Abstract:Aim To observe whether the Wnt/β-catenin signaling pathway mediates the protective effect of Shenmai injection (SM) on cerebral ischemia-reperfusion injury (CIRI) in rats. Methods According to the randomized block principle, 84 SD rats were divided into 7 groups:sham operation group (sham), model group (MCAO), SM＋model group (SM＋MCAO), normal saline (NS)＋model group (NS＋MCAO), phosphate buffered solution (PBS)＋SM＋model group (PBS＋SM＋MCAO), Wnt/β-catenin antagonist dickkopf-1 (Dkk-1)＋SM＋model group (Dkk-1＋SM＋MCAO), Dkk-1＋model group (Dkk-1＋MCAO), 12 rats in each group. Rat CIRI model was established by middle cerebral artery occlusion (MCAO) with line embolus. Immediately after cerebral ischemia, SM＋MCAO group, PBS＋SM＋MCAO group and Dkk-1＋SM＋MCAO group were intraperitoneally injected with SM (15 mL/kg), whereas NS＋MCAO group was injected with equal amount of NS. At 30 min before the model was set up, Dkk-1＋SM＋MCAO group and Dkk-1＋MCAO group were injected with Dkk-1 (1 g/L, 1 μL) to the ventricle, whereas PBS＋SM＋MCAO group was injected with equal amount of PBS. After reperfusion for 24 h, neurobehavioral score was assessed in each group, cerebral infarction volume was measured, expressions of Bcl-2, Bax and β-catenin protein were detected in the semi-dark zone of cerebral infarction, and Bcl-2/Bax ratio was calculated. Results Compared with the sham group, neurobehavioral score, cerebral infarction volume, and the expressions of Bcl-2, Bax, and β-catenin proteins were increased in the MCAO group (P＜0.05), and Bcl-2/Bax ratio was reduced (P＜0.05). Compared with the MCAO group, neurobehavioral score, cerebral infarction volume and Bax protein expression were significantly reduced in the SM＋MCAO group (P＜0.05), the expressions of Bcl-2 and βcatenin proteins and Bcl-2/Bax ratio were significantly increased (P＜0.05). Compared with the SM＋MCAO group, neurobehavioral score, cerebral infarction volume and Bax protein expression were significantly increased in the Dkk-1＋SM＋MCAO group (P＜0.05), while Bcl-2 protein expression and Bcl-2/Bax ratio were significantly decreased (P＜0.05). Conclusion Shenmai injection improves brain damage of CIRI rat by up-regulation of Wnt/β-catenin signaling pathway.

Abstract:Aim To explore the mechanism of adipophilin regulating neutral cholesterol ester hydrolase (nCEH) expression thus mediating lipid accumulation in RAW264.7 macrophages. Methods The constructed retroviral plasmid vectors with adipophilin of no expression and over expression were transfected into package cell PA317, then collected virus solution was used to infect RAW264.7 macrophages by screening and identifying to obtain RAW264.7 cell lines with adipophilin stably silenced and highly expressed. The mRNA and protein expression levels of nCEH were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. High performance liquid chromatography (HPLC) was taken to detect the contents of intracellular cholesterol ester. Results The cholesterol and cholesterol ester levels were significantly higher in adipophilin over-expression group than in the control group (P<0.01), while dramatically lower than that in the control group when adipophilin was supressed (P<0.01). In addition, adipophilin inhibited nCEH expression. Furthermore, in RAW264.7 macrophages with high adipophilin expression, treatment with 100 nmol/L protein kinase Cδ agonist PMA for 30 min resulted in remarkable reductions of nCEH mRNA and protein expression(P<0.05), on the contrary, treatment with 100 nmol/L PKCδ inhibitor Rottlerin for 30 min increased the expression of nCEH(P<0.05). Conclusion Adipophilin may exert influence over lipid accumulation by inhibiting the expression of nCEH in RAW264.7 macrophages, and PKCδ played an important role in this regulatory mechanism.

