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Danlou Tablet Improves Chronic Intermittent Hypoxia-Induced Dyslipidemia and arteriosclerosis by HIF-1α-Angptl4 mRNA Signaling Pathway

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Chinese Journal of Integrative Medicine 2022年第6期28卷 509-517页

作者： TANG Jing-jing LI Guang-xi LIU Zhi-guo YI Rong YU Dong ZHANG Yue-bo ZHAO Shuang-qiao WANG Shi-han Department of Pneumology Guang’anmen HospitalChinese Academy of Chinese Medical SciencesBeijing100053China Department of Pulmonary and Critical Care Medicine Mayo ClinicRochesterMN55905USA Drug Clinical Trial Agency Guang’anmen HospitalChinese Academy of Chinese Medical SciencesBeijing100053China Department of Cardiovascular Medicine Mayo ClinicRochesterMN55905USA Department of Gynecology Guang’anmen HospitalChinese Academy of Chinese Medical SciencesBeijing100053China Department of Cardiovascular Medicine Guang’anmen HospitalChinese Academy of Chinese Medical SciencesBeijing100053China

Objective:To detect whether Danlou Tablet(DLT)regulates the hypoxia-induced factor(HIF)-1α-angiopoietin-like 4(Angptl4)mRNA signaling pathway and explore the role of DLT in treating chronic intermittent hypoxia(CIH)-induced dyslipidemia and arteriosclerosis.Methods:The mature adipocytes were obtained from3 T3-L1 cell culturation and allocated into 8 groups including control groups(Groups 1 and 5,0.1 mL of cell culture grade water);DLT groups(Groups 2 and 6,0.1 mL of 1,000μg/mL DLT submicron powder solution);dimethyloxalylglycine(DMOG)groups(Groups 3 and 7,DMOG and 0.1 mL of cell culture grade water);DMOG plus DLT groups(Groups 4 and 8,DMOG and 0.1 mL of 1,000μg/mL DLT submicron powder solution).Groups1-4 used mature adipocytes and groups 5-8 used HIF-1α-siRNA lentivirus-transfected mature adipocytes.After 24-h treatment,real-time polymerase chain reaction and Western blot were employed to determine the mRNA and protein expression levels of HIF-1αand Angptl4.In animal experiments,the CIH model in ApoE^(-/-)mice was established.Sixteen mice were complete randomly divided into 4 groups including sham group,CIH model group[intermittent hypoxia and normal saline(2 mL/time)gavage once a day],Angptl4 Ab group[intermittent hypoxia and Angptl4 antibody(30 mg/kg)intraperitoneally injected every week],DLT group[intermittent hypoxia and DLT(250 mg/kg)once a day],4 mice in each group.After 4-week treatment,enzyme linked immunosorbent assay was used to detect the levels of serum total cholesterol(TC)and triglyceride(TG).Hematoxylin-eosin and CD68 staining were used to observe the morphological properties of arterial plaques.Results:Angptl4 expression was dependent on HIF-1α,with a reduction in mRNA expression and no response in protein level to DMOG or DLT treatment in relation to siHIF-1α-transfected cells.DLT inhibited HIF-1αand Angptl4 mRNA expression(P<0.05 or P<0.01)and reduced HIF-1αand Angptl4 protein expressions with DMOG in mature adipocytes(all P<0.01),as the effect on HIF-1αprotein also existed in the presence of si

关键词： Danlou Tablet Chinese medicine hypoxia-induced factor angiopoietin-like 4 dyslipidemia arteriosclerosis

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Potential Effects of Desalinated Seawater on arteriosclerosis in Rats

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Biomedical and Environmental Sciences 2017年第10期30卷 762-766页

作者： DUAN Lian ZHANG Li Xia ZHANG Shao Ping KONG Jian ZHI Hong ZHANG Ming LU Kai ZHANG Hong Wei Department of Toxicology Institute for Environmental Health and Related Product SafetyChinese Center for Disease Control and PreventionBeijing 100021China Chinese Center for Disease Control and Prevention Beijing 102206China

