Abstract:Atherosclerotic diseases have become the leading cause of human death. Apelin/APJ receptors is widely found in the cardiovascular system, and is involved in the occurrence and development of a variety of cardiovascular diseases. Studies on the effects of Apelin/APJ system on atherosclerosis suggested that Apelin has dual effects on atherosclerosis. On the one hand, Apelin can promote the proliferation and migration of vascular smooth muscle cells and endothelial cells, and induce mononuclear cell adhesion to endothelial cells, which could promote angiogenesis, and affect the stability of As plaques. On the other hand, Apelin can antagoninize AngⅡ to regulate intracellular lipid metabolism, and reduce the generation of endothelial reactive oxygen species and cellular aging, prevent macrophages from turning into foam cells, and have a certain stabilizing effect on the As plaque that has been formed. In addition, it can also inhibit platelet activation, ultimately reducing the occurrence of atherosclerosis complications. Meanwhile, as a double-edged sword with protection or damage, autophagy may be one of the important targets of Apelin in atherosclerosis. This paper summarizes the research on Apelin/APJ system and atherosclerosis in the above aspects, and explores the possibility of Apelin/APJ receptor as a target for preventing or treating atherosclerosis.

Abstract:Aim To study the role and mechanism of dehydroepiandrosterone (DHEA) in the proliferation of vascular smooth muscle cells (VSMCs) induced by angiotensin Ⅱ (AngⅡ). Methods VSMCs were cultured with AngⅡ in vitro, then treated with DHEA. The effect of DHEA on the proliferation of VSMCs induced by AngⅡ was detected by MTS and cell counting. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effects of DHEA on the expressions of proliferating cell nuclear antigen (PCNA), Krüppel-like factor 5 (KLF5) and inducible nitric oxide synthase (iNOS) in AngⅡ-induced VSMCs. The effect of DHEA on the concentration of peroxynitrite anion (ONOO－) in the medium of AngⅡ-induced VSMCs was examined by enzyme-linked immunosorbent assay (ELISA). Endogenous iNOS was knocked down by transfecting VSMCs with iNOS-specific siRNA (si-iNOS) or nonspecific siRNA (si-Ctrl), and then treated the cells with or without DHEA; Western blot was performed to examine the expression of PCNA. Results The results of MTS and cell counting showed that DHEA could significantly inhibit the proliferation of VSMCs induced by AngⅡ (P＜0.05). The results of qRT-PCR and Western blot showed that DHEA significantly inhibited the expressions of PCNA, KLF5 and iNOS in VSMCs induced by AngⅡ at the level of protein and mRNA (P＜0.05). ELISA results showed that DHEA could reduce the concentration of ONOO－ in culture medium of VSMCs treated with AngⅡ (P＜0.05). Western blot results suggested that DHEA had no effect on AngⅡ-induced PCNA protein expression after knocked down endogenous iNOS (P＞0.05). Conclusion DHEA may inhibit the proliferation of VSMCs induced by AngⅡ probably through down-regulation of KLF5 expression by inhibiting ONOO－ produced by iNOS.

Abstract:Aim To investigate the effect of over-expression of Atg5 protein on the degree of macrophage foam.Methods Raw264.7 macrophages were infected with Atg5 lentivirus and control virus. The control cell line (control group) and the Atg5 over-expression cell line (observation group) were established. Two groups of cells were added 50 mL/L ox-LDL (oxidized low-density lipoprotein) respectively to induce the formation of frothy cells. The levels of protein p62, LC3, CD36 and SR-A were analyzed by western blot. The changes of intracellular cholesterol metabolism (cholesterol CE, free cholesterol FC and total cholesterol TC) were detected by HPLC (high performance liquid chromatography).The contents of lipid droplets in the two groups were analyzed by immunofluorescence and electron microscopy. The levels of inflammatory factors including TNF-α, IL-6 and IL-1 beta were detected by ELISA in cell culture supernatants of two groups. Results Compared with the control group, the level of the autophagic substrate p62 was significantly down-regulated and the level of LC3-II was significantly up-regulated in the observation group (P<0.05). Compared with the control group, the contents of CE, FC and TC of macrophages in the observation group significantly decreased (P<0.05).The level of cell lipid and the number of lipid droplets in the observation group were significantly lower than those in the control group (P<0.05). Compared with the control group, the levels of inflammatory cytokines TNF-α, IL-6 and IL-1 beta in the observation group were significantly down-regulated (P<0.05).Conclusions The over-expression of Atg5, autophagy core protein, can significantly enhance the autophagy level of macrophages. The Atg5 may degrade intracellular cholesterol and other lipids to prevent macrophage froth, thus reducing the occurrence of atherosclerosis.