Abstract:Aim To investigate the effect of low shear stress (LSS) on the expression of Bmi-1 in human umbilical vein endothelial cells (HUVEC) and its possible mechanism. Methods Human umbilical vein endothelial cells were cultured in vitro. Immunofluorescence was used to detect the localization of Bmi-1 in the cells. 0.5 h, 1 h, 2 h and 4 h were loaded into human umbilical vein endothelial cells by parallel plate flow chamber system. The expression of Bmi-1 mRNA was detected by real-time quantitative RT-PCR. The expression of Bmi-1 protein was detected by Western blot.Specific signal inhibitor SB2219 was used to investigate the signal transduction pathway. Results Immunofluorescence observation showed that Bmi-1 was mainly distributed in the nucleus of human umbilical vein endothelial cells. The expression of Bmi-1 was significantly increased after 0.5 h of LSS, the expression of Bmi-1 mRNA and protein decreased gradually with the prolongation of the time (1 h, 2 h and 4 h); the shear stress could significantly activate phosphorylated p38 expression; SB2219 could significantly inhibit the expression of Bmi-1. Conclusion LSS can induce the expression of Bmi-1 in human umbilical vein endothelial cells, the expression of Bmi-1 is closely related to the length of stimulation, this effect may be regulated by p38 signal.

Abstract:Aim Based on the mTOR/ULK1 autophagy signaling pathway to discuss the mechanism of gypenoside improving aorta lipid deposition of ApoE－/－ mice. Methods 30 healthy ApoE－/－ mice were randomly divided into the model control group and the gypenoside group, and the simvastatin group, 10 mice in each group. 10 C57bL/6J mice were used as the normal control group. The model control group, the gypenoside group and the simvastatin group were fed with high-fat diet for 4 weeks. The gypenoside group and simvastatin group were treated with gypenoside 2.973 g/(kg·d) and simvastatin 2.275 mg/(kg·d) by gastrogavage for 8 weeks, respectively. The normal control group and the model control group were given by gastrogavage with the normal saline of the same volume. The formation of atherosclerotic plaque of the mice was detected by HE staining, and the blood lipid level was detected by the fully automatic biochemical analyser. The expressions of ULK1, Beclin1, LC3 and p-mTOR proteins were dectected by the Western blot.Results Compared with normal control group, in the model control group, TG, TC and LDLC were significantly increased (P＜0.05), HDLC was significantly decreased (P＜0.05), large atheromatous plaques could be seen in aortic canal, ULK1, Beclin1 and LC3 were significantly decreased (P＜0.01), p-mTOR was significantly increased (P＜0.01). Compared with the model control group, in the gypenoside group and the simvastatin group, TG, TC and LDLC were significantly decreased (P＜0.05), HDLC was significantly increased (P＜0.05), atheromatous plaques in aortic canal were significantly decreased, ULK1, Beclin1 and LC3 were significantly increased (P＜0.01), p-mTOR was significantly decreased (P＜0.01 or P＜0.05). Conclusion Gypenosides could relieve the formation of atherosclerotic plaques and prevent atherosclerosis possibly through regulating the autophagy.

