Abstract:Vascular calcification is an active biological process similar to bone and cartilage formation with multiple regulatory factors involved in. At present, the main clinical treatment strategy for vascular calcification is still limited to mechanical therapy. However, with the progress of research, there have been more and more attempts and explorations for targeted interventions for vascular calcification, including chemical drugs such as phosphate binders, pyrophosphates and bisphosphonates, thiosulfates and targeted intervention in OPG/RANK/RANKL signaling, osteoclasts, etc. However, these intervention strategies have different degrees of defects and development bottlenecks. How to effectively dissolve and absorb hydroxyapatite crystals and amorphous calcium deposits, reverse the progression of vascular wall calcification phenotype and return to normal, and fully take into account the bi-directional balance of bone-vessel axis, is still tough work ahead and a long way to go.

Abstract:Aim To investigate the role of exosomes in the calcification of mouse vascular smooth muscle cells (VSMCs) induced by CD137 signal. Methods The mouse thoracic aorta VSMCs were performed by patch-attaching method, and VSMCs were divided into two groups:the control group, the CD137 excitation group. The exosomes were extracted by kit and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Fluorescence microscopy was used to observe VSMCs uptake of exosomes. Lentiviral vector of nuclear factor of active T cell c1 (sh-NFATc1) was constructed and infected with VSMCs. The experiments were divided into three groups:control group with exosomes treatment, CD137 excitation group with exosomes treatment, silenced NFATc1＋CD137 excitation group with exosomes treatment. Western blot was used to detect the expressions of α-smooth muscle actin (α-SMA), bone morphogenic protein 2 (BMP-2) and Runt-related transcription factor 2 (Runx-2). Calcium salt deposition in VSMCs was detected by Von Kossa staining. Results Western blot results showed that microvesicles in both groups expressed exosomes surface marker proteins CD9 and CD81. Under electron microscopy, the exosomes were round and cup-shaped, and its diameter was about 30-100 nm. The expression of NFATc1 protein increased significantly in exosomes of CD137 excitation group. Compared with the control group exosomes treatment group, the expressions of calcification-related indicators BMP-2 and Runx-2 proteins increased significantly in CD137 excitation group with exosomes treatment, while the expression of α-SMA decreased significantly. Compared with CD137 excitation group with exosomes treatment, the expressions of BMP-2 and Runx-2 proteins decreased significantly in silenced NFATc1＋CD137 excitation group with exosomes treatment, while the expression of α-SMA increased significantly. Von Kossa staining showed that VSMCs calcium deposits in CD137 excitation group with exosomes treatment were more than those in control group with exosomes treatment, while those in silenced NFATc1＋CD137 excitation group with exosomes treatment were significantly lower than those in CD137 excitation group with exosomes treatment. Conclusion CD137 signal pathway mediates VSMCs calcification through exosome transmitting NFATc1.

Abstract:Aim To elucidate effect of rosiglitazone (RSG) on calcification induced by advanced glycation end-products (AGE) in vivo on rat. Methods A rat model of diabetic arterial calcification (DM+VDN) was induced by streptozotocin (STZ) and high fat diet, as well as vitamin D3 and nicotine, then divided into three groups:untreated group, group treated with RSG, group treated with glibenclamide (GLB). Metabolic parameters, aortic calcium content, malondialdehyde (MDA) content, Cu/Zn superoxide dismutase (SOD) activity, receptor for advanced glycation end products (RAGE) and plasma AGE levels were measured. Results DM+VDN exhibited enhanced levels of AGE, as well as high levels of MDA and SOD. Aortas from DM+VDN exhibited high levels of calcium content. This calcification was also dramatically increased, as shown by von Kossa staining. In aorta, strong immunostaining for RAGE were observed in DM+VDN. Conversely, rosiglitazone attenuated these changes in calcium accumulation and the investigated proteins in aortas, as well as plasma AGE, MDA and SOD. Conclusion The results suggest that rosiglitazone might exert anti-calcification in partly through down-regulation of RAGE expression, thus limiting the cells’ susceptibility toward oxidative stress induced by AGE.

