Abstract:Hydrogen sulfide (H₂S) is now recognized as the third “gasotransmitters” along with nitric oxide (NO) and carbon monoxide (CO) and has been proved to have many biological effects, such as vasodilation, neuroprotection, circadian rhythm regulation and anti-aging. Recent studies have revealed an independent mitochondrial H₂S synthesis pathway, which is different from the cytoplasmic H₂S synthesis mediated by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CGL or CSE). It has been reported that two mitochondrial targeted H₂S donors AP39 and AP123 show stronger cell protection and less cytotoxicity than classical inorganic salt donor NaHS, indicating the particularity of mitochondrial H₂S. This review mainly introduced mitochondrial H₂S about its generation, metabolism and effects on mitochondria. Recent progress of the new mitochondrial targeting H₂S donors are also discussed in this paper, in order to provide a more comprehensive understanding of hydrogen sulfide.

Abstract:Aim To explore the effect of the compatibility of Alisma and Atractylodes on relieving atherosclerosis(As) in ApoE－/－mice and the correlation with reverse cholesterol transport. Methods ApoE－/－ mice were fed with a high-fat diet to construct an animal model of As and treated with Alisma and Atractylodes. The wall thickness, lumen diameter of common carotid artery were measured by ultrasound. HE staining was used to observe the morphology of the artery, and lipid deposition in the liver was observed by oil red O staining. Inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), matrix metalloproteinase-2(MMP-2)were test by ELISA,and matrix metalloproteinase-9(MMP-9) and blood lipid components serum total cholesterol(TC), triglyceride(TG), low density lipoprotein(LDL) and high density lipoprotein(HDL)were analyzed by automatic biochemical analyser. Western blot was used to quantify the expression of silent information regulator protein 1(SIRT1), liver X receptor α(LXRα), ATP-binding cassette transporter A1(ABCA1)and scavenger receptor class B type Ⅰ (SR-BⅠ)in the ApoE－/－ mice liver. Results The compatibility of Alisma and Atractylodes not only significantly repressed the wall thickness, lumen diameter of the common carotid in ApoE－/－ mice, but also reduced the deposition of lipids in the ApoE－/－ mice liver. Treatment with Alisma decoction caused a drop in serum MMP-2, MMP-9, TNF-α, IL-1β, TC, TG, LDL and increase in serum HDL. The expression of SIRT1, LXRα, ABCA1 and SR-BⅠ were markedly up-regulated in the ApoE－/－mice liver treated with Alisma and Atractylodes. Conclusion It was suggested that the compatibility of Alisma and Atractylodes promoted reverse cholesterol transport to reduce liver lipid deposition, suppressed inflammation and improved the morphology of artery via SIRT1-LXRα-ABCA1/SR-BⅠ pathway. It exerted the protective effect in the occurrence and development of As.

Abstract:Aim To explore the effect of lncRNA PVT1 on oxidative stress and cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) and its regulatory effect on miR-761. Methods Rat cardiomyocyte H9c2 cells were treated with hypoxia and reoxygenation (H/R) to establish a cell injury model. si-NC, si-PVT1, miR-mimics-NC, miR-761 mimics, si-PVT1 and miR-inhibitor-NC, si-PVT1 and miR-761 inhibitor were transfected into H/R-induced cardiomyocytes. qRT-PCR method was used to detect the expression of PVT1 and miR-761. Flow cytometry was used to detect the apoptosis rate. The levels of malondialedhyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were detected by Kits. The dual luciferase reporter experiment was used to analyze the targeting relationship between PVT1 and miR-761. Western blot was used to detect the expression of Bcl-2 and Bax protein. Results Compared with the control group, the expression level of PVT1 in the H/R group was increased (P＜0.05), and the expression level of miR-761 was decreased (P＜0.05). Compared with the H/R＋si-NC group, the apoptosis rate and the protein level of Bax were decreased in the H/R＋si-PVT1 group (P＜0.05), the protein level of Bcl-2 and the activities of SOD and CAT were increased (P＜0.05), and the content of MDA was decreased (P＜0.05). Compared with H/R＋miR-mimics-NC group, the apoptosis rate and the protein level of Bax were decreased in H/R＋miR-761 mimics group (P＜0.05), the protein level of Bcl-2 and the activities of SOD and CAT were increased (P＜0.05), the content of MDA was decreased (P＜0.05). The result of dual luciferase report experiment confirmed that miR-761 was the downstream target of PVT1. Interference with miR-761 could obviously reverse the effect of silencing PVT1 on H/R-induced oxidative stress and apoptosis of cardiomyocytes. Conclusion Silencing PVT1 could inhibit H9c2 cell apoptosis and oxidative stress by up-regulating miR-761, thereby reducing H/R-induced cardiomyocyte damage.