Abstract:Aim To investigate the protective effect of resveratrol (RSV) on myocardial ischemia/reperfusion (MI/R) injury in diabetic rats and its mechanism. Methods Type 2 diabetic rat model was induced by intraperitoneal injection of streptozotocin. After 2 weeks, diabetic rats were randomly divided into sham operation (sham) group, MI/R group and resveratrol (RSV) group. MI/R injury model was induced by ligation of the left anterior descending coronary artery. Lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (cTnI), myocardial infarction area, cardiac systolic and diastolic function were measured in each group. Myocardial cell apoptosis index was detected by TUNEL assay. Western blot was used to detect the expressions of silent information regulator of transcription 1 (SIRT1), p53, acetylated p53 (Acetyl-p53), Bcl-2, Bax, and cytosolic and mitochondrial cytochrome C (Cyt C) and apoptosis inducing factor (AIF). HE staining was used to detect myocardial injury score. Results Compared with the sham group, myocardial infarction area, myocardial injury score, the expressions of myocardial LDH, CK, cTnI, Acetyl-p53, Bax, cytosolic Cyt C and AIF, and myocardial cell apoptosis index were significantly increased, while cardiac systolic and diastolic function were significantly decreased, expressions of Bcl-2, SIRT1, mitochondrial Cyt C and AIF were significantly reduced, in the MI/R group. Compared with the MI/R group, myocardial infarction area, myocardial injury score, the expressions of myocardial LDH, CK, cTnI, Acetyl-p53, Bax, cytosolic Cyt C and AIF, and myocardial cell apoptosis index were significantly decreased, while cardiac systolic and diastolic function were significantly improved, expressions of Bcl-2, SIRT1, mitochondrial Cyt C and AIF were significantly increased, in the RSV group. There was no difference of p53 expression in the three groups. Conclusion Resveratrol can attenuate MI/R injury by anti-apoptosis in diabetic rats, and its mechanism is related to SIRT1/p53 signaling pathway.

Abstract:Aim To explore the effect of sorting receptor Sortilin on lipid metabolism in THP-1 macrophages. Methods THP-1 macrophages were incubated with oxidized low density lipoprotein (ox-LDL). Change of Sortilin expression in lipid-loaded THP-1 macrophages were detected by Western blot. Under the overexpression and silence of Sortilin in THP-1 macrophages, intracellular cholesterol efflux was measured by liquid scintillation counting apparatus, intracellular lipid content was detected by high performance liquid chromatography, and the situation of intracellular lipid droplets was observed by oil red O staining. Results The expression of Sortilin in THP-1 macrophages was increased in the manners of dose- and time-dependence of ox-LDL. The expression level of Sortilin in THP-1 macrophages reached the peak after 24 hours treatment with 50 mg/L ox-LDL. Compared with the control group, after Sortilin overexpression, the cholesterol efflux of macrophages was decreased, the intracellular lipid content was increased, and the lipid droplets was increased significantly, while Sortilin was silent, it just happened to be the opposite. Conclusion Sortilin inhibits the cholesterol efflux of macrophages and promotes the accumulation of intracellular lipid.

Abstract:Aim To investigate the inhibitory effect of berberine on the proliferation of human umbilical vein endothelial cell (HUVEC) induced by oxidized low density lipoprotein (ox-LDL) and the changes of related signaling pathways. Methods HUVEC was cultured in vitro, and the proliferation of HUVEC was stimulated by ox-LDL and intervened with berberine at different concentrations. The inhibitory effect of berberine on proliferation of HUVEC was detected by cell counting kit 8 and EdU incorporation experiment. The expressions of related genes and proteins and the changes of signaling pathway were analyzed by real-time quantitative PCR and Western blot. Results In a concentration dependent manner, berberine (1~50 mg/L) significantly inhibited the HUVEC proliferation induced by ox-LDL, and reduced the expressions of proliferating cell nuclear antigen (PCNA), nuclear factor κB (NF-κB) and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). These effects were associated with decreased phosphorylation levels of PI3K/Akt, ERK1/2 and p38MAPK signaling pathways. Conclusion Berberine inhibits the proliferation of HUVEC induced by ox-LDL through the down-regulation of PCNA, NF-κB and LOX-1 expressions. PI3K/Akt, ERK1/2 and p38MAPK signaling pathways are involved in this process.

Abstract:Aim To explore the effect of lysine methyltransferase SET8 on proliferation and migration of rat vascular smooth muscle cells (VSMC). Methods Vascular smooth muscle cells were obtained from rat thoracic aorta, and then randomly divided into control group, empty plasmid group and SET8-shRNA group. The expression of SET8, E-cadherin was detected by RT-PCR and Western blot, cell proliferation was measured by MTT assay, cell migration was measured by transwell asssy. Results The expression of SET8 in SET8-shRNA group was lower than that in normal control group and empty plasmid group (P＜0.05). MTT results showed that the proliferation activity of 12 h, 24 h, 36 h and 48 h in SET8-shRNA group was significantly lower than that in normal control group and empty plasmid group (P＜0.05). The Transwell assay showed that the cell migration ability in SET8-shRNA group was decreased (P＜0.05). The expression of E-cadherin mRNA and protein in SET8-shRNA group was significantly higher than that in normal control group and empty plasmid group (P＜0.05). Conclusion Interference with SET8 gene expression could promote the expression of E-cadherin and inhibit the proliferation and migration of rat vascular smooth muscle cells.