To evaluate the potential risk of arteriosclerosis caused by desalinated seawater, Wistar rats were provided desalinated seawater over a 1-year period, and blood samples were collected at 0, 90, 180, and 360 days. Blood calcium, magnesium, and arteriosclerosis-related indicators were investigated. Female rats treated with desalinated seawater for 180 days showed lower magnesium levels than the control rats （P 〈 0.05）. The calcium and magnesium levels in female rats and the magnesium level in male rats were lower than the levels in the controls, following treatment with desalinated seawater for 360 days （P 〈 0.05）. Blood levels of arteriosclerosis-related lipid peroxidation indicators and C-reactive protein （CRP） in the treatment group did not differ from those in the controls. The levels of lipid peroxidation indicators and CRP in rats were not significantly affected by drinking desalinated seawater, and no increase in risk of arteriosclerosis was observed.

关键词： Desalinated seawater Lipid peroxidation CRP arteriosclerosis

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arteriosclerosis Obliterans Presenting as Multiple Leg Ulcers: A Case Report

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International Journal of Dermatology and Venereology 2019年第3期2卷 189-190页

作者： Lei Shao Rui-Hua Fang Jjiang Wu Qun Li Li-Jie Chen Jian-Qin Wang Institute of Dermatology Guangzhou Medical UniversityGuangzhouGuangdong510095China Department of Dermatology Guangzhou Institute of DermatologyGuangzhouGuangdong510095China Department of Dermatology Guangzhou FirstPeople's HospitalGuangzhou Medical UniversityGuangzhouGuangdong510180China.

Introduction arteriosclerosis obliterans (ASO) is characterized by the ischemic symptoms of lower extremity,which are due to the stenosis and/or occlusion of artery based on the pathology of atherosclerotic change,mainly involving the large-and medium-sized arteries.Pain and ulcers of the leg are the main causes of patient seeking medical aid;however,a presentation of multiple ulcers is rare.Herein we report a case of ASO presenting as multiple leg ulcers.

关键词： Introduction arteriosclerosis obliterans (ASO) the ischemic symptoms pathology

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Effect of arteriosclerotic intracranial arterial vessel wall enhancement on downstream collateral flow

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Chinese Medical Journal 2023年第18期136卷 2221-2228页

作者： Liqun Yan Jin Yan Zhenchang Wang Guoshi Wang Zhenzhong Li Yaping Hou Boyuan Huang Qianbo Dong Xiaodan Mu Wei Cao Pengfei Zhao Department of Radiology Beijing Friendship Hospital of Capital Medical UniversityBeijing 100050China Departments of Medical Imaging Second Hospital of Hebei Medical UniversityShijiazhuangHebei 050004China Department of Clinical Medicine Tianjin Medical UniversityTianjin 300203China Departments of Neurology Second Hospital of Hebei Medical UniversityShijiazhuangHebei 050004China Hebei Province Blood Center ShijiazhuangHebei 050000China

Background:The effect of arteriosclerotic intracranial arterial vessel wall enhancement(IAVWE)on downstream collateral flow found in vessel wall imaging(VWI)is not clear.Regardless of the mechanism underlying IAVWE on VWI,damage to the patient’s nervous system caused by IAVWE is likely achieved by affecting downstream cerebral blood flow.The present study aimed to investigate the effect of arteriosclerotic IAVWE on downstream collateral flow.Methods:The present study recruited 63 consecutive patients at the Second Hospital of Hebei Medical University from January 2021 to November 2021 with underlying atherosclerotic diseases and unilateral middle cerebral artery(MCA)M1-segment stenosis who underwent an magnetic resonance scan within 3 days of symptom onset.The patients were divided into 4 groups according to IAVWE and the stenosis ratio(Group 1,n=17;Group 2,n=19;Group 3,n=13;Group 4,n=14),and downstream collateral flow was analyzed using three-dimensional pseudocontinuous arterial spin labeling(3D-pCASL)and RAPID software.The National Institutes of Health Stroke Scale(NIHSS)scores of the patients were also recorded.Two-factor multivariate analysis of variance using Pillai’s trace was used as the main statistical method.Results:No statistically significant difference was found in baseline demographic characteristics among the groups.IAVWE,but not the stenosis ratio,had a statistically significant significance on the late-arriving retrograde flow proportion(LARFP),hypoperfusion intensity ratio(HIR),and NIHSS scores(F=20.941,P<0.001,Pillai’s trace statistic=0.567).The between-subject effects test showed that IAVWE had a significant effect on the three dependent variables:LARFP(R^(2)=0.088,F=10.899,P=0.002),HIR(R^(2)=0.234,F=29.354,P<0.001),and NIHSS(R^(2)=114.339,F=33.338,P<0.001).Conclusions:Arteriosclerotic IAVWE significantly reduced downstream collateral flow and affected relevant neurological deficits.It was an independent factor affecting downstream collateral flow and NIHSS scores,which should be a focus of f

