Abstract:Aim To explore the possible molecular mechanism of low density lipoprotein (LDL) oxidation. Methods Human monocyte line THP-1 cells were induced by natural LDL (100 mg/L) for 0,1, 3 and 5 hours. Induction of monocytes at different time points was for expression profile microarray experiments, and genes related to LDL oxidation were screened. Real-time quantitative PCR and Western blot were used to further validate the results of some microarrays at the levels of mRNA and protein, respectively. Gene clustering, biological functions and signal transduction pathways related to lipid and oxidation were analyzed by using the DAVID database. Results After LDL induced THP-1, the expression of a large number of genes related to biofilm in cells was changed, suggesting that lipid oxidation was localized on biofilm. The expression of lipid oxidation-related genes changed after 3 hours of LDL induction, which imply that lipid oxidation had begun. Functional annotation analysis of differentially expressed genes revealed that Toll-like receptor (TLR) signaling pathway, apoptosis, endocytosis, cell cycle, lipid raft, lipid binding, localization, transport, cell adhesion, metal ion homeostasis, redox and other biological pathways were enriched to varying degrees. The mRNA and protein expressions of inflammatory factors induced by natural LDL were inhibited at different time points in THP-1. For example, the expressions of tumor necrosis factor α, interleukin-33, c-FOS and other genes decreased gradually with the prolongation of incubation time of LDL. Conclusion This study suggests that the oxidation of natural LDL may be related to the recognition and inflammation signal transduction of TLR4-TLR10-CD36.

Abstract:Aim To investigate the effect of miR-92a-3p_R +1 and miR-92a-1-5p on phenotypic transformation and proliferation of rat vascular smooth muscle cells (VSMC) induced by oxidized low-density lipoprotein (ox-LDL) in the ERK 1/2 signaling pathway. Methods VSMC isolated from rats, and ox-LDL (50 mg/L) was used to induce VSMC.ERK1/2 inhibitors U0126(10 μmol/L)was used for intervention. The miRNA microarray profiling was performed using small RNA sequencing analysis. CCK-8 method and Brdu flow cytometry were used to detect VSMC proliferation. Immunofluorescence assay was performed to detect the expression of SM22α protein in VSMC. Western blot was used to detect the expression changes of ERK1/2 pathway signal molecules (ERK, p-ERK), phenotype marker protein SM22α and proliferation associated proteins such as PCNA, cyclin D1, p21 and p27. Results Under ox-LDL induction, the expressions of miR-92a-3p_R +1 and miR-92a-1-5p in VSMC were significantly up-regulated. After the intervention of ERK1/2 inhibitors U0126, the phosphorylation level of ERK1/2 was inhibited, the corresponding VSMC miR-92a-3p_R +1 and miR-92a-1-5p expression significantly lowered (P<0.05). Therefore, the study speculated that ERK1/2 signaling pathway may affect the phenotypic transformation and proliferation of VSMC by regulating the expression of miR-92a. After inhibiting the ERK1/2 signaling pathway, the proliferation of VSMC was significantly reduced, and the expression of SM22α was up-regulated (P<0.05). The expression of PCNA and cyclin D1 was down-regulated and the expression of p21 and p27 proteins were up-regulated (P<0.05). This indicated that the phenotypic transformation and proliferation were significantly inhibited. Conclusion Mir-92a-3p_R +1 and miR-92a-1-5p play important roles in the ERK1/ 2 signaling pathway that ox-LDL induces phenotypic transformation and proliferation of VSMC.