Abstract:Aim RNA interference was used to downregulate angiotensin converting enzyme (ACE) and angiotensinⅡtype 1 receptor (AT1R), and to observe its effects on blood pressure and brain tissue injury in spontaneously hypertensive rats (SHR). Methods SHR was randomly divided into 5 groups:blank control group, virus control group, Ad5-ACE-shRNA treatment group, Ad5-AT1R-shRNA treatment group, Ad5-ACE-AT1R-shRNA treatment group, and WKY normal blood pressure control group was set up. All rats in each group were injected 1 time in the first and seventeenth day of the experiment. On the third day after the first injection, enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of ACE and Ang Ⅱ in rat brain, real-time fluorescent quantitative PCR was used to detect the expression of ACE mRNA and AT1R mRNA in brain tissue, Western blot was used to detect the expression of ACE and AT1R protein in brain tissue. At the end of the experiment, brain tissue was examined by light microscopy to observe the brain structure. Results On the third day after the first injection, the tail arterial pressure of Ad5-ACE-shRNA treatment group, Ad5-AT1R-shRNA treatment group and Ad5-ACE-AT1R-shRNA treatment group decreased by 25.2±5.3 mmHg, 23.5±4.8 mmHg and 27.1±6.4 mmHg, 24.4±5.6 mmHg, 23.6±4.9 mmHg and 26.3±6.9 mmHg respectively on the 14th day, and the blood pressure rose on the 17th day after Ad5-ACE-shRNA treatment and Ad5-AT1R-shRNA treatment after the second injection The tail arterial pressure of Ad5-ACE-AT1R-shRNA treatment group decreased again. On the 23rd day, the arterial pressure decreased by 40.2±4.5 mmHg, 37.8±3.9 mmHg and 43.7±7.3 mmHg respectively before the first injection. On the 37th day, The blood pressure rose to the level before the second injection on the 40th day. The blood pressure of the blank control group and the virus control group continued to increase by 26 mmHg, there was no significant difference between the two groups; the tail arterial pressure of the normal blood pressure control group had no obvious change. The expression of ACE mRNA in brain tissue of Ad5-ACE-shRNA treatment group and Ad5-ACE-AT1R-shRNA treatment group and the expression of AT1R mRNA in the brain tissue of Ad5-AT1R-shRNA treatment group and Ad5-ACE-AT1R-shRNA treatment group were significantly lower than those of blank control group and virus control group (P＜0.05), but there was no significant difference compared with normal blood pressure control group. The expression of AT1R protein in brain tissue of Ad5-ACE-shRNA treatment group, Ad5-AT1R-shRNA treatment group and Ad5-ACE-AT1R-shRNA treatment group was significantly lower than that of blank control group and virus control group (P＜0.05). The light microscope showed that the brain tissue structure of Ad5-ACE-shRNA treatment group, Ad5-AT1R-shRNA treatment group and Ad5-ACE-AT1R-shRNA treatment group was significantly improved.Conclusion RNA interference downregulated ACE and AT1R expression, reduced blood pressure in spontaneously hypertensive rats and improved brain injury, especially Ad5-ACE-AT1R-shRNA treatment had obvious effect and less side effect. RNA interference has a good application prospect for gene therapy of hypertension.