关键词： Intracranial arterial vessel wall enhancement arteriosclerosis Stroke Cerebral collateral flow Three-dimensional pseudo-continuous arterial spin-labeling Magnetic Resonance Imaging

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Clinical and prognostic features in asymptomatic and symptomatic patients with arteriosclerosis obliterans

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World Journal of Cardiovascular Diseases 2012年第1期2卷 1-7页

作者： Hiromichi Ohsaka Kazunori Shimada Kosuke Fukao Eiryu Sai Yoshifumi Fukushima Hiroshi Masuda Kuniaki Hirose Takuma Yoshihara Rie Matsumori Makoto Hiki Takashi Kiyanagi Atsumi Kume Haruyo Yamashita Tetsuro Miyazaki Hiroyuki Daida 不详

Background: Patients with arteriosclerosis obliterans (ASO) often have co-existing atherosclerotic diseases. The purpose of this study was to examine the clinical features of patients with ASO, including the overlap of atherosclerotic risk factors, characteristics of car-diovascular events, and clinical prognosis. Method: We enrolled 205 consecutive patients who had ankle brachial index (ABI) of ?0.9 between January 2008 and December 2009. Fontaine (F) classification and clinical background were evaluated and clinical events including mortality and major adverse cardiocerebro-vascular events (MACCEs) were determined. Results: There was a high prevalence of each risk factor. Sixty- five percent of subjects had three or more of the four overlapping risk factors, including hypertension, dia- betes, dyslipidemia, and smoking. After a maximum follow-up of 800 days, the incidence of MACCEs and mortality was 46% and 10%, respectively. We divided the patients into two groups according to the presence of ASO symptoms (F1 and F2-4) and compared the incidence of events. The incidence of MACCEs and mortality in the F2-4 group was significantly higher than that in the F1 group (P = 0.048, P = 0.044, respectively). After excluding lower extremity revascularization, coronary artery disease was a common cause of MACCEs, and the mortality rates after MACCEs increased in a stepwise manner according to F classification severity (P = 0.028). Conclusion: Patients with ASO had overlapping coronary risk factors and a high incidence rate of cardiovascular events. The incidence of coronary events was common, especially in symptomatic patients, and the mortality rates after MACCEs were high in accordance with F classification severity.

关键词： arteriosclerosis Obliterans Fontaine Classification Risk Factor Mortality Cardiocerebrovascular Event

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Sphingosine signaling and atherogenesis

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Acta Pharmacologica Sinica 2004年第7期25卷 3-8页

作者： Jacob HANSEN-SCHWARTZ,Lars EDVINSSON Department of Clinical Experimental Research Glostrup University Hospital Glostrup Denmark Division of Experimental Vascular Research Institute of Medicine Lund University Sweden