Abstract:Aim To investigate the effects of saggliptin on vascular endothelial cell injury induced by ox-LDL and expression of miR-590/TLR4/NF-κ B. Methods Human umbilical vein endothelial cells (HUVEC) were cultured and divided into control group, ox-LDL group, sagliptin group, sagliptin+miR-590 inhibitor group, NC mimic group, miR-590 mimic group, NC inhibitor group and miR-590 inhibitor group. The proliferation activity, the expression of miR-590/TLR4/NF-κB and the contents of tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in culture medium were measured. Results The expression of TLR4, NF-κB p65 in cells and the contents of TNF-α, IL-1β, ICAM-1, VCAM-1 in culture media of ox-LDL group were significantly higher than those of control group, cell proliferation activity and the expression of miR-590 in cells was significantly lower than that of control group; the expression of TLR4, NF-κB p65 in cells and the contents of TNF-α, IL-1β, ICAM-1, VCAM-1 in culture media of sagliptin group were significantly lower than those of ox-LDL group, cell proliferation activity and the expression of miR-590 was significantly higher than that of ox-LDL group; the expression of TLR4, NF-κB p65 in cells and the contents of TNF-α, IL-1β, ICAM-1, VCAM-1 in culture media of saglitine+miR-590 inhibitor group were significantly higher than those in saglitine group, cell proliferation activity and the expression of miR-590 was significantly lower than that of saglitine group; the expression of TLR4, NF-κB p65 in cells and the contents of TNF-α, IL-1β, ICAM-1, VCAM-1 in culture media of miR-590 mimic group were significantly higher than those of NC mimic group, the expression of TLR4, NF-κB p65 in cells and the contents of TNF-α, IL-1β, ICAM-1, VCAM-1 in culture media of miR-590 inhibitor group were significantly lower than those of NC inhibitor group. Conclusion Sagliptin can alleviate ox-LDL-induced vascular endothelial cell injury by the miR-590/TLR4/NF-κB pathway.

Abstract:Aim To study the protective effect and oxiracetam on rats with cerebral infarction and the role of HIF-1α/AMPK/HSP70 signaling pathway. Methods Adult male SD rats were randomly divided into sham group, cerebral infarction group, oxiracetam group, oxiracetam+YC-1 group, oxiracetam+8-bAMP group and oxiracetam+Que group. The model of cerebral infarction was established by thread embolization. Oxiracetam group was given tail vein injection of 200 mg/kg oxiracetam, Oxiracetam+YC-1 group, Oxiracetam+8-bAMP group, Oxiracetam+Que group were given tail vein injection of HIF-1α inhibitor YC-1, AMPK inhibitor 8-bAMP, HSP70 inhibitor Quercetin separately on the basis of Oxiracetam tail vein injection. After 14 days of intervention, cerebral infarction volume, behavioral parameters, oxidative stress index and HIF-1α/AMPK/HSP70 pathway molecule in brain were measured. Results Compared with cerebral infarction group, the volume of cerebral infarction significantly reduced, the standing time of balance beam and walking time of balance beam significantly prolonged, the contents of ROS, MDA, 8-OHdG in brain tissue significantly decreased, the contents of SOD and GPx and the expressions of Nrf2, HO-1, AMPK and HSP70 in brain tissue significantly increased. Compared with the oxiracetam + YC-1 group, oxiracetam + 8-bAMP group and oxiracetam + Que group, the contents of ROS, MDA, 8-OHdG in brain tissue significantly increased, the contents of SOD, GPx and the expression of Nrf2, HO-1 significantly decreased(P＜0.05). Conclusion Oxiracetam can alleviate cerebral infarction injury in rats by activating HIF-1α/AMPK/HSP70 pathway.