Abstract:Aim To investigate the effect of peroxisome proliferators activated receptorγ (PPARγ) on the calcification of rat aortic vascular smooth muscle cells (VSMC) induced by transforming growth factor-β1 (TGF-β1). Methods Rat aortic vascular smooth muscle cells were cultured in vitro and divided into normal control group and different concentrations of TGF-β1 group (1 μg/L, 2 μg/L, 4 μg/L, 8 μg/L). Then they were divided into normal control group, calcification group (TGF-β1 4 μg/L), rosiglitazone group (RSG, 20 μmol/L), and calcification+rosiglitazone (RSG, 20 μmol/L) group. The effects of agonist RSG on calcification of VSMC, calcium content and alkaline phosphatase (ALP) activity were detected in the cells, alizarin red S staining was used to detect the formation of calcified nodules, and Western blot was used to detect vascular smooth muscle cells marker α-smooth muscle actin (α-SMA), PPARγ, protein expression of osteoblast-like marker Runt-related transcription factor (Runx2). Results Compared with the normal control group, calcium deposition and ALP activity of VSMC treated with TGF-β1 were significantly increased (P<0.05), and the effect was most obvious when TGF-β1 concentration was 4 μg/L. And Runx2 expression of osteoblast-like cell was significantly increased (P<0.05), while α-SMA expression of smooth muscle cell markers was decreased (P<0.05). Whereas calcium sulfate deposition and ALP activity of VSMC were significantly decreased (P<0.05), α-SMA and PPARγ expression was significantly increased after RSG was added(P<0.05), on the contrary, Runx2 expression was significantly inhibited (P<0.05). Conclusion TGF-β1 can induce differentiation and calcification of VSMC into osteoblast-like cells, and TGF-β1-induced calcification of VSMC can be inhibited by PPARγ agonist RSG.

Abstract:Coronary artery calcification is a common pathological feature in many diseases, such as coronary atherosclerosis, diabetic angiopathy and chronic kidney disease. Statins are commonly used in patients with coronary atherosclerotic heart disease and dyslipidemia. Previous studies have shown that statins may inhibit coronary artery calcification, but recent studies have suggested the opposite. In view of the disputes over the relationship between statins and coronary artery calcification, this article analyzes the mechanism of coronary artery calcification, the relationship between statins and coronary artery calcification, and the reasons of contradiction between them.

Abstract:Hypoxia inducible factor-1α (HIF-1α) is a highly specific nuclear transcription factor produced by cells in hypoxic environment, which plays an important role in the bone formation and bone regeneration. Vascular calcification is a complex biological process similar to bone formation and actively regulated. It is a major risk factor for increased cardiovascular mortality, but its mechanism has not been fully elucidated. Recent studies have shown that HIF-1α may be involved in vascular calcification through the mechanism such as osteogenic differentiation of vascular smooth muscle cells (VSMC), glycometabolism pathway, inflammation and Notch signaling pathway. This paper reviews the relationship between HIF-1α and vascular calcification.

Abstract:Aim To explore the effect and mechanism of astaxanthin on cerebral infarction rats based on AMPK/eNOS/NF-kappa B signal pathway. Methods The rat model of cerebral infarction was established by modified Longa method. 50 successful modeling SD male rats were randomly divided into model control group, positive control group, astaxanthin low, medium and high dose group, with 10 rats in each group, and 10 rats without model as blank control group. The blank control group and the model control group were given the same volume of normal saline, the positive control group was given 20 mg/(kg·d) nimodipine, and the astaxanthin low, medium and high dose groups were given 0,0, 30 mg/(kg·d) astaxanthin, respectively, for 14 consecutive days. Neurological changes were detected in rats; cerebral infarction area was measured by triphenyl tetrazolium chloride staining; levels of interleukin-10 (IL-10), interleukin-1β, interleukin-6 and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay; cell apoptosis in ischemic penumbra of cerebral cortex was detected by TUNEL; the expressions of adenosine monophosphate activated protein kinase (AMPK), endothelial nitric oxide synthase (eNOS) and nuclear factor κB (NF-κB) mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR); the protein expressions of p-AMPK, AMPK, p-eNOS, eNOS and NF-κB were detected by Western blot. Results Astaxanthin could significantly improve neurological function and cerebral infarction area in rats with cerebral infarction (P＜0.01), inhibit the expression of pro-inflammatory factors IL-1β, IL-6 and TNF-α, promote the expression of anti-inflammatory factor IL-10 (P＜0.05), reduce the cell apoptosis rate of cortical ischemic penumbra (P＜0.01), down-regulate the expressions of NF-κB mRNA and protein, and promote phosphorylation of AMPK and eNOS (P＜0.05), but there was no significant difference in the expressions of AMPK, eNOS mRNA and protein (P＞0.05). Conclusion Astaxanthin can significantly improve neurological function, cerebral infarction area, cell apoptotic rate of cortical ischemic penumbra and serum cytokines in rats with cerebral infarction, and its mechanism may be closely related to AMPK/eNOS/NF-κB signal pathway.