Abstract:Aim To investigate the effect of Xuezhikang (XZK) on apoptosis induced by oxidized low density lipoprotein (ox-LDL) and its possible mechanism. Methods Human umbilical vein endothelial cells (HUVEC) were cultured and divided into three groups, namely control group, ox-LDL group and ox-LDL+XZK(different dosages)groups.Cell counting kit-8 was used to test cell survival, Annexin V-FITC/PI apoptosis detection kit was used to count apoptotic rate of HUVEC among different groups, reactive oxygen species (ROS) were detected by ROS assay kit, expression of cytochrome C (CytC), caspase-3 and PARP-1 were analyzed by Western blot. Results XZK (25 mg/L, 50 mg/L and 100 mg/L) showed an antagonistic effect on apoptosis and ROS production of HUVEC induced by ox-LDL, and 100 mg/L XZK downregulated the protein expression of CytC, caspase-3 and PARP-1. Conclusion XZK reduces ROS production, leading to less expression of CytC, caspase-3 and PARP-1, thus prevents mitochondrial apoptotic signaling from activating, and eventually protects HUVEC from apoptosis.

Abstract:Aim To investigate the effect of carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) on the expression of coxsackie and adenovirus receptor (CAR) and secondary myocardial injury after coxsackievirus B3 (CVB3) infection. Methods The overexpressed mouse CC1 recombinant virus was constructed, and the recombinant lentivirus pLVX-CEACAM 1-ZsGreen-Puro (rLV-CEACAM 1) was packaged and the biological titer of lentivirus was determined. It was divided into CC1 normal cell group, CC1 overexpression group, CC1 normal +CVB3 group and CC1 overexpression+CVB3 group. The apoptosis rate of cardiomyocytes was detected by AnnxinV-PE/ 7-AAD double staining in each group, and cell activity was detected by CCK8. The expression of CAR gene was detected by qPCR. The expression of CAR protein was detected by Western blot, tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) were measured by ELISA. Results (1)Recombinant vector sequencing CEACAM1 showed a gene sequence connection, which proved mice CEACAM1 recombinant virus vector was built, determination of recombinant lentivirus was 1.5×10¹¹ TU/L. (2)Apoptosis rate of cardiac myocytes in CC1 overexpression+CVB3 group was significantly higher than that in other groups, and the proliferation rate of cardiac myocytes was the lowest (P<0.05). (3)Relative expression of CAR gene was the highest in CC1 overexpression+CVB3 group, and the lowest in CC1 normal group. Relative expression of CVB3 was significantly higher in CC1 overexpression group than in CC1 normal group (P<0.05). (4)Level of TNF-α, IL-1β were higher in CC1 overexpression group, which increased significantly after CVB3 infection. Conclusion CC1 may promote the expression of CAR in cardiac tissue or cell after CVB3 infected cardiac myocytes. CAR might be a potential target for CC1 to regulate the process of cardiac injury caused by CVB3 infection.

Abstract:Aim To investigate the effects of ginsenoside Rg1 on arrhythmia after myocardial ischemia reperfusion (I/R) in rats based on peroxisome proliferator-activated receptor-γ(PPAR-γ). Methods 72 SD rats were randomly divided into sham-operated group (SO group), ischemia-reperfusion group (I/R group), ginsenoside Rg1 group (Rg1 group), ginsenoside Rg1 + rosiglitazone group (Rg1 + ROS group). The left anterior descending coronary artery was ligated in the last three groups to establish I/R model. The SO group and I/R group were given saline intervention, the Rg1 group was given 40 mg/kg ginsenoside Rg1 intervention, and the Rg1 + ROS group was given 40 mg/kg ginsenoside Rg1 + 6 mg/kg ROS intervention. ECG was monitored during 6 hours of reperfusion. Myocardial I/R area, myocardial enzymes, inflammatory cytokines and expressions of nuclear factor-κB (NF-κB), inhibitor of NF-κBand PPAR-γ were detected after 6 hours of reperfusion. Results Compared with SO group, arrhythmia in I/R group significantly aggravated, myocardial I/R area, the contents of creatine phosphate kinase (CK), creatine phosphate kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), P-selectin, E-selectin and the expression of NF-κB, PPAR-γ significantly increased, while the expression of I-κB expression significantly decreased. Compared with I/R group, arrhythmia in Rg1 group significantly improved, the contents of myocardial I/R area, CK, CK-MB, LDH, TNF-α, IL-1β, P-selectin, E-selectin and the expression of NF-κB, PPAR-γ significantly decreased, while the expression of I-κB expression significantly increased; Compared with Rg1 group, the arrhythmia of Rg1+ROS group significantly aggravated, the contents of myocardial I/R area, CK, CK-MB, LDH, TNF-α, IL-1β, P-selectin, E-selectin and the expression of NF-κB, PPAR-γ significantly increased, while the expression of I-κB expression significantly decreased. Conclusion Ginsenoside Rg1 can improve myocardial arrhythmia after I/R by inhibiting PPAR-γ-mediated inflammation.

