Abstract:This paper, from the perspective of small molecule drugs regulating reverse cholesterol transport mechanism, introduces the latest research progress in the role of RCT key proteins in the regulation of cholesterol efflux and lipid metabolism by small molecule drugs, and explore the role of small molecule drugs with different chemical structures in mediating the expression of different drug target proteins in RCT. The purpose of this study is, from a point of view of pharmacology, to provide a new thinking mode for RCT related research.

Abstract:The traditional physiology textbooks hold the opinion that arterial blood pressure gradually decreases as it moves away from heart, which we think is not precise saying. A large number of studies have shown that the arterial systolic pressure and pulse pressure will gradually increase during the pressure wave transmitting from aorta to the peripheral large arteries. This phenomenon can be explained by pulse wave reflection theory. This paper suggests that the relevant expressions in traditional textbooks should be corrected to make them more accurate, so as to avoid misleading medical students or clinicians. Pulse wave reflection has potential physiological and clinical significance, which should be paid more attention to.

Abstract:Aim To observe the expression of miR-155 in TNF-α-induced human umbilical vein endothelial cells and the impacts of miR-155 on TNF-α-induced human umbilical vein endothelial cells, and to investigate thoroughly the mechanisms of miR-155 modulating TNF-α-mediated human umbilical vein endothelial cell apoptosis. Methods Human umbilical vein endothelial cells were cultured in vitro and treated with different concentrations of TNF-α for different time. MTT assay was used to detect human umbilical vein endothelial cell activity. Human umbilical vein endothelial cell apoptosis was analysed by Hoechst33342 fluorescence staining and by Annexin-V FITC/PI double staining. The expression of miR-155 was detected by qRT-PCR, the potential apoptosis-related target genes of miR-155 were forecasted by bioinformatics analysis and confirmed by Western blot. Results TNF-α induced human umbilical vein endothelial cell apoptosis in a dose-dependent and time-dependent manner. Compared with the vehicle control, miR-155 expression increased obviously in human umbilical vein endothelial cells treated with 10 μg/L TNF-α at 24 h (P＜0.01). Over-expression of miR-155 significantly promoted the proliferation of TNF-α-induced human umbilical vein endothelial cells and decreased remarkably their apoptosis (P＜0.01). Interestingly, this effect was obviously reversed in the introduction of the anti-miR-155. Bioinformatics analysis revealed that FADD and Caspase-3 were the potential apoptosis-related target genes of miR-155. Western blot demonstrated that miR-155 negatively regulated Caspase pathways by inhibiting the expression of target genes FADD and Caspase-3. MTT assay and Annexin V-FITC/PI double staining indicated that silencing of Caspase pathways enhanced the pro-proliferation and anti-apoptotic effect of miR-155. Conclusion MiR-155 inhibits TNF-α-induced human umbilical vein endothelial cell apoptosis through down-regulating FADD and Caspase-3 expression.

Abstract:Aim By examining the level of CD45 protein expression in coronary atherosclerotic lesions, and to analyze the relationship between CD45 and lesions structure changes and explore the role of CD45 in the development of coronary atherosclerotic lesions in humans. Methods Specimens of coronary arteries were obtained from Forensic Judicial Expertise Center, Guizhou Medcial University with coronary atherosclerosis. The coronary arteries were classified into three groups according to the lesions:control, atherosclerosis, atherosclerosis and secondary lesion. Routine HE staining of paraffin sections was performed to observe the histological structure of coronary artery in the three groups. The expression level of CD45 protein was detected by immunohistochemical staining, Western blot and Real-time PCR. The relationship between the expression of CD45 and the structural changes of atherosclerotic lesions were analyzed. Results (1)Compared with the control group, the thickness of the fibrous cap in the coronary arterial plaque with atherosclerosis and secondary lesions became thinner, and the thickness of the lesion, the thickness of the necrosis lesion, and the lumen area of the vessel increased (P<0.05). (2)There was a statistically significant difference in the expression of CD45 protein between vascular tissues. (3)There was a statistically significant difference in the expression of CD45 between the control group, the atherosclerosis group and the secondary lesions, and it was mainly expressed in the all leukocytes of the plaques shoulder and bottom. (4)There was a statistically significant difference in the expression of CD45 mRNA between three groups. (5) CD45 expression was related to lesion structure changes. Conclusion The level of CD45 expression reflects the extent of inflammation in human coronary atherosclerotic plaque, and the extent of inflammation within the lesion can affect the structure of the lesion.