Abstract:Aim To investigate the effect and mechanism of fucosyltransferase 8 (Fut8) on the migration of foam cells. Methods The change of Fut8 expression was detected after the foam cell model was established, and the direct relationship between foam cell motility and Fut8 expression was identified. The effects of Fut8 overexpression on the fibrous actin (F-actin) polymerization and the phosphorylation of upstream molecule focal adhesion kinase (FAK) were examined. Results During the formation of foam cells, the expression of Fut8 was significantly down-regulated, and overexpression of Fut8 could repair the impaired migration of foam cells. Expression of F-actin was significantly down-regulated as foam cell motility decreased, and was regulated by Fut8. Phosphorylation of FAK was significantly inhibited when Fut8 expression was down-regulated, and overexpression of Fut8 could result in significantly enhanced phosphory-lation of FAK. Conclusion Inhibition of Fut8-FAK-F-actin pathway may be one of the reasons for the weakening of foam cell motility.

Abstract:Aim To study the effect of cystamine on the proliferation of human pulmonary arterial smooth muscle cells (PASMC) induced by 5-hydroxytryptamine (5-HT) and RhoA signaling pathway. Methods Human PASMC were cultured and stimulated with 1 μmol/L 5-HT and intervened with cystamine. CCK8 assay was used to observe cell proliferation of PASMC. The protein molecules of RhoA signaling pathway were detected by Western blot and co-immunoprecipitation. Results 5-HT induced the proliferation of PASMC, and increased significantly RhoA serotonylation, RhoA membrane translocation, Rho-associated protein kinase 2 (ROCK2) expression, and the phosphorylations of myosin phosphatase target subunit 1 (MYPT1), protein kinase B (Akt) and extracellular regulated protein kinase (ERK). Cystamine inhibited PASMC proliferation, RhoA serotonylation and the phosphorylations of MYPT1, Akt, ERK induced by 5-HT, but had no significant effect on RhoA membrane translocation and ROCK2 protein expression. Conclusion Cystamine inhibits 5-HT-induced proliferation of human PASMC by inhibiting RhoA serotonylation.

Abstract:Aim To investigate the expression of microRNA-129 (miR-129) in serum of patients with chronic systolic heart failure (CSHF) and analyze its relationship with cardiac function indicators. Methods 103 patients with CSHF who were treated in Wuhan Sixth Hospital from May 2016 to October 2018 were selected as the observation group. According to the New York Heart Disease Assocation (NYHA) standard, the observation group was divided into three groups:NYHA class Ⅱ group (33 cases), NYHA class Ⅲ group (28 cases), NYHA class Ⅳ group (42 cases). In addition, 110 healthy people from Wuhan Sixth Hospital at the same time were selected as the control group. The left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) were measured by Philips iEElite type echocardiography, real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of miR-129 in serum, and the correlation between miR-129 and LVESD, LVEDD, LVEF and NYHA classification was analyzed. Results Compared with the control group, the LVESD and LVEDD increased significantly in NYHA class Ⅱ group, NYHA class Ⅲ group and NYHA class Ⅳ group (P＜0.05), while the LVEF and level of miR-129 decreased in turn (P＜0.05). There was no significant difference in serum miR-129 expression among CSHF patients with coronary heart disease, hypertension heart disease and senile heart valve disease(P＞0.05). The serum miR-129 expression of CSHF patients was negatively correlated with LVESD, LVEDD and NYHA grade (P＜0.05), and positively correlated with LVEF (P＜0.05). Conclusion miR-129 is low expressed in the serum of patients with CSHF. It is negatively related to the LVESD, LVEDD and NYHA grade, and positively related to LVEF, which may provide reference for the evaluation of CSHF.

Abstract:Aim To analyze the changes of serum microRNA-224 (miR-224) level after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and its relationship with in-stent restenosis. Methods A total of 212 patients with ACS who were treated from January 2016 to December 2018 were selected as study subjects. They were divided into two groups based on the occurrence of in-stent restenosis:stenosis group (n=42) and non-stenosis group (n=170). The serum miR-224 level of ACS patients was detected by real-time quantitative PCR, and the relationship between miR-224 level and in-stent restenosis was analyzed. Results In 212 patients with ACS who underwent PCI treatment, 42 patients (19.81%) developed in-stent restenosis within 1 year. The low density lipoprotein cholesterol (LDLC), the proportion of diabetes and the length of the stent were higher in the stenosis group than those in the non-stenosis group, and the differences were statistically significant (P＜0.05). The level of serum miR-224 in the two groups showed an increasing trend with time. The 7-day miR-224 level was lower in the stenosis group than that in the non-stenosis group, and the difference was statistically significant (P＜0.05). The 7-day miR-224 assessment of in-stent restenosis in patients with ACS was 0.860, which was higher than the 1-day miR-224 and the 3-day miR-224 (P＜0.05).Logistic multivariate regression analysis showed that LDLC, diabetes, stent length, and 7-day miR-224 level were closely related to in-stent restenosis in ACS patients (P＜0.05). Conclusion The level of miR-224 is closely related to in-stent restenosis at 1 year after PCI in patients with ACS. A low serum miR-224 level at 7 days after PCI in patients with ACS indicates a higher risk of in-stent restenosis.