Abstract:Aim To explore association of epicardial adipose tissue (EAT) with coronary artery calcification and chemerin in maintenance hemodialysis (MHD) patients. Methods 90 MHD patients in Tianjin Fifth Central Hospital were included in the study. MHD patients were divided into low-risk (＜10% ), mid-risk (10%~20%) and high-risk group (＞20%) according to Framingham risk score (FRS). 60 normal subjects were selected as control group. Serum chemerin, C-reactive protein (CRP), blood routine and biochemistry were determined, multi-slice spinal CT examination were underwent. The EAT volume and coronary artery calcium score (CACS) were calculated with the Philips workstation. The relationship of EAT volume with CACS, serum chemerin, CRP, FRS were analyzed. Results Serum chemerin, CRP and neutrophil to lymphocyte ratio were significantly higher in MHD group compared to control group (all P＜0.01). EAT volume, CACS and serum chemerin were significantly higher in high-risk group and in mid-risk group compared to those in low-risk group (P＜0.05 or P＜0.01), EAT volume, serum chemerin were significantly higher in high-risk group compared to those in mid-risk group (all P＜0.05). The multivariate linear stepwise regression showed that CACS, serum chemerin, CRP, FRS were the influencing factors of EAT(P＜0.05 or P＜0.01). ConclusionSerum chemerin, CRP and neutrophil to lymphocyte ratio were significantly higher in MHD patients. There was microinflammation in MHD patients. In MHD patients, EAT volume, CACS and serum chemerin in high-risk group and in mid-risk group were both higher than those in low-risk group. CACS, serum chemerin, FRS were correlated with EAT volume.EAT might be used as predictors of cardiovascular risk in MHD patients.

Abstract:Aim To assess the biomechanical characteristics of carotid isolated plaques using intima-media thickness (IMT) automatic tracking technique. Methods The study included 30 patients who had isolated plaques in carotid artery. IMT strain rate (SR), IMT time strain rate (TR) and AIIc% were measured by IMT automatic tracking technique along with acoustic densitometry (AD) to assess the variation of the IMT and acoustic density in the upstream, fibrous cap top and downstream regions of the plaque and ipsilateral normal carotid. All plaques were divided into three groups according to IMT:small group (1.2 mm2.5 mm). The differences of SR, TR and AIIc% were identified among three groups. Results SR and TR were significantly reduced in plaques group compared with controls. Compared with cap top area(CTA), the SR of upstream area (UA) were significantly increased. However, the SR, TR of downstream area (DA) were significantly lower than CTA and UA. Compared with control, the SR, TR were significantly reduced in CTA and DA. AIIc% in UA and CTA were significantly lower than DA. AIIc% in all three regions were significantly higher than that in control group. The SR, TR for the 3 plaque regions were negatively correlated with AIIc% (r=－0.63, r=－0.58, P<0.05). The SR, TR among three groups showed no statistical significance. Conclusion IMT automatic tracking along with AD could be applied to identify the anisotropic biomechanical features in carotid isolated plaques, which may be a new noninvasive way to early assess the biomechanical properties of carotid plaque.

Abstract:Aim To observe the changes of intraarterial oxidative stress markers in patients with type 2 diabetes mellitus (T2DM) combined with arteriosclerosis obliterans (ASO) before and after treatment of lower extremity arteries, and to investigate the effect of oxidative stress in patients with T2DM combined with ASO and the effect of interventional therapy on intraarterial oxidative stress markers. Methods Thirty patients with T2DM complicated with subendocardial artery (tibiofibular artery) who underwent interventional therapy were enrolled in the study. All patients underwent lower extremity digital subtraction angiography (DSA), some patients also underwent percutaneoius transluminal angioplasty (PTA). 14 patients were treated with DSA alone (control group), and 16 patients in DSA+PTA (treatment group). In the control group and the treatment group, routine examinations were performed before interventional operation, and venous blood was taken to measure blood lipid, hemoglobin A1c(HbA1c) and oxidative stress markers, including serum superoxide dismutase (SOD), and the lipid peroxides final product malondialdehyde (MDA). The control group and the treatment group were also required to take 3 mL of the arterial blood before the intervention. In addition, the arterial blood of the treatment group was taken before and after PTA in the same part of the distal artery of the ischemic artery. SOD, MDA levels were measured in the above samples. Results There was no obvious stenosis in the arteriography of the lower extremity in the control group. Preoperative SOD level in arterial and venous blood was lower in the treatment group than that in the control group, MDA level was higher than that in the control group(P＜0.05). There was no significant difference in the levels of SOD and MDA between venous blood and arterial blood before the intervention in the control group and the treatment group(P＞0.05). The SOD level of the treatment group was lower in the ischemic area before the intervention than that of the arterial blood(P＜0.05), but the MDA level was higher (P＜0.05). The SOD level of the treatment group were lower in the ischemic area after intervention than that of the ischemic area and the arterial blood before intervention(P＜0.05), but the MDA level was higher(P＜0.05). Conclusion The use of antioxidation stress drugs before and after intervention may improve the long-term prognosis of treatment and reduce the incidence of restenosis.

