Abstract:Cardiovascular disease is a serious threat to human life and health with accounting for more than 40% of the disease deaths in China, and its incidence has a tendency to rise. Therefore, it is important to develop new technologies and methods for the diagnosis and treatment of cardiovascular diseases. Nanotechnology is a novel discipline developed in this century, and it has brought new ideas and new methods together with the modern medicine, which established nanomedicine for the diagnosis and treatment of cardiovascular diseases, and with unique methods, it has already achieved a great significance in cardiovascular researches. This review focuses on recent advances in nanomedicine for the diagnosis and treatment of cardiovascular diseases.

Abstract:Aim To study the function of TRPC1/STIM1 in Ca²＋ entry and nitric oxide (NO) generation mediated by store-operated calcium channel (SOCC) and receptor-operated calcium channel (ROCC) in human umbilical vein endothelial cells. Methods Human umbilical vein endothelial cells were collected and cultured to the second~third passage. The constructed TRPC1 and STIM1 interference plasmids were transfected into human umbilical vein endothelial cells respectively, and the transfection efficiency was observed. The expressions of TRPC1 and STIM1 mRNA and protein were detected by real-time PCR and Western blot. The cells were incubated with CaR agonist spermine, CaR negative allosteric modulator Calhex231 and ROCC analogue TPA, protein kinase C (PKC) inhibitor Ro31-8220, PKCs and PKCμ inhibitor Go6967. Intracellular Ca²⁺ concentration ([Ca²⁺]_i) was detected using the fluorescence Ca²⁺ indicator Fura-2/AM, the production of NO was determined by DAF-FM of every group in HUVEC. The constructed TRPC1 and STIM1 interference plasmids were simultaneously transfected with human umbilical vein endothelial cells and incubated with CaR agonists to detect[Ca²＋]_i and NO production, and the interaction between STIM1 and TRPC1 was examined by co-immunoprecipitation. Results Compared with the control group, the expression of TRPC1 and STIM1 mRNA and protein in TRPC1 transfection group and STIM1 transfection group decreased obviously (P＜0.05). In four different treatment under the action of factors, the[Ca²＋]_i and the net NO fluorescence intensity ratio values of TRPC1 transfection group and STIM1 transfection group were significantly reduced (P＜0.05). Compared with control group, TRPC1 transfection group and STIM1 transfection group, the[Ca²＋]_i and the net NO fluorescence intensity ratio values of co-transfection group were significantly reduced (P＜0.05). TRPC1 and STIM1 interact to form a complex, and in the stimulation of CaR agonists under enhanced interaction. Conclusion TRPC1, STIM1 are components of SOCC and ROCC in Ca²＋ entry and NO generation in human umbilical vein endothelial cells.

Abstract:Aim To study the effect of irisin on the process of atherosclerosis in apolipoprotein E knockout (ApoE－/－) mice. Methods ApoE－/－ mice were randomly divided into three groups:normol group, atherosclerosis model group and irisin group, each group contained 10 mice. ApoE－/－ mice in normol group were fed with normal diet and saline, ApoE－/－ mice in atherosclerosis model group were fed with high fat diet and saline, ApoE－/－ mice in irisin group were fed with high fat diet and irisin, all mice were fed for 12 weeks. Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), the serum levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by chemical method, HE staining and total oil red O staining were used to analyze the size of aortic atherosclerotic plaque area, the mRNA and protein level of CD36, NF-κB p65, SOD were detected by real-time quantitative PCR (qPCR) and Western blot. Results The area of aortic plaque in atherosclerosis model group was significantly higher than that in normal group, the area of aorta plaque in irisin group was significantly lower than that in atherosclerosis model group. Compared with normal group, body weight of mice, TC, TG, LDLC, MDA, the expression of NF-κB p65 and CD36 mRNA and protein in atherosclerosis model group increased, while the activity of serum SOD and HDLC levels decreased (P＜0.05). Compared with atherosclerosis model group, body weight of mice, TC, TG, LDLC, MDA, the expression of NF-κB p65 and CD36 mRNA and protein in irisin group decreased, while the activity of serum SOD and HDLC levels increased (P＜0.05). Conclusion Irisin can reduce the occurrence and development of atherosclerosis in ApoE－/－ mice, which may be related to its decreasing body weight and blood lipid, inhibition of inflammation and anti-oxidative stress.