Abstract:Aim To compare the morphological characteristics of culprit lesions in patients with acute ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTEACS).Methods Clinical data of 93 patients accepting coronary angiography and diagnosed with acute coronary syndrome admitted to Henan Provincial People's Hospital from January 2018 to December 2019 were retrospectively analyzed. According to the type of diagnosis, the patients were divided into STEMI group (45 cases) and NSTEACS group (48 cases).During the operation, optical coherence tomography was used to observe the rupture plaque, plaque lipid composition, fiber cap thickness, thrombus type and lumen area of culprit lesions before interventional therapy. Results The proportions of ruptured plaque (68.9% vs 39.6%, P＝0.005), lipid-rich plaque (88.9% vs 68.8%, P＝0.018), thin-cap fibroatheroma plaque (71.1% vs 37.5%, P＝0.001) and red thrombus (73.3% vs 29.2%, P＝0.006) in STEMI group were significantly higher than those in NSTEACS group. The maximum cross sectional area of plaque break in STEMI group was significantly higher than that in NSTEACS group [(2.45±0.65) mm² vs (1.62±1.01) mm²,P＝0.002]. Conclusion OCT show that the morphology of culprit lesions in STEMI and NSTEACS are different, suggesting that the morphology of ruptured plaque and the type of thrombus in coronary artery are related to the clinical manifestations of acute coronary syndrome.

Abstract:Aim To investigate the effect of different serum potassium concentration on in-hospital death in patients with heart failure. Methods Data of patients hospitalized for heart failure was collected in Department of Cardiology, Shengjing Hospital of China Medical University from January 2013 to December 2018 and a retrospective cohort study database was established. SPSS22.0 software was used for statistical analysis, independent sample t test, χ² test and Logistic analysis were used to clasify the effects of different serum potassium levels on in-hospital death of patients with heart failure. Results The in-hospital death of 9 459 patients with acute decompensation of chronic heart failure was 3.1%. The in-hospital death was the lowest (2.3%) when serum potassium was between 4.0～4.49 mmol/L, 4.2% for serum potassium ＜3.5 mmol/L, 7.7% for serum potassium 5.0～5.49 mmol/L, and 15.1% for serum potassium ≥5.5 mmol/L. Univariate Logistic analysis showed that serum potassium＜3.5 mmol/L and ≥5.0 mmol/L were associated with increased in-hospital death, and the same conclusion was reached after adjusting estimate glomerular filtration rate (eGFR) to exclude the effect of renal function. And the lower(＜3.5 mmol/L) or higher(≥5.0 mmol/L) the serum potassium level was, the greater the risk of in-hospital death. Conclusion Serum potassium level was significantly correlated with in-hospital death in patients with heart failure. The lower or higher the serum potassium level was, the greater the risk of in-hospital death. Maintaining serum potassium level between 3.5～4.49 mmol/L might be better for patients with heart failure.

Abstract:Aim To build a model based on general clinical variables and machine learning method to predict the risk of in-hospital major adverse events (MAE) in patients with Stanford a type aortic dissection (TAAD) after surgery. Methods A total of 1 641 patients with TAAD who underwent surgical treatment in Beijing Anzhen Hospital from January 2013 to December 2017 were included in this study. The individual characteristic variables, clinical signs and the first clinical serum markers on admission were collected. The outcome was defined as in-hospital MAE, including in-hospital death, new acute heart failure after mezzanine, respiratory failure, nervous system disorders, acute renal failure, infection, and unplanned secondary chest opening. The model was constructed after using machine learning to screen variables. Receiver operating characteristic curve (ROC) was used to analyze the ability of the model to predict in-hospital MAE. Net reclassification index (NRI) and integrated discrimination index (IDI) were used to compare the new model with the commonly used clinical models to evaluate the improvement effect of the new model in predicting the prognosis of postoperative TAAD. Finally, the nomogram was established to predict the risk of MAE in patients after TAAD operation. Results The risk prediction model of in-hospital MAE after TAAD operation was determined by using machine learning screening variables, which consisted of D-dimer, creatine kinase isoenzyme, urea, leukocyte count, age, abnormal electrocardiogram and operation time. The area under curve of ROC of in-hospital MAE predicted by the model was 0.776 (95%CI 0.718-0.734, P＜0.001). Compared with the commonly used clinical models, the NRI of our model was 0.654 (95%CI 0.540-0.750, P＜0.001), and the IDI was 0.136 (95%CI 0.117-0.155, P＜0.001), which improved the predictive ability for in-hospital MAE after TAAD operation. The model was presented in the form of nomogram, and the score of nomogram model could evaluate the risk of in-hospital MAE after TAAD operation. ConclusionsBased on machine learning, a model is constructed by using clinical variables of patients. The model can comprehensively evaluate individual characteristic variables, inflammation level, organ damage status and operation status of patients, which has predictive value for postoperative in-hospital MAE of patients with TAAD.