Abstract:Aim To study the effect of renal artery radiofrequency ablation in endarterium or adventitia on renal artery atherosclerosis by detecting expression levels of renal artery macrophage scavenger receptor (CD36 and SR-A). Methods 14 healthy beagles (7 male, 7 female) were randomly divided into experimental group (n=10) and control group (n=4), and two arteries in every beagle of the experimental group were randomly assigned to endarterium group(10 artery) and adventitial group(10 artery). At 1 month and 3 months follow-up, renal artery angiography was performed to observe the renal artery morphological change; HE staining and immunohistochemical staining were used to observe the renal artery pathological change; Western blot was used to detect the expression levels of renal artery macrophage scavenger receptor (CD36 and SR-A). Results (1) At 1 month follow-up, 1 case of obvious renal artery stenosis was found in endarterium group. (2) In the experimental group after renal denervation, intimal structure of renal artery was discontinued by HE staining, but no change was found in the control group; Immunohistochemistry showed the higher expression of CD36 in renal artery of experimental group. (3) The expression of scavenger receptors (CD36 and SR-A) in renal artery:①At 1 month follow-up, the expression levels of scavenger receptor CD36 and SR-A were significantly higher in endarterium group (n=5) and adventitia group (n=5) than that in the control group (n=4) (P<0.001); And the expression levels of scavenger receptor CD36 and SR-A were significantly higher in endarterium group (n=5) than that in adventitia group (P=0.040 and P=0.007); ②At 3 months follow-up, the expression levels of scavenger receptor CD36 and SR-A were significantly higher in endarterium group (n=5) and adventitia group (n=5) than that in control group (n=4) (P<0.001); And the expression levels of scavenger receptor CD36 and SR-A were significantly higher in endarterium group (n=5) than that in adventitia group (n=5) (P<0.001). Conclusion Renal artery stenosis may appear after renal denervation, and it was easier to lead to renal artery stenosis after renal denervation in endarterium;The structure of renal artery endarterium may be damaged (thickening and discontinuous) after renal denervation; and it is higher in endarterium, so it has the potential risk of renal atherosclerosis after renal denervation.

Abstract:Aim To study the effect of aerobic exercise on memory ability of mice with vascular dementia. Methods To expose the bilateral common carotid arteries of KM mouse, repeatedly occlusion of common carotid artery and blood letting in caudal vein were made to establish a mouse model of vascular dementia. The mice were randomly divided into three groups:sham group, model group, and aerobic exercise group. Aerobic exercise began on the second day after operation for 7 weeks. Behavioral tests were performed after the training. Brain tissue samples (hippocampus, prefrontal lobe, whole brain and serum) were collected 30 days after the operation. The pathological changes of hippocampal CA1 region were observed by HE staining. The apoptosis of hippocampal CA1 region was detected by TUNEL method. Western blot and ultraviolet spectrophotometer were used to detect the expression of Bcl-2, Bax, malondialdehyde (MDA), superoxide dismutase (SOD), growth-related protein-43 (GAP-43), brain-derived neurotrophic factor (BDNF), acetylcholine synthase (ACHE), acetylcholine transferase (CHAT), synaptophysin (SYP), nerve cell adhesion molecule (NCAM) and nerve cell adhesion molecule receptor 2B (NR2B). Results Compared with the sham group, the time of fear memory in the model group was significantly shortened. The neuronal cells in the hippocampus of the model group were severely damaged and the number of apoptotic cells was increased, the expression of MDA and ACHE protein was significantly increased, the levels of synaptophysin, NCAM, NR2B, SOD, BDNF, CHAT, GAP-43 and Bcl-2 protein expression decreased, Bax protein expression did not change significantly. Compared with the model group, the time of fear memory in the aerobic exercise group was significantly prolonged, the histopathological changes in the hippocampus of the brain were improved, the number of apoptotic cells was decreased, the expression of MDA and ACHE protein was significantly decreased, and the levels of synaptophysin, NCAM, NR2B, SOD, BDNF, CHAT, GAP-43 and Bcl-2 protein expression increased, while Bax protein expression did not change significantly. Conclusion Aerobic training may improve the learning and memory function of vascular dementia mice by up-regulating the expression of Bcl-2, SOD, BDNF, CHAT, GAP-43, SYP, NCAM and NR2B, down-regulating the expression of MDA and ACHE, reducing the damage of free radicals and apoptosis of hippocampal neurons.