Abstract:Aim To explore a disintergrin and metalloproteinase 17 (ADAM17) regulating the protective effect of calcitonin gene-related peptide (CGRP) against proliferation of vascular smooth muscle cell (VSMC) and its mechanism.Methods The rat thoracic aortic smooth muscle cell line (A10VSMC) was used as the object of study. RNA interference was adopted to reduce ADAM17 expression. Western blot and real-time quantitative PCR were used to detect the expression levels of protein and mRNA. Methylthiazolyldiphenyl-tetrazolium bromide assay was used to evaluate cell viability of VSMC.Results CGRP could markedly attenuate angiotensin Ⅱ-induced VSMC proliferation. There were significant increases in expression levels of ADAM17 protein and mRNA in VSMC stimulated with angiotensin Ⅱ for 24 hours. Pretreatment with CGRP for 30 minutes significantly reduced the expression levels of ADAM17 protein and mRNA, whereas the effects could be reversed by CGRP receptor antagonist CGRP8-37. The results of RNA interference showed that ADAM17 siRNA significantly inhibitted angiotensin Ⅱ-mediated VSMC proliferation. Conclusion The reduction of ADAM17 expression may be the mechanism by which CGRP inhibits angiotensin Ⅱ-mediated VSMC proliferation.

Abstract:Aim To observe the effect of aerobic exercise and Lycium ruthenicum murr(LRM) polysaccharides on chronic cerebral ischemia and the differential expression of Notch channel related factors in brain and blood tissue. Methods 50 male KM mice were used to construct the model of chronic cerebral ischemia. They were randomly divided into model group (M group), and the intervention group including SW group, LRM group, LRM + SW group, positive control group (BLDJ group). The mice in the intervention group were treated with moderate intensity aerobic exercise and / or Lycium ruthenicum Murr polysaccharides (200 mg / kg). False surgery group (SO group). Neurobehavioral assessment was performed in each group; Nissl staining was used for brain tissue microstructure morphological observation; immunohistochemistry was used to detect the protein expression level of related factors. Real-time fluorescence quantitative technique was used to detect the expression of Notch pathway-related factors in brain tissue and blood. Results Brain tissue injury score was M group＞ SW group＞ LRM group＞ BLDJ group＞ LRM + SW group＞ SO group (P<0.05). Braintissue neuronal structure of M group had a large area of injury,LRM + SW group had the best effect (P<0.01). The expression of Notch1, Jagged1, NCX1 and SYP in the SO group was the highest, the positive expression in the intervention group was higher than that in the M group (P<0.01, P<0.05). The positive expression of LRM + SW group was higher than that of LRM group (P<0. 01). The intervention group regulating the expression of nerve cell repair related factors in tissues and blood was significantly higher than the M group (P< 0. 01), and the LRM + SW group had the highest level of expression. Notch1, Jagged1, NCX1 are positively correlated with tissue and blood, and the expression in the tissue is higher than the expression in the blood (P< 0. 05). Conclusion Aerobic exercise and Lycium ruthenicum Murr polysaccharides have a significant reduction in brain damage caused by chronic brain ischemia in mice,which can promote neuronal repair to varying degrees,and the combined effect between the two is more significant.Its role may be through the regulation of Notch channel related nerve repair factor expression, thereby inhibiting brain injury.