Abstract:Aim To investigate the expression of autophagy level in the aorta of type 1 diabetic rats and the intervention effect of rapamycin, and determine whether rapamycin has a protective effect on the aorta of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and apoptosis. Methods Male SD rats were randomly divided into three groups:normal control group, diabetes mellitus group, and rapamycin intervention group. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin. The rats in the rapamycin intervention group were given rapamycin in a dose of 2 mg/kg once a day by gavage. After rapamycin treatment for 8 weeks, blood samples were collected for biochemical indicators and adiponectin detection. The protein or mRNA expression of Beclin1, microtubule-associated protein light chain 3 (LC3), p62, C/EBP homologous protein (CHOP), Caspase-12, glucose-regulated protein 78 (GRP78), Bax and Bcl-2 were assayed by Western blot or real-time fluorescence quantitative PCR. Results Compared with normal control group, the level of serum adiponectin in diabetic rats was significantly decreased (P＜0.05), aortic wall was thicker, endothelium was severely damaged, the mRNA and protein expression of Beclin1 and LC3 and the mRNA expression of Bcl-2 in aorta were significantly decreased (P＜0.05), and the mRNA and protein expression of p62, CHOP, Caspase-12 and GRP78 and the mRNA expression of Bax in aorta were significantly increased (P＜0.05).Compared with diabetes mellitus group, the level of serum adiponectin in rapamycin intervention group was significantly increased (P＜0.05), the pathological changes of aorta tissue were significantly alleviated, the mRNA and protein expression of Beclin1 and LC3 and the mRNA expression of Bcl-2 in aorta were significantly increased (P＜0.05), and the mRNA and protein expression of p62, CHOP, Caspase-12 and GRP78 and the mRNA expression of Bax in aorta were significantly decreased (P＜0.05). Conclusions The level of autophagy in aorta tissue of diabetic rats decreased. Rapamycin may protect the aorta of diabetic rats by activating autophagy and alleviating endoplasmic reticulum stress and cell apoptosis.

Abstract:Aim To establish a model of vascular calcification in SD rats and observe the role of testosterone in aortic calcification. Methods 10-week-old SD male rats were divided into control group, calcification group, calcification+low-dose testosterone group, calcification+high-dose testosterone group, with 8 rats in each group. In addition to the control group, the other three groups were induced with vascular calcification in rats by vitamin D3 (300 kU/kg intramuscular injection) and nicotine (25 mg/kg dissolved in peanut oil in the morning and evening); The rats were injected 1 mg/kg exogenous testosterone (once every other day) in low-dose testosterone group, 2 mg/kg testosterone (once every other day) in high testosterone group, and sacrificed after 2 months. The serum testosterone and bone morphogenetic protein 4 (BMP-4) levels were determined by ELISA method. The calcium and alkaline phosphatase (ALP) contents in vascular tissues were detected by kit. The protein expression levels of BMP-4 and osteopontin (OPN) in aortic vascular tissues were detected by Western blot. Von Kossa staining was used to observe vascular calcification. Results (1) The model of vascular calcification in rats was successfully prepared:Von Kossa staining showed a large amount of black granule-like calcium deposits in the vascular media of rats in the calcified group, while the vascular structure of the control group was intact and no black calcium deposits were observed. (2) Effects of testosterone on vascular calcification:calcium content, ALP, BMP-4, OPN levels were significantly lower in the testosterone group than those in the calcification group (P<0.01), lower in the high-dose testosterone group than in the low-dose testosterone group, and the lowest in the control group; Von Kossa staining showed a large amount of black granular calcium deposits in the vascular media of the calcification group, while a small amount of calcium salt deposits in the low-dose testosterone group and the high-dose testosterone group, and no calcium salt deposits in the control group. Conclusion Exogenous testosterone can alleviate vascular calcification induced by vitamin D3 and nicotine in rats to some extent.