Abstract:Aim To investigate whether homocysteine (Hcy) upregulates the expression of tumor necrosis factor α(TNF-α) and interleukin-6 (IL-6) by inducing activation of nuclear factor kappa B (NF-κB) pathway by miR-33, promotes inflammatory lesions and exacerbates atherosclerosis (As). Methods RAW264.7-derived macrophages were induced by oxidized low-density lipoprotein (ox-LDL) as foam cells, and miR-33 mimics/miR-33 inhibitors were transfected into cells. Each group received 5.0 mmol/L of Hcy intervention; oil red “O” staining was used to determine whether the foam cell model was successfully induced; Western blot and real-time quantitative PCR was used to determine the protein and mRNA expression of NF-κB, TNF-α, IL-6; the cellular cholesterol content was analyzed by HPLC. Results The successfully induced foam cells were stained with oil red “O”, and the nuclei containing lipid droplets were stained red; compared with other group, the expression of NF-κB, TNF-α and IL-6 protein and mRNA, the intracellular cholesterol content was significantly increased in the miR-33 mimics group (P＜0.05). No difference was observed in the above indexes between blank group, miR-33 mimics-NC group and miR-33 inhibitor-NC group (P>0.05). Conclusion Hcy can upregulate the expression of TNF-α and IL-6 by inducing miR-33 to activate NF-κB pathway, increase inflammatory reaction and promote atherosclerosis (As).

Abstract:Aim To investigate the effect and its mechanism of 8-O-acetyl-SM on acute myocardial infarction rats based on p38 MAPK-CRYAB pathway. Methods A rat model of acute myocardial infarction was established by ligation of the left anterior descending coronary artery. Fifty male SD rats were randomly divided into model control group, positive control group, 8-O-acetyl-SM low, medium and high dose groups, with 10 rats in each group. In addition, 10 rats were used as blank control groups. The blank control group and the model control group were given the same volume of normal saline, the positive control group was given aspirin enteric-coated tablets (100mg/(kg·d)), and the 8-O-acetyl-SM low, medium and high dose groups were given 0,0 and 30 mg/(kg·d) 8-O-acetyl-SM, continuous administration for 14 days. The changes of cardiac function were detected, HE staining was used to observe the pathological changes of myocardium in rats, TUNEL was used to detect the apoptosis of myocardial cells, ELISA was used to detect the levels of SOD, LDH, GSH-Px and MDA, RT-PCR was used to detect the mRNA expression of Bcl-2, Bax and Caspase-3, Western blot was used to detect the expression of p-p38 MAPK/p38 MAPK and p-CRYAB/CRYAB. Results 8-O-acetyl-SM significantly could improve cardiac function and pathological changes of myocardial tissue in rats with acute myocardial infarction (P＜0.05), reduce myocardial apoptosis rate (P＜0.05), reduce oxidative stress damage (P＜0.05), up-regulate the expression of Bcl-2, down-regulate the expression of Bax and Caspase-3 (P＜0.05), promote phosphorylation of p38 MAPK and CRYAB (P＜0.05), but there was no significant change in the expression of p38 MAPK and CRYAB protein among the groups (P＞0.05). Conclusion 8-O-acetyl-SM can significantly improve myocardial injury symptoms, up-regulate Bcl-2 expression, down-regulate Bax and Caspase-3 expression, promote p38 MAPK and CRYAB phosphorylation, and its mechanism may be related to p38 MAPK-CRYAB pathway.