Abstract:Aim To assess the degree of improvement in the quality of life of coronary heart disease patients with chronic total occlusion(CTO) and decreased left ventricular ejection fraction(LVEF) one month after percutaneous coronary intervention(PCI) therapy. Methods 111 CTO coronary heart disease patients who received PCI successfully were included prospectively and continuously in this study. All these patients were divided into two groups, according to their results of preoperative LVEF. In one group(n=67) the LVEF of patients was normal(≥50%) while patients in another group(n=44) had a decreased LVEF(<50%). Questionnaires were conducted in these patients with SF-12 Health Survey and Seattle Angina Questionnaire(SAQ)48 hours before PCI, and it recorded the clinical data(age, gender, BMI, blood pressure, heart rate, LVEF, education, hospitalization days, medical history, PCI status and medicine, etc.). One month after PCI, SF-12 Health Survey and SAQ were conducted in these patients and the degree of improvement in quality of life was evaluated. Results All 111 CTO patients received successful PCI. Patients in group B were older and had a faster heart rate, longer hospital stays and a higher percentage of diabetes history(P<0.05).The occurrence of major adverse cardiac events one month after PCI in two groups are similar(P>0.05). NYHA cardiac functional class was significantly improved in both groups(P<0.01). The SF-12 Health Survey and SAQ scores of patients in group B were significantly higher one month later than those before the PCI(P<0.05), and the SF-12 Health Survey and SAQ scores of patients in group A also increased significantly in all aspects except the dimension of treatment satisfaction of SAQ(P<0.05). In addition, the SF-12 health survey and SAQ scores in group B were close to those in group A(P>0.05). Conclusion Successful PCI can significantly improve the short-term quality of life of CTO coronary heart disease patients with decreased LVEF, and the degree of improvement is close to that of patients with normal LVEF.

Abstract:Aim To observe whether a combined thrombus burden reduction therapy during primary percutaneous coronary intervention (PCI), could improve microcirculation and enhance cardiac function in the long-term.Methods Anterior wall ST-elevation myocardial infarction(STEMI) patients with high thrombus burden were randomly assigned to receive a combined thrombus burden reduction therapy or thrombus aspiration alone. The combination of thrombus aspiration, intracoronary injection with 100 thousand units of urokinase, 5 mL tirofiban, and 200 μg nitroglycerin was performed in the experimental group, the control group was treated with thrombus aspiration. The primary end points included the percentage of patients with TIMI myocardial perfusion grade(TMPG) 3, ST segment resolution(STR) above 70%, the index of microcirculatory resistance (IMR) and left ventricular ejection fraction (LVEF) difference. The compound end points were heart failure, recurrent angina, recurrent myocardial infarction and sudden cardiac death as secondary end points. And it used bleeding academic research consortium(BARC) to define bleeding as the security point. Results 22 patients in the combined interventional group and 24 in the control group completed 1-year follow-up. The percentages of patients with TMPG 3 (68.2% vs 33.3%, P=0.006) and STR above 70% (63.6% vs 25.0%, P=0.016) were significantly higher in the combined group. IMR was significantly lower in the combined interventional group ((31.50±13.39) U vs (62.72±22.80) U, P=0.002). At 3 months and 1 year, the overall LVEF value was better in the combined interventional group (42.1% vs 40.0%, P=0.049; 41.9 % vs 39.8 %, P=0.042), respectively. At secondary end points, there were no significant difference in heart failure, recurrent angina, recurrent myocardial infarction and sudden cardiac death. There was no significant difference in bleeding between the two groups defined by BARC. Conclusion A combined thrombus burden reduction therapy during primary PCI can safely reduce thrombus burden, improve myocardial tissue perfusion, and improve cardiac function among STEMI patients with high thrombus burden.