Abstract:Aim To investigate the effect of neuregulin-1(NRG-1) on alleviating hypoxia/reoxygenation (H/R) injury of cardiomyocytes through extracellular regulated protein kinase 1/2 (ERK1/2) pathway. Methods Myocardial H9c2 cell lines were cultured and randomly divided into control group treated with DMEM without drugs under conventional conditions, H/R group treated with DMEM without drugs under H/R conditions, NRG-1 group treated with DMEM containing NRG-1 under H/R conditions, and NRG-1+PD group treated with PD98059 containing NRG-1 and ERK1/2 inhibitors under H/R conditions. Then cell proliferation, apoptosis, apoptosis gene, inflammatory index, ERK1/2 were determined.Results The OD₄₉₀ level of H/R group was significantly lower than that of control group, the apoptotic rate, the expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, nuclear factor kappa B (NF-κB), ERK1/2 in cells and the contents of tumor necrosis factor alpha (TNF-α), interleukin 1beta (IL-1β), interferon gamma (IFN-γ) in culture medium were significantly higher than those of control group. The OD₄₉₀ level and the expression level of ERK1/2 in cells of NRG-1 group were significantly higher than those of H/R group, and the apoptotic rate, the expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, NF-κB in cells and the contents of TNF-α, IL-1β, IFN-γ in culture medium were significantly lower than those of H/R group. The OD₄₉₀ level and the expression level of ERK1/2 in cells of NRG-1+PD group were significantly lower than those of NRG-1 group, and the apoptotic rate, the expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, NF-κB in cells and the contents of TNF-α, IL-1β, IFN-γ in culture medium were significantly higher than those of NRG-1 group. Conclusion NRG-1 can alleviate H/R injury of cardiomyocytes by activating ERK1/2 pathway.

Abstract:Aim To explore the relationship between the expression of serum aquaporin 1 (AQP1), aquaporin 4 (AQP4), vascular endothelial growth factor (VEGF) and the severity of cerebral edema in patients with acute cerebral infarction. Methods 78 patients with acute cerebral infarction were selected as the observation group and 80 healthy people were selected as the control group, enzyme-linked immunosorbent assay was used to detect the levels of serum AQP1, AQP4 and VEGF, the severity of brain edema was judged by measuring the electrical impedance disturbance coefficient with non-invasive dynamic monitor. According to the electrical impedance disturbance coefficient, the observation group was divided into severe group (>9.5) and mild group (7.5

Abstract:Aim To investigate the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) for patients with acute coronary syndrome and high bleeding risk. Methods 108 patients with acute coronary syndrome and high bleeding risk and receiving PCI treatment were randomly divided into test group (bivalirudin group) and control group (heparin group), 54 cases in each group. TIMI blood flow, activated coagulation time (ACT), platelet count, platelet aggregation rate, high-sensitivity C-reactive protein (hs-CRP) and interleukin-4 (IL-4), 30-days bleeding events and major adverse cardiovascular events (MACE) were compared between the test group and the control group before and after operation. Results There was no significant difference in TIMI blood flow between the test group and the control group. The ACT compliance rate, platelet count, platelet aggregation rate, hs-CRP, IL-4 and other indicators in the test group were significantly better than those in the control group, and the differences were statistically significant (P＜0.05). The incidences of hemorrhagic events and MACE in the test group were significantly lower than those in the control group, and the differences were statistically significant (P＜0.05). Conclusion The application of bivalirudin during PCI for patients with acute coronary syndrome and high bleeding risk can significantly reduce the incidences of bleeding events and MACE, and has good safety.

Abstract:Aim To investigate the effect of ticagrelor on platelet reactivity and short-term prognosis in patients with unstable angina pectoris during perioperative period of percutaneous coronary intervention (PCI). Methods 424 patients with unstable angina pectoris were enrolled. They were randomly divided into two groups:(1)ticagrelor group (n＝212):treated with ticagrelor (load dose 180 mg, maintenance dose 90 mg, twice a day, oral); (2)clopidogrel group (n＝212):treated with clopidogrel (load dose 300 mg, maintenance dose 75 mg, once a day, oral). PCI was successfully performed in both groups, and domestic Firebird rapamycin drug-eluting stents were selected as stents. The platelet reactivity, cardiac troponin I (cTnI), a marker of myocardial injury during perioperative period of PCI, and the occurrence of adverse events 90 days after PCI were observed in two groups. Results There was no significant difference in cTnI level between the two groups after PCI (P＞0.05). The platelet aggregation rate induced by arachidonic acid and adenosine diphosphate in ticagrelor group was lower than that in clopidogrel group (P＜0.05). The ratio of high platelet reactivity induced by adenosine diphosphate in ticagrelor group was lower than that in clopidogrel group (P＜0.05). The incidence of recurrent myocardial ischemia within 90 days after PCI in ticagrelor group was lower than that in clopidogrel group (5.19% vs 16.04%, P＜0.05). There was no significant difference in hemorrhagic events between the two groups (P＞0.05). Conclusion Ticagrelor does not reduce the incidence of myocardial injury after PCI, but it has a stronger antiplatelet effect than clopidogrel, and reduces the incidence of recurrent myocardial ischemia events after PCI without increasing the risk of bleeding.