Abstract:Aim To discuss the effect and mechanism of diallyl trisulfide on coronary microembolization (CME) in rats based on the TLR4/MyD88/NF-κB signaling pathway. Methods Sixty SD rats were randomly divided into blank control group, model group, positive control group, low, medium and high dose groups of diallyl trisulfide, 10 rats in each group. The blank control group and model group were given the same volume of normal saline, the positive control group was given rosuvastatin (3.0 mg/(kg·d)), and the diallyl trisulfide low, medium and high dose groups were given diallyl trisulfide (0,0, 40 mg/(kg·d)). After 14 days of pretreatment, CME models were established in the model group, the positive control group, the diallyl trisulfide low, middle and high dose groups by injecting 42 μm microembolic balls into the left ventricle, and the blank control group was injected the same volume of normal saline into the left ventricle. The changes of cardiac function were detected, the area of myocardial microinfarction was detected by HBFP staining, the apoptosis of myocardial cells was detected by TUNEL, the content of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by ELISA, electrochemical method was used to detect troponin I (cTnI) and creatine kinase isoenzyme (CK-MB), the mRNA expressions of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor κB p65 (NF-κB p65) were detected by RT-PCR, Western blot was used to detect the protein expression of TLR4, MyD88 and NF-κB p65 in rat myocardium. Results Diallyl trisulfide can significantly improve the cardiac function of CME rats, significantly reduce the area of myocardial microinfarction and the apoptotic rate of myocardial cells, effectively inhibit the expression of inflammatory factors IL-1β, TNF-α and myocardial injury indicators cTnI, CK-MB, and significantly reduce the relative expression of TLR4, MyD88 and NF-κB p65 mRNA and protein. Conclusion Diallyl trisulfide can inhibit cardiac dysfunction and myocardial injury in CME rats, and its mechanism may be closely related to TLR4/MyD88/NF-κB signaling pathway.

Abstract:Aim To investigate the impact of helicobacter pylori (HP) infection and cytotoxin associated protein A toxin of HP (HP-CagA) on serum matrix metalloproteinase-9 (MMP-9) in patients with coronary heart disease (CHD), and the relationship between HP-CagA and coronary lesion. Methods 105 patients with CHD were chosen in this trial, including 35 patients with acute myocardial infarction (AMI), 35 patients with unstable angina pectoris (UAP) and stable angina pectoris (SAP), while 35 inpatients with normal coronary artery (NCA) in the same period. The level of serum MMP-9, the positive rate of HP-IgG antibody and HP-CagA-IgG antibody were measured by enzyme-linked immunosorbent assay (ELISA) and the correlation between the level of serum MMP-9, the positive rate of HP-IgG antibody, the positive rate of HP-CagA-IgG antibody and coronary angiography Gensini score were analyzed respectively. The differences between CHD patients with HP infection and without HP infection were compared, and the differences between CHD patients with positive HP-CagA-IgG and negative HP-CagA-IgG were compared. Results The four groups showed significant differences in serum MMP-9 level (all P＜0.05), among them, AMI group＞UAP group＞SAP group＞NCA group (all P＜0.05). Compared to NCA group, AMI group, UAP group and SAP group were higher in Gensini score (all P＜0.05). There was significant correlation between serum MMP-9 level and Gensini score in each group (all P＜0.05). The positive rates of HP-IgG in SAP group, UA group, AMI group and NCA group were 40%, 57.1%, 74.3% and 28.6%, respectively; among them, AMI group＞UAP group＞SAP group＞NCA group (all P＜0.05); the patients with positive HP-IgG in each group showed the higher levels of MMP-9 than those with negative HP-IgG (all P＜0.05); there was significant correlation between the positive rate of serum HP-IgG and Gensini score in each group (all P＜0.05). The positive rates of HP-CagA-IgG in SAP group, UAP group, AMI group and NCA group were 17.1%, 31.4%, 40.0% and 11.4%, respectively; among them, AMI group＞UAP group＞SAP group＞NCA group (all P＜0.05); the patients with positive HP-CagA-IgG in each group showed the higher levels of MMP-9 than those with negative HP-CagA-IgG, there were statistical differences (all P＜0.05); there was significant correlation between the positive rate of serum HP-CagA-IgG and Gensini score in each group (all P＜0.05). The serum MMP-9 level among each group, HP-IgG(＋)CagA-IgG(＋) subgroup＞HP-IgG(＋)CagA-IgG(－) subgroup＞HP-IgG(－)CagA-IgG(＋) subgroup (all P＜0.05); the positive rate of serum HP-IgG and the positive rate of serum HP-CagA-IgG were significantly correlated with the serum MMP-9 level and Gensini score, especially the positive rate of serum HP-CagA-IgG was more closely related to the serum MMP-9 level and Gensini score (all P＜0.05). Conclusion HP infection especially HP-CagA infection, might be related to the occurrence and development of CHD through the large secretion of MMP-9 by endothelial cells, which might be new indicators of the severity of the coronary artery in future.