Abstract:Aim To explore the effects of intermittent alkaline stimulation on vascular ring calcification from the thoracic aorta of rats induced by high phosphorus and the possible mechanism. Methods Aortic rings were isolated from rat thoracic aorta and cultured in vitro, and randomly divided into three groups:control group, high phosphorus group (containing 10 mmol/L β-glycerol phosphate medium) and intermittent alkaline stimulation group (adjusting pH to 7.7 on the basis of high phosphorus medium). After 14 days of intervention, the expressions of L-type calcium channels (LTCC) β₃ subunit, runt-related transcription factor 2 (Runx2) and smooth muscle protein 22α (SM22α) were detected by immunohistochemical method. The degree of vascular ring calcification was detected by silver nitrate staining and calcium content test. Results Compared with control group, calcium content, the expressions of Runx2 and LTCCβ₃ were significantly increased in high phosphorus group (P＜0.001). Compared with high phosphorus group, calcium content, the expressions of Runx2 and LTCCβ₃ were significantly increased in intermittent alkaline stimulation group (P＜0.001). At the same time, the number of brown and black calcified nodules in high phosphorus group was higher than that in control group, and the number of brown and black calcified nodules in intermittent alkaline stimulation group was higher than that in high phosphorus group. Compared with control group, the expression of SM22α was significantly decreased in high phosphorus group (P＜0.001). Compared with high phosphorus group, the expression of SM22α was significantly decreased in intermittent alkaline stimulation group (P＜0.001). Correlation analysis showed that the expression of LTCCβ₃ was positively correlated with Runx2 protein expression (r＝0.704, P＝0.002) and negatively correlated with SM22α protein expression (r＝－0.670, P＝0.006). Conclusion Intermittent alkaline stimulation can promote high phosphorus induced vascular ring calcification from the thoracic aorta of rats. Its mechanism may be upregulation of LTCCβ₃ protein expression, enhancing the transformation of vascular smooth muscle cells into osteogenesis/chondrogenesis phenotype, and then promoting the occurrence of vascular ring calcification.

Abstract:Aim To study the effects of Xin Tong-tai (XTT) on serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and interleukin 6 (IL-6), and aortic tissue high-sensitivity C-reactive protein (hs-CRP) and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) in atherosclerotic rabbits. Methods A total of 120 healthy Japanese rabbits were randomly divided into control group, model group, low-dose XTT group, middle-dose XTT group, high-dose XTT group and rosuvastatin group. In this prospective study, the drug intervention groups were treated with the corresponding drugs at the same time. After 60 days, serum levels of Lp-PLA2 and IL-6 were measured; The contents of hs-CRP and LOX-1 in thoracic aorta were detected by immunohistochemistry method. Results The serum levels of Lp-PLA2 and IL-6 in low-dose XTT group, middle-dose XTT group and high-dose XTT group were lower than those in model group (P＜0.01). Compared with low-dose XTT group, the serum levels of Lp-PLA2 and IL-6 were decreased in middle-dose XTT group, high-dose XTT group and rosuvastatin group (P＜0.01 or P＜0.05). The expression levels of hs-CRP and LOX-1 in middle-dose XTT group and high-dose XTT group were lower than those in model group (P＜0.01). Compared with low-dose XTT group, the expression levels of hs-CRP and LOX-1 were decreased in middle-dose XTT group, high-dose XTT group and rosuvastatin group (P＜0.05). Immunohistochemical staining showed that in model group, there was a large amount of hs-CRP and LOX-1 expression in aortic intima; Compared with model group, the expressions of hs-CRP and LOX-1 in the aorta were reduced in low-dose XTT group, middle-dose XTT group, high-dose XTT group and rosuvastatin group. Conclusion Xin Tong-tai can decrease the levels of Lp-PLA2, IL-6, hs-CRP and LOX-1 in atherosclerotic rabbits, so as to achieve the effect of reducing atherosclerosis inflammatory reaction.