Abstract:Aim To investigate the carotid atherosclerosis risk factors of H-type hypertension. Methods A total of 240 hospitalized patients with primary hypertension from january 2017 to january 2018 were selected. According to the plasma homocysteine(Hcy) level, participators were divided into H-type hypertenion group(H-group, plasma Hcy＞10 μmol/L)with 118 cases and simple group(plasma Hcy≤10 μmol/L) with 122 cases. Patients' general information, biochemical index, carotid intima-media thickness(IMT), carotid atherosclerotic plaques and the condition of carotid stenosis, were compared between the two groups. Multivariate Logistic regression was used to analyze the risk factors of carotid atherosclerosis in H-group patients. Results Male composition, coronary heart disease history, stroke history, mean systolic blood pressure , pulse pressure, plasma Hcy, low density liporotein cholesterol(LDLC), urea nitrogen(BUN), creatinine(Cr) and uric acid(UA) levels, the detection rate of the carotid IMT, plaque formation, IMT, the plaque number≥3, carotid stenosis >50% in H group were significantly different from simple group(P＜0.05). Multivariate Logistic regression analysis demonstrated that aged, smoking history, high LDL were significantly associated with carotid IMT in H-type hypertension patients, with OR values 1.282(95%CI 1.133~1.451), 663(95%CI 1.200~ 20.669), 4.301(95%CI 1.199~15.434) respectively. Moreover, aged, overweight, high LDL with OR values 1.150(95% CI 1.069~1.238), 3.496(95%CI 1.353~9.033), 1.244(95%CI 1.014~1.526)were significantly associated with plaque formation. Conclusions Aged, smoking history, high LDL were significantly associated with carotid IMT of H-type hypertension patients. Aged, overweight, high LDL had significant effect on the progression of plaque formation.

Abstract:Aim To investigate the occurrence and risk factors of aortic valve calcification in patients with pneumoconiosis. Methods 194 cases with pneumoconiosis were selected as the research objects. According to the results of color Doppler echocardiography, they were divided into calcification group and non-calcification group. Another 200 healthy persons with normal physical examination during the same period were selected as the control group. To observe the occurrence of aortic valve calcification in patients with pneumoconiosis and healthy persons, firstly, sex, age, body mass index (BMI), smoking history, hypertension history, diabetes history, heart rate, blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), very low density lipoprotein cholesterol (VLDLC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), lipoprotein a (Lp(a)) were analyzed by single factor analysis between the two groups, and then, with or without aortic valve calcification as dependent variable, multivariate Logistic regression analysis was made on the single factor with statistical significance between the two groups of pneumoconiosis patients. Results Among 194 patients with pneumoconiosis, the incidence of aortic valve calcification was 20.10%. Among 200 healthy people, the incidence of aortic valve calcification was 12.00%. The incidence of aortic valve calcification in pneumoconiosis patients was significantly higher than that in healthy people (P<0.05). There were significant differences in age, history of hypertension, systolic blood pressure, FBG, TC and TG among pneumoconiosis patients (P<0.05). Further Logistic regression analysis showed that age (OR=2.6,5%CI 1.448～3.639), systolic blood pressure (OR=3.9,5%CI 1.871～6.433), and TG (OR=3.2,5%CI 1.699～6.146) were independent risk factors for aortic valve calcification in patients with pneumoconiosis. Conclusion In patients with pneumoconiosis, the incidence of aortic valve calcification is higher, and age, systolic pressure and TG are independent risk factors for aortic valve calcification in patients with pneumoconiosis, and monitoring the above indicators can provide predictive value for the occurrence of aortic valve calcification in patients with pneumoconiosis.