Abstract:Aim To investigate the serum level of cluster of differentiation 137 (CD137) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and evaluate its prognostic value in patients with NSTE-ACS.Methods 122 hospitalized patients were divided into two groups:NSTE-ACS group (n＝93) and control group (n＝29).According to GRACE score, NSTE-ACS group was divided into three subgroups:low-risk group, medium-risk group and high-risk group. Cardiac troponin I (cTnI), brain natriuretic peptide (BNP) and other biochemical indicators were measured in each group. The serum level of CD137 was determined by enzyme-linked immunosorbent assay. Major adverse cardiac events (MACE) were followed up for 1 year in all patients. Receiver operating characteristic curve (ROC) was used to evaluate the value of serum CD137 level in mid-term prognosis of NSTE-ACS patients. Results Compared with the control group, the serum CD137 level increased significantly in each subgroup of NSTE-ACS group (P＜0.01). Among the subgroups of NSTE-ACS group, the serum CD137 level in high-risk group was significantly higher than that in low-risk group and medium-risk group (P＜0.05). Serum CD137 level was positively correlated with GRACE score (r＝0.867, P＜0.01), and it was also positively correlated with cTnI and BNP levels (r value was 0.942 and 0.945, respectively, both P＜0.01). The incidence of MACE in NSTE-ACS group was significantly higher than that in control group in one year (P＜0.01), and serum CD137 level was positively correlated with the incidence of MACE (r＝0.324, P＜0.01). The area under the ROC curve of CD137 predicting mid-term MACE in NSTE-ACS patients was 0.847 (95%CI 0.718-0.918, P＜0.01), and the sensitivity and specificity were 80.0% and 79.4% respectively. Conclusion Detection of serum CD137 level is helpful for risk stratification of patients with NSTE-ACS and has certain clinical value for prognosis judgement of patients with NSTE-ACS.

Abstract:Aim To explore the correlation between plasma lipoprotein associated phospholipase A2 (Lp-PLA2), lipoprotein(a)[Lp(a)] and the progression of acute stage and vascular stenosis in patients with large atherosclerotic cerebral infarction. Methods 117 patients with large atherosclerotic cerebral infarction were collected, including 67 patients with non-progressive cerebral infarction (NPCI), and 50 patients with progressive cerebral infarction (PCI). According to head and neck CT angiography (CTA), magnetic resonance angiography (MRA) or digital subtraction angiography (DSA), the patients were divided into moderate stenosis group (48 cases), severe stenosis group (40 cases) and occlusion group (29 cases). The level of Lp-PLA2 and Lp(a) were measured and the differences among different groups were compared, and the correlation with the progression of cerebral infarction and the stenosis of the vessels was analyzed.Results There was no significant difference in gender, age, hypertension, coronary heart disease, smoking and drinking between PCI group and NPCI group (P＞0.05), and the levels of diabetes and low density lipoprotein cholesterol (LDLC) were higher than those in NPCI group (P＜0.05). The levels of Lp-PLA2 and Lp(a) in PCI group were significantly higher than those in NPCI group (P＜0.05 or P＜0.01). Compared with moderate stenosis group, the levels of Lp-PLA2 and Lp(a) in severe stenosis group and occlusion group were significantly increased (P＜0.05 or P＜0.01). And compared with the severe stenosis group, the levels of Lp-PLA2 and Lp(a) in occlusion group were significantly increased (P＜0.05). Spearman correlation analysis showed that Lp-PLA2 and Lp(a) levels were positively correlated with the degree of vascular stenosis in the head and neck (P＜0.05 or P＜0.01). Conclusion Lp-PLA2 and Lp(a) levels are closely related to the progression of cerebral infarction with large vascular atherosclerosis and the degree of vascular stenosis in the head and neck.