Abstract:Aim To study the effect of different dosages of ticagrelor on the efficacy and renal function in elderly (＞70 years) patients with acute coronary syndrome (ACS) combined with moderate chronic renal insufficiency (CRI). Methods 72 patients with ACS and CRI were randomly divided into full-dose group (36 cases) and half-dose group (36 cases). On the basis of routine treatment of the coronary heart disease and renal insufficiency, patients in full-dose group were treated with full-dose ticagrelor (loading dose 180 mg, followed by 90 mg/times, 2 times/day); patients in half-dose group were treated with half-dose ticagrelor (loading dose 90 mg, followed by 45 mg/times, 2 times/day). The platelet inhibition rate (PIR), serum creatinine (Scr) and alanine aminotransferase (ALT) were detected and the estimated glomerular filtration rate (eGFR) was calculated in the two groups before treatment, after treatment 1,3, 6,2 months, the ischemic events, bleeding events and drug adverse reaction were followed up after treatment within 12 months. ResultsAfter treatment for 1 months, 3 months, 6 months and 12 months, the PIR and Scr in the two groups had an increased trend and the eGFR had a decreased trend compared with before treatment. There was no significant difference in PIR between the two groups (F＝3.679, P＝0.059), Scr and ALT in the half-dose group was significantly lower than those in the full-dose group (F＝234.8,9.451, P＝0.0,0.000), eGFR in the half-dose group was significantly higher than that in the full-dose group (F＝54.521, P＝0.000). After 12 months of follow-up, there was no significant difference in the incidence of ischemic events between the two groups (χ²＝0.050, P＝0.824), incidence of bleeding events and incidence of dyspnea in the half-dose group were lower than those in the full-dose group (χ²＝5.8,5.030, P＝0.3,0.025). Conclusion For elderly patients with ACS and moderate renal insufficiency, there is no significant difference in PIR value between half-dose and full-dose of ticagrelor, but the effect of half-dose of ticagrelor on renal function and liver function is less, bleeding rate is low, and safety is better.

Abstract:Aim To investigate the influence of the intracranial collateral circulation on the short-term prognosis of symptomatic carotid artery stenosis after carotid artery stenting(CAS). Methods 111 patients with extracranial carotid artery stenosis were treated with stent in our hospital, the collateral circulation of patient and their rate of events at clinical end point during follow-up period were compared and analyzed. Results The patients in good collateral circulation group was 53, and in poor collateral circulation group was 58; Good collateralization was more frequently associated with serious ipsilateral ICA stenosis (≥90%), and was more obvious with the development of the anterior communicating artery (ACoA), leptomeningeal collaterals(LC)(P＜0.05) and had negative correlation with diabetes (P＝0.036); There were 2 patients with cerebral hemorrhage after CAS, and all of them were in good collateral circulation group; All patients were followed up for 1 year,and 3 cases of recurrent cerebral infarction were in poor collateral circulation group; The scores of NIHSS and mRS in good collateral circulation group were significantly lower than those of poor collateral circulation group before and after 1 year. Conclusion Good collateral circulation can improve the neurological function of symptomatic carotid stenosis patients, and may be a protective factor for ipsilateral stroke during clinical follow-up.