Abstract:Aim To screen out the specific expression of miRNA in ISR, and its significance was analyzed by bioinformatics method. Methods The expression profiles of miRNA in ISR patients were screened by miRNA gene chip to screen out ISR related miRNA. The relative expression of miRNA and ISR was verfied by Real-time PCR. miRNA target genes were predicted by bioinformatics, and data mining of the downstream target genes of miRNA was carried out, and the ISR related miRNA-Gene-Network was constructed, the possible mechanism of ISR was discussed. Results The difference expression of miRNA in ISR patients was detected by high throughput miRNA microarray, 43 genes were down regulated and 10 genes were up-regulated. Bioinformatics and Real-time PCR were used to verfy the result of microarray. A number of miRNA and target genes related to ISR were obtained, and the regulatory networks of miRNA and target genes were constructed miRNA-Gene-Network. Quantitative detection of Real-time PCR quantitative detection showed that miR-126 in group ISR was significantly lower than that in group non-ISR (0.507±0.131 vs. 1.427±0.337, P＜0.05). Conclusion The expression of miRNA in ISR patients is different from no-ISR, these miRNA and target genes may be related to the occurrence of ISR, the decrease of miR-126 level tended to occur in ISR.

Abstract:Aim To investigate the prevalence and risk factors of coronary artery calcification in low-dose CT screening population for lung cancer. Methods A total of 2722 asymptomatic men over 40 years of age was selected, who were screened first time for lung cancer with low-dose CT from 2013 to 2016, aged 40-81 years old, including 1052 smokers and 1670 non-smokers. The related medical history and blood biochemical examination data were collected, including age, body mass index, smoking history, diabetes history and blood glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), serum uric acid and creatinine. Visual scoring method was used to assess coronary artery calcification score. The difference of calcification detection rate among different populations was examined by χ² test. Coronary artery calcification and risk factors were analyzed by Spearman correlation analysis and multivariate Logistic regression. Results Among the 2722 cases, coronary artery calcification occurred in 642 cases (23.6%), of which mild, moderate and severe calcification accounted for 88.8%, 8.9% and 2.3%, respectively, with an average age of 56.7±9.8 years; There were 2080 cases without coronary artery calcification, with an average age of 49.5±7.1 years. The detection rate of coronary artery calcification in smoking group was higher than that in non-smoking group (25.9% vs 22.2%, P＝0.027). Coronary artery calcification was significantly related to age, smoking, hyperlipidemia, diabetes mellitus, and high serum creatinine, but was not significantly related to HDLC, LDLC, and high serum uric acid. With the increase of age, the detection rate of calcification increased gradually. The detection rate of calcification in smoking group was 2 times higher than that in non-smoking group under 50 years old. Conclusion The detection rate of mild coronary artery calcification is higher in low-dose CT screening asymptomatic population for lung cancer. Age, smoking, hyperlipidemia, diabetes and high serum creatinine are risk factors for coronary artery calcification.

Abstract:Aim To observe the expression of miR-4463 in the plasma and tissues of patients with arteriosclerosis obliterans of lower limbs (ASO). Methods miRNA microarray method was used to screen the differentially expressed miRNA in the plasma of three ASO patients and three controls. Real time PCR technique was carried out to verify the expression level of miR-4463 in the plasma and tissues of 50 patients with ASO and 50 healthy controls, and the relationship of clinical stage with miR-4463 level was analyzed. Target gene prediction software was used to predict target genes of miR-4463, and then the function and signaling pathways of predicted target genes were analyzed by Gene Ontology and KEGG pathway. Results Compared with the controls, 51 miRNAs changed in the plasma of patients with ASO more than 1.5 times (P<0.05). The expression of miR-4463 in plasma and vascular intimal tissues of ASO patients was significantly decreased, and decreased gradually with Fontaine stage. Bioinformatics analysis revealed that the target genes of miR-4463 were related to cell polarity, migration, lipid metabolism and endocytosis. Conclusion miR-4463 is involved in the pathogenesis of ASO, and decreased miR-4463 level may indicate the occurrence of ASO.