Sphingosine-1-phosphate (S1P) has diverse biological functions acting inside cells as a second messenger toregulate cell proliferation and survival, and extracellularly, as a ligand for a group of G protein-coupled receptors(GPCRs) named the endothelial differentiation gene (EDG) family. Five closely related GPCRs of EDG family(EDG1, EDG3, EDG5, EDG6, and EDG8) have recently been identified as high-affinity S1P receptors. Thesereceptors are coupled via Gi, Gq, G12/13, and Rho. The signaling pathways are linked to vascular cell migration,proliferation, apoptosis, intracellular Ca2+ mobilization, and expression of adhesion molecules. The formation of anatherosclerotic lesion occurs through activation of cellular events that include monocyte adhesion to the endothe-lium and vascular smooth muscle cell (VSMC) migration and proliferation. Thus, S1P signaling may play animportant role in the pathogenesis of atherosclerotic vascular disease. This review highlights S1P signalling invascular cells and its involvement in the formation of atherosclerotic lesions.

关键词： sphingosine 1-phosphate sphingosine kinase sphingosine-1-phosphate receptors endothelium myocardium smooth muscle arteriosclerosis

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Comparison of coronary plaque composition among patients with acute coronary syndrome and stable coronary artery disease

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Chinese Medical Journal 2008年第6期121卷 534-539页

作者： LI Xin-ming HUANG Cong-xin WANG Tian-song ZHUANG Shao-wei ZHOU Hua TIAN Bei Department of Cardiology Renmin Hospital of Wuhan UniversityWuhan Hubei 320089 China Department of Cardiology Shanghai East Hospital Affiliated toTongji University Shanghai 200120 China

Background The identification of vulnerable plaques before rupture is an important clinical goal. The purpose of the present study was to assess the difference in plaque composition among patients with acute coronary syndrome （ACS） and stable coronary artery disease （SCAD） by intravascular ultrasound virtual histologic analysis. Methods One hundred and thirty-nine patients were divided into ACS group and SCAD group according to clinical presentation. A total of 229 de novo lesions with 〉50% stenosis in native coronary arteries with diameters 〉2.5 mm were studied with intravascular ultrasonography. Geometric and compositional data were obtained using intravascular ultrasound virtual histology software. Results There were no significant differences in overall lesions for fibrous （（52.0±11.9）% vs （54.3±8.5）%, P〉0.05）, fibrolipidic （（12.3±10.1）% vs （13.8±9.5）%,P〈0.05）, calcium （（14.0±9.1）% vs （19.3±13.1）%, P〉0.05）, or necrotic core （（22.0±11.1）% vs （19.7±5.4）%, P〉0.05） percentages in ACS and SCAD patients, respectively. There were also no significant differences in culprit lesions for fibrous （（46.4±12.0）% vs （53.6±8.8）%, P〉0.05）, fibrolipidic （（9.1±9.0）% vs （12.9±9.7）%, P〉0.05）, calcium （（16.6±9.7）% vs （21.8±26.3）%, P〉0.05）, or necrotic core （（28.0±12.6）% vs （20.6±5.2）%, P〉0.05） percentages in ACS and SCAD patients, respectively. High density lipoprotein-cholesterol levels 〉1.04 mmol/L were associated with more fibrolipidic （（14.5±10.4）% vs （7.1±6.5）%, P〈0.05） and less necrotic core （（20.6±9.7）% vs （27.9±12.6）%,P〈0.05） percentages in the cohort with ACS. Conclusions In this study, coronary plaque composition assessed by intravascular ultrasound virtual histologic analysis was not significantly different between ACS and SCAD patients. The anatomic relationship of the specific plaque components to the lumen of the vessel was more important than the quantitative information of plaque composition for plaque stability.