Abstract:Aim To investigate the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and perioperative myocardial injury (PMI) in elderly patients with coronary heart disease and its predictive value. Methods From January 2016 to June 8,0 elderly patients with coronary heart disease who underwent PCI in our hospital were included in the study. Baseline data of patients were collected, and cardiac troponin T (cTnT), high-sensitivity C-reactive protein (hs-CRP), Lp-PLA2 and other biochemical parameters were measured before and after PCI operation. According to whether cTnT was elevated or not after PCI operation, the patients were divided into control group (55 cases without elevation of cTnT) and observation group (45 cases with elevation of cTnT). Clinical data and intraoperative status of PCI were compared between the two groups. Logistic regression was used to analyze the risk factors of PMI.Results There were no significant differences in hypertension, diabetes, smoking, PCI, statins use, high density lipoprotein cholesterol, low density lipoprotein cholesterol, creatinine and N-terminal pro-B-type natriuretic peptide between the two groups (P＞0.05). The level of apolipoprotein B in observation group was higher than that in control group (P＜0.05). The levels of Lp-PLA2 and hs-CRP in the observation group were significantly higher than those in the control group (P＜0.05). Gensini integral, stent number, stent release pressure and operation time in observation group were significantly higher than those in control group (P＜0.05). Logistic regression analysis showed that Lp-PLA2 (OR 4.5,5%CI 1.43-14.47), Gensini score (OR 1.8,5%CI 1.01-1.14), stent number (OR 5.5,5%CI 2.04-14.01) and operation time (OR 1.6,5%CI 1.00-1.12) were risk factors for PMI. Conclusion Preoperative elevation of Lp-PLA2 is a risk factor for PCI-related myocardial injury in elderly patients with coronary heart disease and has predictive value for PMI.

Abstract:Aim To explore the relationship between atherogenic index (AI) and serum anti-cardiolipin antibody (ACA) and anti-β2 glycoprotein 1 antibody (aβ2GP1), and to provide reference for the prevention and control of atherosclerosis (As). Methods 34 598 hospital patients were selected from the First Affiliated Hospital of Wenzhou Medical University from March 2017 to June 2018. Serum ACA, ACA-IgA, ACA-IgG, ACA-IgM, aβ2GP1, aβ2GP1-IgA, aβ2GP1-IgG, aβ2GP1-IgM, total cholesterol, high density lipoprotein cholesterol, homocysteine (Hcy) and apolipoprotein A1 (ApoA1) were detected. AI was calculated and the patients were divided into high-risk group (AI≥4) and low-risk group (AI＜4) according to AI. Correlation analysis was performed by statistical software. Results The positive rates of ACA and aβ2GP1 in high-risk group were higher than those in low-risk group (χ²＝23.276 and 17.603, all P＝0.000), and the levels of age, ACA-IgA, ACA-IgG, aβ2GP1-IgA, aβ2GP1-IgG and Hcy in high-risk group were also higher than those in low-risk group (all P＜0.05), while the level of ApoA1 was lower than that in low-risk group (P＝0.000). The correlation analysis showed that AI was positively correlated with ACA-IgA, ACA-IgG, aβ2GP1-IgA, aβ2GP1-IgG and Hcy (r＝0.8,0.2,0.4,0.4,0.142, all P＜0.01), and negatively correlated with ApoA1 (r＝－0.447, P＝0.000). Multivariate Logistic regression analysis showed that age, ACA-IgA, Hcy and aβ2GP1 were risk factors for As, and ApoA1 was protective factor for As. Conclusion With the increase of ACA-IgA, aβ2GP1, Hcy and age, the decrease of ApoA1, AI gradually increases, and As risk increases accordingly. Clinically, we should pay close attention to the elderly patients with abnormal ACA, aβ2GP1, Hcy and ApoA1 in order to prevent the occurrence of As.

Abstract:Aim To investigate the effect of improved door-to-balloon (D2B) time on outcomes in patients diagnosed with ST-segment elevation myocardial infarction (STEMI) in non percutaneous coronary intervention (PCI) centers. Methods A total of 200 STEMI patients within 12 h presenting were enrolled. D2B time, first medical contact-to-balloon (FMC2B) time and symptom-to-balloon (S2B) time were recorded. According to D2B time, all patients were divided into D2B<60 group (n=148) and D2B≥60 group (n=52). FMC2B time and S2B time were compared between the two groups. Major adverse cardiac and cerebral events (MACCE, including cardiogenic death, non-fatal myocardial infarction, non-fatal stroke, re-admission of unstable angina or heart failure) and all-cause mortality during follow-up of two groups were observed. Cox regression analysis was used to explore the association of D2B time and MACCE. Results D2B<60 group had shorter FMC2B time and S2B time than D2B≥60 group (P=0.013; P=0.027). Compared to D2B≥60 group, D2B<60 group had lower MACCE and all-cause mortality (P=0.008; P=0.047). Cox regression analysis showed that a D2B time less than 60min was an independent factor associated of MACCE (HR 0.0,5%CI 0.224~0.862, P=0.017). Conclusion A D2B time less than 60min can shorten symptom-to-balloon time and improve MACCE and all-cause mortality in STEMI patients not presenting in PCI center.