Abstract:Aim To investigate the correlation between the level of serum creatinine (Cr), serum cystatin C(CysC), glomerular filtration rate (GFR) and in-stent restenosis after coronary artery drug eluting stent implantation. Methods A retrospective analysis of 624 cases of patients were performed coronary drug eluting stents and coronary angiography in Shengjing Hospital of China Medical University, according to the review of coronary angiography results, patients were divided into in-stent restenosis group (147 cases) and non in-stent restenosis group (477 cases), which clinical data, biochemical indicators, interventional target vessels and restenosis data were analysed. Results Both before and after the PCI operation and follow-up coronary angiography, serum creatinine levels, serum cystatin C were higher in in-stent restenosis group than those in non in-stent stenosis group patients (P<0.05); glomerular filtration rate was significantly lower than that in non in-stent restenosis group (P<0.05); Multivariate COX regression analysis showed that elevated serum creatinine levels, serum cystatin C, decline of glomerular filtration rate were the independent risk factors for in-stent restenosis in drug eluting stents. Conclusion The level of renal function is closely related to the occurrence of in-stent restenosis. The increase of serum creatinine, serum cystatin C and decrease of glomerular filtration rate are the independent risk factors for in-stent restenosis in drug eluting stents.

Abstract:Aim To explore the relationship between high density lipoprotein (HDL) particle, low density lipoprotein (LDL) particle and coronary artery lesions in premenopausal and postmenopausal female patients with coronary artery disease. Methods Data were collected from 79 female patients with coronary artery disease diagnosed by coronary angiography. According to whether menopause, the patients were divided into premenopausal group (n＝37) and postmenopausal group (n＝42). HDL particles and LDL particles were detected and analyzed by Lipoprint lipoprotein analyzer.The relationship between two lipoprotein particles and severity of coronary artery lesions was studied. Results Compared with the premenopausal group, large particle HDL concentration (102.6±45.2 mg/L vs 143.8±49.7 mg/L, P＜0.05) and its proportion (23.34%±8.26% vs 31.15%±7.98%, P＜0.05), and mean diameter of LDL particles (259.5±8.1 vs 265.7±3.7, P＜0.05) were decreased, small particle HDL concentration (124.0±76.8 mg/L vs 87.0±34.9 mg/L, P＜0.05) and its proportion (27.26%±12.34% vs 18.62%±6.53%, P＜0.05),Bü type proportion in LDL (73.8% vs 48.6%, P＜0.05), and Gensini score (50.88±26.46 vs 30.43±18.54, P＜0.05) were increased, in the postmenopausal group. In premenopausal group and postmenopausal group, large particle HDL concentration and the average diameter of LDL particles in patients with multivessel lesions were lower than those in patients with single vessel lesions, and the Gensini score was higher than that in patients with single vessel lesions. Large particle HDL concentration and the average diameter of LDL particles in postmenopausal group were lower than those in premenopausal group, and small particle HDL proportion and Gensini score in postmenopausal group were higher than those in premenopausal group. LDL particle size and large particle HDL concentration were negatively correlated with the Gensini score in the premenopausal group and the postmenopausal group. Conclusion Compared with the premenopausal group, large particle HDL concentration is lower, small particle HDL concentration is higher, the average diameter of LDL particle is smaller, and the degree of coronary artery lesions is more serious in the postmenopausal group. Large particle HDL concentration and the mean diameter of LDL are significantly correlated with the severity of coronary artery lesions.

Abstract:Aim To investigate the relationship among helicobacter pylori (Hp) infection with blood lipid level and AIP in patients with high risk of stroke, and to provide new ideas for the treatment of dyslipidemia and atherosclerosis. Methods Three hundred and sevety-one patients with high risk of stroke were screened from 2872 people who were consecutively selected and had health examination from June 2014 to January 2015 in the Department of Medical Center, General Hospital of Wanbei Coal and Electricity Group. Their clinical information was collected. The Hp infection status was detected by the 14C urea breath test and the serum oxidized low density lipoprotein (ox-LDL) levels was determined by enzyme linked immunesorb-ent assay (ELISA). The relationship between Hp infection and total cholesterol (TG), triglyceride (TG), low density lipoprotein (LDLC), high density lipoprotein (HDLC), ox-LDL, AIP were analyzed. Results 155 patients(41.8%, 155/371)were found infected by Hp；the levels of TC, TG, LDLC, ox-LDL and AIP in Hp infection group were significantly higher than those in non HP infection group, the difference was statistically significant (P＜0.05). Multiple linear regression analysis showed that Hp infection was positively correlated with the level of AIP. Conclusion Hp infection may induce the disorder of lipid metabolism in high risk population of cerebral apoplexy, which leads to the increase of AIP level, and promotes the development of atherosclerosis.