Abstract:Aim To investigate the correlation between serum soluble programmed cell death-1 (sPD-1) and carotid atherosclerosis (CAS) plaque in patients with type 2 diabetes mellitus (T2DM). Methods 87 patients with T2DM were selected as the study subjects, and 33 cases with normal glucose tolerance were selected as the control group.According to the presence or absence of CAS plaque, T2DM patients were divided into two groups:40 cases in T2DM without CAS group and 47 cases in T2DM with CAS group. Serum sPD-1 concentration and biochemical parameters were detected and compared in each group. The correlation between sPD-1 and each index was analyzed. ROC curve was used to analyze the predictive value of sPD-1 for T2DM with CAS plaque. Results The concentration of sPD-1 in T2DM without CAS group was significantly higher than that in control group (P＜0.05). The concentration of sPD-1 in T2DM with CAS group was significantly higher than that in control group and T2DM without CAS group (P＜0.05). SPD-1 was positively correlated with age, waist-hip ratio, triglyceride, fasting blood glucose, glycosylated hemoglobin A1, fasting insulin and high-sensitivity C-reactive protein (P＜0.05), negatively correlated with gender (male as reference), high density lipoprotein cholesterol and lipoprotein(a) (P＜0.05). ROC analysis indicated that the diagnostic value of sPD-1 in T2DM with CAS plaque formation was moderate (P＜0.05). Conclusion Serum sPD-1 may be involved in the formation and development of T2DM and atherosclerotic plaque, and it has predictive value for T2DM with CAS plaque formation.

Abstract:Aim To investigate the relationship between changes of beta 2-microglobulin (β2-MG) and in-stent restenosis in patients with coronary heart disease after PCI. Methods 162 patients with coronary heart disease treated by PCI were selected. Serum β2-MG levels were measured 12 hours before operation and 1 year after operation respectively. Coronary angiography was performed 1 year after PCI. The patients were divided into ISR group and control group according to the results of coronary angiography. Spearman correlation analysis was used to evaluate the correlation between β2-MG and Gensini integral and the number of coronary lesion branches. Gensini integral and the number of coronary lesion branches were used to evaluate the degree of coronary stenosis and to analyze the relationship between β2-MG and ISR. Results There was no significant difference in the number of coronary lesions, lesion location and lesion degree. Additionally, there was no significant difference in blood chemical change between the two groups 12 hours before operation and 1 month after operation(P>0.05). There was no significant difference in serum β2-MG between the ISI group and the control group before PCI (P>0.05). One month after PCI, the serum β2-MG of the two groups decreased, while it was higher in the ISI group than that of control group (P<0.05). There was no significant difference in the number, location and degree of coronary artery lesions between the two groups before PCI (P<0.05). Multivariate Logistic regression analysis showed that the incidence of ISR after PCI was correlated with the history of diabetes mellitus, difference of β2-MG between 12 hours before PCI and 1 month after PCI (P<0.05). Spearman correlation analysis showed that β2-MG was positively correlated with Gensini score (r=1.231, P=0.025), and the difference of β2-MG between 12 hours before PCI and 1 month after PCI was positively correlated with the number of coronary lesion branches (r=1626, P=0.014). The difference of β2-MG between 12 hours before PCI and 1 month after PCI was analyzed by ROC with ISR as the result variable. The cut-off value was 2.530 mg/L, the area under the ROC curve was 0.758, the standard error was 0.050, the Z value was 2.391, the sensitivity was 84.10%, and the specificity was 72.90%. Conclusions The serum β2-MG level in ISR group was significantly higher than that in non-stenosis group after PCI. The serum β2-MG level was positively correlated with restenosis after PCI, suggesting that β2-MG may be one of the risk factors for ISR after PCI.