Abstract:Aim To explore the feasibility, effectiveness and safety of double-stent thrombectomy in the treatment of acute basilar artery occlusion. Methods Five patients with cerebral infarction caused by acute basilar artery occlusion with heavy thrombus load were retrospectively analyzed. The patients were treated with Solitaire FR double-stent arallel thrombectomy. The operation time, blood flow reperfusion immediately after thrombectomy, 24-hour improvement of nerve function and mRS score of 90-day follow-up after thrombectomy were evaluated. Results Good recanalization of occluded vessels was achieved in five patients by double-stent arallel thrombectomy. The modified thrombolysis in cerebral infarction (mTICI) grading of the patients was 2b-3 grade, of which 4 cases were completely recanalized (mTICI 3 grade). No obvious complication related to operation was found. NIHSS score decreased by 10 points 24 hours after operation compared with that before operation. With follow-up of 90 days after operation, two patients had good prognosis, two were disabled and one died. Conclusion Solitaire FR double-stent arallel thrombectomy is safe and effective in the treatment of acute cerebral infarction patients with partial posterior circulation and heavy thrombosis load.

Abstract:MicroRNA(miR)have been considered as the important regulators in both physiological and disease contexts, among which miR-34a has drawn great attention as its multiple functions in cardiovascular disease. It is reported that miR-34a is either upregulated or downregulated in atherosclerotic cardiovascular diseases, etc. This article reviews both the roles and mechanisms of miR-34a in cardiovascular diseases, aiming to provide new ideas for further researches on biomarkers and treatment target of cardiovascular disease.

Abstract:There are overwhelming epidemic evidences that both an elevated concentration of low-density lipoprotein cholesterol (LDLC) and a low concentration of high-density lipoprotein cholesterol (HDLC) are independent risk factors of atherosclerotic cardiovascular disease (CVD). Theoretically, the level of HDLC will rise when cholesteryl ester transfer protein (CETP) is inhibited, leading to treatment of CVD. To date, the results of basic and clinical studies on CETP are not consistent. Perhaps it is not an easy choice for drugs based on inhibition of CETP. The paper illustrates the physiological role of CETP in lipid metabolism, the relationship between CETP and atherosclerosis in some animal studies, and the phase Ⅲ clinical trial of the effects of CETP inhibitors on cardiovascular disease. It will review current status of CETP inhibitors in details.

Abstract:Obstructive sleep apnea hypopnea syndrome(OSAHS) is characterized by recurrent hypoxemia and hypercapnia at night. Recent fingdings show that OSAHS is closely associated with atherosclerosis cardiovascular disease(ASCVD)such as stroke,heart failure. And carotid intima-media thickness(CIMT)can predict ASCVD. So it is significant for preventing atherosclerosis(As) in OSAHS patients to study the relationship between IMT and OSAHS. This review summarized the recent research progress on the relationship between obstructive sleep apnea hypopnea syndrome and carotid intima-media thickness, including human epidemiological and related mechanism studies and related treatments. It can provide a background reference for interrupting the progress of As in OSAHS patients.

Abstract:Currently, low density lipoprotein(LDL) is the main intervention target for coronary heart disease(CHD) prevention and treatment. However, many patients with LDL in the normal range will still develop coronary atherosclerosis. Therefore, domestic and foreign researchers further studied the LDL subgroup and found that small dense low density lipoprotein(sd-LDL) has a stronger atherogenic effect than LDL. sd-LDL, as an independent risk factor of CHD, is more sensitive than LDL. In the past, due to the limitations of detection methods, the detection of sd-LDL has not been widely applied to clinical practice. In recent years, the presence of homogeneous enzyme makes it possible to be used as a clinical routine test. sd-LDL, as a risk factor of CHD, is closely related to its occurrence and development. In the future, more large intervention studies will be conducted to determine the appropriate target level of sd-LDL, and more accurate and effective cardiovascular risk assessment and management treatment will be conducted. This paper reviews the advances in sd-LDL and its relationship with CHD.