Abstract:Aim To investigate the distribution and histopathological features of cerebral artery stenosis in patients with abnormal serum immunoglobulin E(IgE) and unknown etiology. Methods From March 2013 to October 5,5 cases of serum-immunoglobulin E level in young ischemic stroke adults with unknown etiology of abnormal IgE in our hospital were prospectively collected. The patients were divided into IgE normal group(18 cases)and IgE abnormal group (17 cases)according to the level of IgE. It observed inflammatory cells infiltration and mast cells by HE staining and toluidine blue staining respectively and determined the expressions of matrix metalloproteinase-9(MMP-9), monocyte chemotaxis protein-1 (MCP-1) and serum IgE by immunohistochemistry. Results The number of cerebral artery stenosis was 31 in the IgE normal group, and it was 36 in the IgE abnormal group. The distribution of stenosis showed that the narrow lesions of two groups was concentrated in the middle cerebral artery and internal carotid artery. There were 3 cases with outer membrane inflammatory cell infiltration(16.67%) in the IgE normal group, and it was 11 cases (64.71%) in the IgE abnormal group. There was significant difference between the two groups (P=0.004). Compared with IgE normal group, the mean optical density of MMP-9 and MCP-1 in IgE abnormal group were higher(P=0.4,0.02). Conclusion Abnormal serum-immunoglobulin E level in young ischemic stroke adults with unknown etiology should focus on the possible presence of inflammatory vascular disease.

Abstract:Aortic dissection (AD) is a high-risk vascular disease, and more and more scholars pay attention to the research of its pathogenesis, prevention and treatment. At present, the animal models of AD can be divided into in vivo models and in vitro models. In vivo models include mechanical modeling, chemical induced modeling and genetic engineering modeling. In vitro model is to simulate the formation of AD in vitro. In this paper, the research progress of AD model is reviewed.

Abstract:Venous thromboembolism is a common and frequently occurring disease. Inferior vena cava (IVC) filter is a device designed to avoid pulmonary embolism(PE). There has been a long history for its development. With being widely used nowadays, recyclable filters become the direction. This article will briefly summarize the characteristics of various filters.

Abstract:Recently, clinicians pay more attention to coronary microcirculation dysfunction, and a series of evaluation indexes for microcirculation appeared. However, there is not much research on the treatment of coronary microcirculation dysfunction. The symptoms of ischemic heart disease of women are more obvious than that of men. But it's more difficult to detect obstructive coronary artery disease (CAD) in women. The prognosis in patients with coronary microcirculation dysfunction is worse in women. This review reviews the diagnosis, treatment and prognosis progress of coronary microcirculation dysfunction, especially the sex differences in incidence and prognosis.

Abstract:Genetic researches of atrial fibrillation (AF) include the following topics which are important in clinical practice:①the molecular genetic variations of mono/polygenic AF; ②the reasonable classification of AF based on genetics; ③the underlying genetic reasons of its familial segregation; ④the impact of genotype difference on prognosis of patients with AF and AF risk prediction; ⑤the genetic studies on AF treatment. This review is an update on the above-mentioned issues.

Abstract:Effects of aerobic exercise on anti inflammation, regulation of blood lipid metabolism and balance immunity can stabilize and reduce atherosclerotic plaque (As), which becomes an important measure for the treatment of acute coronary syndrome (ACS). It is urgent to explore and study the mechanism because aerobic exercise can reduce the risk of ACS and prevent the occurrence of ACS. This paper reviews the possible mechanism, role and progress of aerobic exercise in reducing As formation.