Abstract:Aim To assess the prevalence of diabetes(DM) and associated factors among the elderly population aged 60~79 years in urban communities of Chengyu area. Methods A total of 2 135 adults aged 60~79 years were enrolled from urban communities of Chengdu and Chongqing area using a stratified cluster sampling method. Fasting blood glucose (FPG) was arranged in all patients. Oral glucose-tolerance test (OGTT) were used for assessments for those who have no history of DM. The survey was carried out by the same questionnaire for all subjects. Results DM prevalence was 39.6% in hypertensive patients aged 60 to 79 years in urban communities of Chengyu area, and with the rates of 35.0% and 42.9% in men and women, respectively (P＜0.01). DM prevalence of elderly hypertensive population increased with age (trend P=0.02). A total of 59.9% of the diabetic patients were newly diagnosed in this survey. Age, higher income level, family history of DM, overweight or obesity, Hypertriglyceridemia were risk factors of DM among hypertensive patients aged 60 to 79 years, and the physical exercise was protective factor. Conclusion There was a high prevalence of DM among hypertensive patients aged 60 to 79 in urban communities of Chengyu area, most diabetic patients were missed.

Abstract:Rapamycin is the most widely employed drug in drug-eluting stents. It has markedly reduced the risk of restenosis after coronary angioplasty. However, it caused late stent thrombosis through impairing the function of endothelial cells and delaying the re-endothelialization. Role of rapamycin in delaying re-endothelialization is complicated. This paper reviews the progress in research of the mechanism of suppressing the proliferation and migration of endothelial cells, attenuating the function of endothelial progenitor cells and inducing apoptosis of endothelial cells.

Abstract:Atherosclerosis is a progressive lesion of the intima of large and medium-sized arteries, which is the main cause of cardiovascular and cerebrovascular diseases. At present, the treatment of atherosclerosis is not satisfactory. Finding a new and more effective therapeutic target is a hot topic in current medicine. CD47, as a widely expressed protein, can promote the occurrence and development of atherosclerosis in many ways by binding to a ligand signaling regulatory protein alpha or platelet reactive protein-1, for example, blocking the efferocytosis of apoptotic cells, promoting the apoptosis of endothelial cells, inhibiting the physiological function of nitric oxide, and increasing the production of cell adhesion factors. Inhibition of CD47 expression can block these pathways and delay or even reverse atherosclerosis, so CD47 may become an important target for future anti-atherosclerosis studies.

Abstract:Atherosclerosis is one of the major causes of the high morbidity and mortality worldwide because of severe complications caused by vulnerable plaque rupture, such as myocardial infarction. With high resolution on soft tissue, magnetic resonance(MR)molecular imaging, combined with molecular contrast agents, may achieve plaque-targeted accurate imaging. Since the pathogenesis of atherosclerosis is more deeply investigated, and the synthetic technology is more advanced, there are more molecular contrast agents of great values for conversion. MR molecular imaging will provide evidence of diagnosis, classification and precision treatment for atherosclerosis. This essay reviewed recent advances in atherosclerotic MR molecular contrast agents.

Abstract:Endothelin-1 (ET-1) is a potent vasoconstrictor. It induces vascular contraction, stimulates proliferation of vascular smooth muscle cells and vascular remodeling in the pathogenesis of cardiovascular disease including pulmonary hypertension. Many studies have demonstrated that activation of mitogen-activated protein kinase (MAPK)/nuclear factor-kappaB (NF-κB) signal pathway induces up-regulation of endothelin receptors, and the up-regulation of endothelin receptors in pulmonary vascular smooth muscle cells results in pulmonary artery hypersensitivity and hyperresponsiveness to ET-1 with enhanced pulmonary vascular contraction, even spasm. This review article summarizes the roles of endothelin-1 and its receptors in the pathogenesis of pulmonary hypertension with focusing on the relationships between the up-regulation of endothelin receptors and pulmonary hypersensitivity and hyperresponsiveness, as well as down-regulation of endothelin receptors by inhibiting MAPK/NF-κB signal pathway. The inhibition of the endothelin receptor up-regulation in pulmonary artery improves pulmonary hypersensitivity and hyperresponsiveness to ET-1, and thus may provide a new strategy and novel therapeutic targets for the treatment of pulmonary hypertension.