Abstract:Aim To investigate the effect of aortic valve calcification (AVC) on the clinical characteristics and prognosis of patients with acute coronary syndrome (ACS) undergone percutaneous coronary intervention (PCI). Methods A total of 68 ACS inpatients with echocardiographic AVC and 106 ACS controls without AVC undergone PCI were consecutively enrolled from January 2014 to January 2016 in the division of cardiology in our hospital. The clinical and angiographic data of the patients were collected and followed up for two years by two cardiology physicians. Results The prevalences of dyslipidemia (77.9% vs 38.7%), type 2 diabetes mellitus (47.1% vs 24.5%) and arrhythmia (37.3% vs 15.2%) were significantly higher in the AVC group than the control goup (all P＜0.05). In addition, the Gensini score was significantly higher in the AVC group than the control goup (P＜0.05). The multivariate Cox regression model showed that aortic valve calcification, arrhythmia and type 2 diabetes mellitus were all independent worse prognostic risk factors of ACS(all P＜0.05). Conclusions ACS patients with AVC undergone PCI presented with higher co-morbidities of dyslipidemia, type 2 diabetes mellitus and arrhythmia in this pilot study. AVC was associated with the severity of coronary stenosis and more stents implantation in ACS patients. Assessment of AVC by means of transthoracic echocardiography could be a valuable non-invasive method for risk stratification of ACS patients.

Abstract:Aim To explore the correlation between D-dimer (D-D), procalcitonin (PCT), vitamin D (VitD) and coronary artery disease (CAD). Methods 180 patients with CAD were divided into stable angina pectoris group, unstable angina pectoris group and acute myocardial infarction group according to ACC/AHA diagnostic guidelines. The patients were also divided into single vessel lesion group, double vessel lesion group and three vessel lesion group according to the results of coronary angiography (CAG). 62 patients with normal CAG were used as control group. The differences of general clinical data and serum D-D, PCT, VitD levels were compared between CAD group and control group, and the differences of these three indexes were compared among each group. Results The levels of serum D-D and PCT in CAD group were higher than those in control group, while the serum VitD level was lower than that in control group (P＜0.05). In stable angina pectoris group, unstable angina pectoris group and acute myocardial infarction group, D-D and PCT levels increased in turn, while VitD level decreased in turn (P＜0.05). With the increase of the number of coronary artery lesions, the levels of D-D and PCT increased, and the level of VitD decreased. With the increase of Gensini score, D-D and PCT levels increased, while VitD level decreased. Conclusion The levels of serum D-D and PCT in patients with CAD increase with the severity of lesions, while serum VitD level is opposite.