Abstract:Aim To investigate the manifestations of several common acute superior mesenteric artery events of multi-slice spiral CT angiography (MSCTA) in order to acknowledge the disease deeply. Methods The clinical and imaging data of 23 cases of acute superior mesenteric artery were reviewed and summarized. Results 9 of 23 cases were isolated superior mesenteric artery dissection(ISMAD),according to classification of YUN,the type Ⅰ(n=7) and the type Ⅱb(n=2),double-lumen sign and low-density intimal flap were seen in all cases. 3 of 23 cases were intramural haemorrhagic(IMH) with out-pouching ulcer crater. 11 of 23 cases were acute superior mesenteric arter thromboembolism(SMAT), the direct signs of which in CT images was filling defect in mesenteric vessels. Conclusion Although the clinical symptoms of ISMAD,IMH and SMAT are similar,but each with typical imaging findings on MSCTA ,which is accurate, fast and effective for the diagnosis of acute superior mesenteric artery events.

Abstract:Lipoprotein(a) is a high risk factor for the formation and progression of atherosclerosis, and high level of lipoprotein(a) has been confirmed as a predictor of coronary heart disease. Because it is mainly controlled by genetics, diet, exercise, lifestyle, traditional lipid-lowering drugs have little effect on lipoprotein(a) level. With the deepening research, the metabolism, pathogenesis and harm of lipoprotein(a) have been gradually understood. Oxidized modified lipoprotein(a) has a stronger atherogenic effect. New lipid lowering drugs that reduce lipoprotein(a) have been developed, each of them has different target, functional intensity and mechanism of action on lowering lipoprotein(a), and the effect on the prognosis of the disease remains to be observed. This paper reviews the research progress of lipoprotein(a) metabolism, genetic regulation, oxidative modification and clinical intervention.

Abstract:The accumulation of a large number of apoptotic and necrotic cells in atherosclerotic plaques is the main cause of plaque enlargement, necrotic core formation and plaque rupture. Apoptotic cells are engulfed and cleared quickly by macrophage and other phagocytes mediated efferocytosis in physiological state. However, recent studies have shown that the clearance rate of apoptotic cells in plaque is far lower than that in physiological state, and its mechanism is closely related to macrophage mediated efferocytosis dysfunction. This review summarizes the research progress of macrophage mediated efferocytosis and its functional defects in atherosclerosis, and hopes to provide theoretical and experimental basis for prevention and treatment of atherosclerotic cardiovascular disease.

Abstract:Cardiovascular diseases, such as myocardial infarction, chronic heart failure, are the main causes of human death. It is clear that lipid metabolic dysfunction, diabetes and so on are important risk factors for the occurrence and development of cardiovascular diseases. Changes in myocardial structure, Ca²＋ signaling, cellular metabolism, oxidative stress, activation of renin-angiotensin system and mitochondrial dysfunction are associated with the development of cardiovascular diseases. Since β₃-adrenoceptor (β₃-AR) has been cloned in 1989, the researchers have found that β₃-AR is associated with cardiovascular diseases. β₃-AR stimulation can regulate lipid metabolism, improve cardiac function and remodeling, therefore, perhaps prevent and treat cardiovascular diseases.

Abstract:As a chronic inflammatory disease of blood vessel, atherosclerosis(As)is the main cause of coronary heart disease, cerebral infarction and peripheral vascular disease, which seriously threatens the health and life of human beings. As a new type of anti-inflammatory molecules of the interleukin-1 family, interleukin-37 plays an important biological function in a variety of inflammatory diseases, neoplastic disease and autoimmune diseases. The anti-inflammatory effects of interleukin-37 may be related to interleukin-18 binding protein and Smad3. Clinical and animal experiments have confirmed that interleukin-37 is involved in the development of As and may annihilate the progression of As by inhibiting the functions of macrophages, mast cells and dendritic cells.