Abstract:Aim To investigate the relationship between neutrophil/lymphocyte ratio (NLR) and the blood flow status of infarct related artery (IRA) in patients with acute myocardial infarction (AMI) before and after primary percutaneous coronary intervention (PPCI). Methods 598 patients with AMI (including STEMI and NSTEMI) treated with PPCI were divided into three groups according to the blood flow status of IRA before and after PPCI:group A:the blood flow of IRA before PPCI was TIMI Ⅲ grade; group B:the blood flow of IRA was TIMI 0～Ⅱ grade before PPCI, and TIMI Ⅲ grade after PPCI; group C:the blood flow of IRA was TIMI 0～Ⅱ grade before PPCI and after PPCI. At the same time, NLR and related clinical parameters were detected and Logistic regression analysis was performed. Results There were significant differences in high sensitivity C-reactive protein (hs-CRP), NLR, cardiac troponin T(cTnT) and left ventricular ejection fraction (LVEF) among the three groups. In group A, the values of hs-CRP, NLR and cTnT were the lowest, and LVEF was the highest. In group C, the values of hs-CRP, NLR and cTnT were the highest, while LVEF was the lowest, and the Killip classification≥2 was more common. The mortality was the highest in group C. Multivariate Logistic regression analysis showed that NLR was independently correlated with the blood flow status of IRA, high NLR predicted a higher incidence of TIMI 0～Ⅱ grade in IRA blood flow before and after PPCI. Conclusions NLR is a strong and independent predictor of blood flow status of IRA. High NLR indicates a worse prognosis in AMI patients, which is useful for early risk stratification in patients with AMI undergoing PPCI.

Abstract:Atherosclerosis (As) is the main pathological factor of cardiovascular and cerebrovascular diseases. The pathological mechanism of the development of atherosclerosis has not been fully elucidated so far. Autophagy is a highly biological process in eukaryotic cells. Normal levels of autophagy inhibit the development of atherosclerosis, and autophagy defects or excessive autophagy accelerate plaque rupture, which lead to the occurrence of cerebrovascular accidents. Studies have shown that microRNA affects As processes by participating in the regulation of autophagy in As-related cells. This article reviews the role of microRNA in the regulation of autophagy levels in endothelial cells, macrophages, and smooth muscle cells in As.

Abstract:Too high level of plasma phytosterols can increase the risk of arteriosclerotic cardiovascular disease. Because of the mutation of ATP binding cassette transporter G5/G8, the level of phytosterol in the blood circulation of patients with phytosterolemia is 30-100 times higher than that of normal people, and they will suffer from atherosclerosis at an early age. Besides, phytosterolemia usually has diseases of the blood system, so it is necessary to take proper treatment intervention as soon as possible. Patients with phytosterolemia also have very high levels of low density lipoprotein cholesterol and multisite xanthoma in early childhood, so attention should be paid to differential diagnosis. Dietary control and ezetimibe are effective ways to treat phytosteroidemia.

Abstract:Apolipoprotein CⅢ (ApoCⅢ) not only participates in the occurrence and development of atherosclerosis cardiovascular diseases(ASCVD) through lipid metabolism disorders, but also has been recognized as an independent factor of inflammatory and atherosclerosis. Clinical studies have found that ApoCⅢ was linked with cardiovascular disease(CVD), and its cellular effects related with CVD are also confirmed in basic research. Fortunately, in addition to traditional therapeutic strategies, such as lifestyle changes and lipid-lowering drug treatments, antisense oligonucleotides specifically targeting ApoCⅢ mRNA have opened the door to a new era of reducing ApoCⅢ and the treatment of CVD. Therefore, this paper summarizes the clinical significance of ApoCⅢ and the future treatment direction.