Abstract:Aim To compare the middle and long term prognosis and analyze the influencing factors of chronic total occlusion (CTO) in different branches of coronary artery after percutaneous coronary intervention (PCI) revascularization. Methods A total of 122 patients with CTO confirmed by selective coronary angiography were divided into different branches of lesions according to the lesion location of CTO(left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA)). 113 of them were tried to implement PCI, and the prognosis (survival rate, major adverse cardiac events, left ventricular function) of those with successful PCI and non-revascularization (including unsuccessful PCI and non-PCI) were observed through following up. The middle and long term effects of different branches of CTO after revascularization were compared, and the clinical factors that affect the prognosis were analyzed. Results Among the 113 CTO patients who underwent PCI, 81 cases were successfully revascularized (including 30 cases of RCA, 32 cases of LAD, 5 cases of LCX and 14 cases of two or more branches lesions). The cumulative event-free survival rate in the successful PCI revascularization group was significantly higher than that in the non-revascularization group (70.4% vs 58.5%, P=0.042) during the mean follow-up of (26.7±20.7) months, and the total incidence of adverse events was significantly lower than that in the non-revascularization group (24.7% vs 56.1%, P=0.021). In RCA group, LAD group and two or more CTO lesions group, the incidence of recurrent angina pectoris, heart failure, MACE and all-cause death in those successfully treated with revascularization were significantly lower than that of non-revascularization group (P value of these groups was 0.2,0.7,0.013, respectively). There was no significant difference in LCX group (P=0.408). The total increased left ventricular EF ((3.1±1.4)%) after successful PCI in all patients with CTO was significantly higher than that in the non-revascularization group ((0.3±1.2)%, P=0.038). The ΔEF ((3.6±1.7)%, (4.1±1.8)%,Pü value =0.5,0.038), ΔLAD (P value =0.1,0.035), ΔLVEDD (P value=0.2,0.024), ΔLVESD (P value=0.8,0.031) and ΔRAD (P value=0.7,0.028) after successful revascularization in the RCA group and LAD group was significantly different compared with the same group of patients without revascularization. There was no significant difference about ΔEF(P value=0.5,0.475), ΔLAD (P value = 0.5,0.236), ΔLVEDD (P value=0.7,0.381), ΔLVESD (P value =0.8,0.341), ΔRAD (P value =0.6,0.256) in LCX group and two or more branches group after successful PCI revascularization. Cox proportional risk regression analysis showed that the prognostic factors of CTO patients after PCI revascularization included diabetes history (95%CI:1.253～8.449, P=0.015), serum total bilirubin (95%CI:0.874～0.996, P=0.038), serum uric acid levels(95%CI:1.001～1.007, P=0.006) and J-CTO scores (95%CI:1.135~5.325, P=0.012). Conclusions Successful PCI revascularization of coronary CTO lesions can improve the overall cumulative event-free survival rate in the middle and long term. However, there are differences in the incidence of recurrent angina pectoris, heart failure, MACE, all-cause death and the improvement of left ventricular EF in different branches of CTO lesions. Diabetes history and higher J-CTO scores increases the risk of middle and long term death in CTO patients.

Abstract:Aim To evaluate the efficacy and safety of paclitaxel-coated balloon (PCB) in the treatment of primary macroangiopathy of coronary artery (vessel diameter≥2.8 mm). Methods A prospective, randomized and controlled study was conducted in 100 consecutive patients with coronary heart disease who underwent coronary intervention in our hospital from January 2013 to December 2016. The patients were randomly divided into PCB group and drug-eluting stent (DES) group, with 50 cases in each group. The basic clinical data, the results of immediate coronary intervention and re-examination of angiography, and the long-term incidence of major adverse cardiovascular events were compared between the two groups. Results (1)There were no significant differences in age, blood pressure, blood lipid, smoking, past hypertension, diabetes mellitus and PCI history between the two groups (P＞0.05). (2)The ratio of single coronary artery lesion in PCB group was lower than that in DES group (60.0% vs 70.0%, P＝0.02). There was no significant difference in the ratio of double vessel lesions, three vessel lesions and left main vessel lesions between the two groups (P＞0.05). (3)There was no significant difference in preoperative minimal lumen diameter (MLD) between PCB group and DES group (P＜0.05). The MLD of PCB group was smaller than that of DES group immediately after operation, and the MLD of follow-up was larger than that of DES group (P＜0.05). There was no significant difference in late lumen loss between the two groups. (4)There was no significant difference in the incidence of major adverse cardiovascular events between PCB group and DES group. There were no deaths or recurrent acute myocardial infarction events in both groups during the follow-up period. Conclusion PCB is safe and effective in the treatment of primary macroangiopathy of coronary artery, and the long-term positive vascular remodeling is better than DES to some extent.

