoprotein cholesterol level ((92.9±35.1) mg/dL vs (78.0±30.7) mg/dL, P＝0.07), and more “stent- in-stent” lesions (25.0% vs 4.2%, P＝0.05) than those in the DES group but not statistically significant. After 18 months follow up ,QCA showed there was no significant difference between the DCB group and the DES group in the late lumen loss ((1.06±1.10) mm vs (0.84±1.15) mm, P＝0.62), and no significant difference in the minimum lumen diameter of target lesions ((1.68±0.96) mm vs (2.06±1.21) mm, P＝0.37). The cumulative incidence rates of major adverse cardiovascular events (MACE) were similar between both groups (median follow-up duration was 868 days; MACE rate was 25.0% in the DCB group and 29.2% in the DES group, P＝0.75). Conclusion DES and DCB showed comparable long-term clinical results in patients with LMB-ISR lesions.

Abstract:Aim To investigate the clinical manifestations, pathological and imaging features of eosinophilic granulomatosis with polyangiitis (EGPA) in order to improve the level of clinical diagnosis and treatment. Methods The clinical data of 13 patients with EGPA diagnosed in General Hospital of Chinese People's Liberation Army from January 2006 to April 2021 were analyzed retrospectively, including basic information, clinical manifestations, conditions of involved organs, hematology and imaging examinations, pathological examinations and treatments, and follow-up happening.Results Among the 13 patients with EGPA, 7 were males and 6 were females; aged from 27 to 60 years old, with a median age of 37 years. The involved organs include respiratory system, nervous system, digestive system, cardiovascular system, urinary system, skin, ear, nose, throat, eyes, and etc. Leukocytosis was found in 10 patients, and eosinophils (Eos) increasing was found in 11 patients. Elevated IgE was found in 10 patients. 6 cases were positive for antineutrophil cytoplasmic autoantibody. 10 cases of pathological examination showed obvious Eos infiltration. All patients were treated with hormone and immunosuppressant. 13 cases were followed up, 4 cases recurred and 1 case died. Conclusions The main clinical features of EGPA are increased Eos in peripheral blood and Eos infiltration in pathological tissues, involving multiple systems, especially the respiratory system. Pathological biopsy is helpful for diagnosis. Hormone and immunosuppressant are effective in the treatment of EGPA.

Abstract:Hyperlipidemia is an important risk factor for chronic cardiovascular and cerebrovascular diseases such as coronary heart disease and cerebral infarction, and the prevention and treatment of dyslipidemia has become one of the important methods for the prevention of coronary heart disease. At present, most of the indicators used to evaluate the efficacy of hyperlipidemia are total cholesterol, triglycerides, low density lipoprotein, high density lipoprotein and body weight. Atherosclerosis index, leptin, adiponectin, and total fecal bile acid are four new indicators used to evaluate the efficacy of hyperlipidemia. This paper reviews the four indicators for the evaluation in the treatment of hyperlipidemia.

Abstract:Acute coronary syndrome is a kind of acute cardiac ischemic syndrome. At present, the traditional cardiac markers such as troponin are widely used in clinic, but have limitation of poor specificity, low sensitivity and signal timeliness. This leads to misdiagnosis, missed diagnosis or delayed treatment of patients with acute chest pain, and the best opportunity for rescue treatment is missed. To this end, researchers have found some novel biomarkers with early diagnostic and predictive value for myocardial injury in acute coronary syndrome in recent years. This review will summarize the research progress of these novel myocardial injury markers in the early diagnosis of acute coronary syndrome patients.

Abstract:Revascularization is currently the most effective method for the treatment of myocardial ischemia. However, in the process of treatment, reperfusion of ischemic area accelerates the apoptosis of damaged cardiomyocytes, aggravates myocardial ischemia and hypoxia, and leads to myocardial ischemia reperfusion injury (MIRI). NADPH oxidase-2 (Nox2) generates reactive oxygen species (ROS) to induce oxidative stress and cause myocardial oxidative damage. ATP-sensitive potassium channel (KATP) plays an important role in cardiac protection by regulating energy consumption during MIRI and reducing ROS production in myocardial cells after ischemia reperfusion. This article reviews the recent research progress of Nox2 and KATP mediated MIRI, and explores the regulatory role of KATP on Nox2 in ischemia reperfusion cardiomyocytes.

Abstract:Atherosclerosis is the main cause of cardio-cerebrovascular related diseases. Among the influencing factors of atherosclerosis, angiogenesis is one of the main causes of plaque rupture and various complications. Hypoxia, inflammation and growth factor-related factors can cause angiogenesis in plaques and lead to atherosclerosis. This article reviews the related factors affecting angiogenesis and their mechanism, in order to provide new ideas and intervention targets for the prevention and treatment of atherosclerosis.