Abstract:Angiogenesis is a process in which existing blood vessels created new vessels under various vascular growth factors control. Pathological angiogenesis is not only regulated by vascular endothelial growth factor (VEGF) but also related to other factors. For instance, inflammatory factors, adhesion molecules, matrix metalloproteinases. Pathological angiogenesis for tumor cells provides the blood supply and nutrients and can help the tumor cells move to distal tissues and organs. Endoplasmic reticulum stress (ERS) is a reaction that intracellular environment change. A slight endoplasmic reticulum stress response may guide the correct protein folding, recover partitions inside the steady-state environment. However, persistent or severe stress leads to a series of diseases. Endoplasmic reticulum stress induces angiogenesis mainly through the activation of three endoplasmic reticulum effectors:X-box binding protein 1, activating transcription factor 4 and splintered activating transcription factor 6. These three effectors can act on downstream pro-angiogenic factors (such as VEGF, IL-8, IL-6, etc.) to promote angiogenesis. Pathologic angiogenesis-related diseases mainly include tumor, atherosclerosis, rheumatoid arthritis, diabetes, etc. This article summarizes the papers concerned with the pathogenic mechanism of endoplasmic reticulum stress and pathological angiogenesis.

Abstract:No reflow phenomenon that occurs after percutaneous coronary intervention is related to adverse cardiovascular events. The mechanisms by which pericytes and endothelial cells can participate in no reflow phenomenon are vital but complicated. This review will discuss the various aspects of the mechanisms.

Abstract:Familial hypercholesterolemia (FH) is an autosomal dominant inherited metabolic disorder, patient with FH has an elevated serum low density lipoprotein cholesterol(LDLC) and a high incidence of premature atherosclerotic cardiovascular disease (ASCVD). If untreated, patients with homozygous familial hypercholesterolemia (HoFH) develop premature death by the age of 30 years, generally from ASCVD. Cholesterol-lowing therapies for HoFH include therapeutic lifestyle changes, lipid-lowing pharmacologic therapy, lipid apheresis and liver transplantation, etc. However, the curative effect of the traditional lipid-lowering drugs is still very limited in HoFH population. It is difficult to carry out lipid apheresis constantly because of its high cost, invasiveness, long-term maintenance at weekly or biweekly interval and poor adherence. Nearly 90% of FH is caused by mutations in the LDL receptor (LDLR) gene. Since LDLR are located mainly in the hepatocytes, liver transplantation achieves the replacement of dysfunctional hepatic LDLR, and it is considered to be the effective way to correct hepatic cholesterol metabolism. This paper mainly review the efficacy and safety of liver transplantation, current challenges and the prospect of liver transplantation for HoFH.

Abstract:Rupture of carotid atherosclerotic plaque is one of the important causes of stroke. A large number of studies have confirmed that carotid plaque neovascularization is an important factor leading to intraplaque hemorrhage and rupture. Inflammatory factors and all kinds of cells enter the plaque through intraplaque neovascularization, which leads to the destruction of plaque stability. But the important related factors and main mechanisms affecting the formation of intraplaque neovascularization are not completely clear. Therefore, to identify intraplaque neovascularization and explore the related factors and mechanism of intraplaque neovascularization is the key to study plaque instability caused by intraplaque neovascularization. Inhibition of intraplaque neovascularization may be a new strategy for prevention and treatment of carotid plaque rupture and reduction of cerebral embolism. The purpose of this review is to explore the related factors, mechanism and the latest research progress of detection and imaging of carotid intraplaque neovascularization, so as to provide support for the diagnosis and treatment of clinical diseases.

Abstract:According to the theory of inflammation, atherosclerosis (As) is an immune inflammatory reaction involving modified lipid particles, monocytes and macrophages. As a part of innate immunity, complement system is an important player in the occurrence and development of As. There are new progress about the role of some complement components in the occurrence and development of As. Complement protein C1q plays a dual role in As, that is, inducing atherogenic and antiatherogenic effects. Complement component C3 is involved in the formation of As and late thrombosis by binding to its receptor or forming non-proteolytic intermediates. Complement component C3a binds to C3a receptor, and C5a binds to C5a receptor 1 or C5a receptor 2, which promote the activation of nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 inflammasome and the secretion of interleukin-1β through different ways, and then promote the occurrence of As. C5b-9 complement complex can induce As by causing endothelial dysfunction, and response gene to complement-32 is the key effect factor.