Abstract:Aim To explore the value of early blood pressure variability (BPV) in predicting the risk of symptomatic intracerebral hemorrhage (sICH) after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Methods AIS patients were collected who received recombinant tissue plasminogen activator IVT within 4.5 hours of onset from 2012 to 2016 with complete clinical data. According to skull CT or MRI findings and NIHSS scores within 48 hours after IVT therapy, the patients were divided into sICH group (22 cases) and non-sICH group (157 cases). The differences of sICH risk factors between the two groups were analyzed by single factor t test, χ² test and multivariate Logistic regression analysis. The 24-hour systolic blood pressure standard deviation (24hSBPsd) and 24-hour diastolic blood pressure standard deviation (24hDBPsd) were further divided into four groups in quartiles, with the lowest quartile group as the reference group, and the rest groups were compared with the reference group, respectively. Results Univariate analysis showed that age, fibrinogen (FIB), smoking history, 24hSBPsd and 24hDBPsd in sICH group were higher than those in non-sICH group (all P＜0.05). Multivariate Logistic regression analysis showed that age (OR 3.7,5% CI 1.089-8.920), smoking history (OR 2.3,5% CI 1.042-8.257) and 24hSBPsd (OR 4.5,5% CI 1.397-12.237) in sICH group were still higher than those in non-sICH group (all P＜0.05); There was no significant difference in FIB and 24hDBPsd between the two groups (P＞0.05). After adjusting for risk factors of age and smoking history, the risks of sICH in 24hSBPsd and 24hDBPsd of the highest quartile group were 10.882 times (95%CI 2.088-56.717) and 6.025 times (95%CI 1.550-23.417) higher than those of the lowest quartile group, respectively, and the differences were statistically sigificant (P＜0.05). Conclusion The higher the early BPV, the higher the risk of sICH after IVT, and the more obvious the influence of systolic blood pressure variability.

Abstract:The vascular endothelial cell (VEC) is a single layer of flat squamous epithelium covering the intima of the blood vessel. It constitutes a biological barrier to the blood vessel wall. It is not only a protective barrier but also produces some autocrine secretion. The substance is used to regulate homeostasis and vascular tone and has a variety of biological functions. VECsenescence can lead to vascular dysfunction, which is a major risk factor for cardiovascular system (CVS) and has a close relationship with cardiovascular disease (CVD). However, themechanism of VEC senescence and the effects of VEC senescence on vascular function are not fully understood. This review summarizes the characteristics of VEC senescence and its related molecular mechanisms, and describes age-related CVD.

Abstract:Eukaryotic translation initiation factor 2α (eIF2α) is a regulatory subunit of eukaryotic translation initiation factor 2 and is the key protein to catalyze the initiation of protein synthesis. Previous studies have confirmed that phosphorylated eIF2α can play a negative feedback regulation on protein synthesis. Recent studies have found that phosphorylated eIF2α can also specifically activate the translation of certain mRNA to synthesize specific proteins to regulate the expression of target genes, thereby promoting the occurrence and development of diseases. It has been found that eIF2α is differentially expressed in proliferative diseases such as atherosclerosis, pulmonary arterial hypertension and tumors. These evidences suggest that eIF2α may play an important role in human proliferative diseases such as cardiovascular diseases and tumors. Therefore, further exploring the role and mechanism of eIF2α in proliferative diseases is of great significance for the prevention and treatment of proliferative diseases such as cardiovascular diseases and tumors.

Abstract:Trimethylamine oxide (TMAO) is a product which is formed by the metabolism of choline and other substances depending on the intestinal microflora. In recent years, studies at home and abroad have found that TMAO plays an important role in the occurrence and development of atherosclerosis (As). TMAO promotes As by mediating inflammatory signals and gene expression in vascular endothelial cells, increasing thrombosis risk, increasing scavenger receptor and promoting foam cell formation, influencing cholesterol transport pathways and metabolic pathways. This paper summarizes the related literatures in recent years, and finds that by controlling diet, regulating intestinal flora, inhibiting trimethylamine precursor metabolism, inhibiting flavin monooxygenase activity, TMAO level in blood circulation can be reduced and As progress can be prevented.

Abstract:Vascular calcification (VC) is associated with an increased cardiovascular morbimortality in chronic kidney disease (CKD). The prevalence of VC increases steadily through the stages of chronic kidney disease. Well-designed clinical trials are urgently needed to test the potential value of these biomarkers as a guide for interventions targeting VC now. This review gives a brief overview of the circulating biomarkers of vascular calcification in CKD patients.