关键词： coronary plaque composition acute coronary syndrome coronary artery disease ultrasonography, interventional arteriosclerosis

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Effect of probucol on vascular remodeling due to atherosclerosis in rabbits： an intravascular ultrasound study

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Chinese Medical Journal 2011年第12期124卷 1840-1847页

作者： LI Ting-ting XIE Yi GUO Yuan TIAN Hong-bo ZHANG Jian-ning PENG Jie ZHANG Yun Department of Cardiology Qilu Hospital Shandong University Jinan Shandong 250012 China Department of Intensive Care Unit Qilu Hospital Shandong University Jinan Shandong 250012 China Department of Respiratory Medicine Shandong Chest HospitalJinan Shandong 250013 China Department of Cardiology Shandong Provincial HospitalAffiliated to Shandong University Jinan Shandong 250021 China

Background Probucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the effect of probucol on vascular remodeling in a rabbit model of established atherosclerosis. Methods Aortic atherosclerosis was induced by a combination of endothelial injury and 10 weeks＇ atherogenic diet. Animals were then randomized to receive the foregoing diet without or with 1% （wt/wt） probucol for 16 weeks. At the end of week 26, in vivo intravascular ultrasound, pathological, immunohistochemical and gene expression studies were performed. Results Probucol significantly decreased vessel cross-sectional area, plaque area and plaque burden without effect on lumen area. More negative remodeling and less positive remodeling occurred in the abdominal aortas of probucol group than the control group （56% vs. 21%, 18% vs. 54%, respectively, both P〈0.01）. In addition, the probucol group showed a smaller mean remodeling index relative to the control group （0.93 ± 0.13 vs. 1.05 ± 0.16, P 〈0.01）. Furthermore, probucol treatment decreased macrophage infiltration, inhibited apoptosis of cells within plaques, and reduced the production of matrix metalloproteinases-2, -9, cathepsin K and cathepsin S （all P 〈0.01）. Conclusions These findings suggest that probucol may attenuate the enlargement of atherosclerotic vessel walls and be associated with a negative remodeling pattern without affecting the lumen size. This effect may involve inhibition of extracellular matrix degradation and prevention of apoptosis in atherosclerotic plaques.

关键词： arteriosclerosis intravascular ultrasonography, plaque, vascular remodeling probucol

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Effect of homocysteine on plaque formation and oxidative stress in patients with acute coronary syndromes

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Chinese Medical Journal 2004年第11期117卷 1650-1654页

作者：王广毛节明王宪张福春 Institute of Vascular Medicine Peking University Third Hospital Beijing 100083 China Department of Physiology Basic Medical College Peking University Beijing 100083 China Department of Cardiology Peking University Third Hospital Beijing 100083 China

Background Cardiovascular diseases, especially coronary artery disease (CAD), are major causes of death in industrialized countries. Elevated concentrations of plasma homocysteine (Hcy) have been associated with an increased risk of CAD. Increased plasma levels of chemokine, characterized by their ability to induce migration and activation of leukocytes, may contribute to the pathogenesis of CAD. This study was designed to investigate the changes of plasma Hcy, monocyte chemoattractant protein-1 (MCP-1) and oxidative stress markers in acute coronary syndrome patients.Methods A total of 149 subjects were divided into four groups: 50 patients with unstable angina, 30 patients with acute myocardial infarction, 20 coronary restenosis patients after percutaneous coronary intervention and 49 healthy control subjects. Plasma levels of Hcy, MCP-1, malondialdehyde and superoxide dismutase were measured.Results Plasma levels of Hcy and MCP-1 showed significant increases in unstable angina, acute myocardial infarction and restenosis patients compared with control subjects (P<0.05, respectively). Plasma levels of malondialdehyde were significantly increased in unstable angina and acute myocardial infarction patients when compared with control subjects (P<0.05, respectively). Plasma superoxide dismutase levels were significantly reduced in acute myocardial infarction patients when compared with control group (P<0.01).Conclusion Hcy might act as an atherogenic factor through promoting chemokine, reactive oxigen species and oxidized low density lipoprotein production and thereby convert a stable plaque into an unstable potentially occlusive lesion.

关键词： homocysteine arteriosclerosis cytokines

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Aortic arch and intra-/extracranial cerebral arterial atherosclerosis in patients suffering acute ischemic strokes

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Chinese Medical Journal 2003年第12期116卷 1840-1844页

作者：郭毅姜昕陈实张少文赵宏文吴瑛 Departments of Neurology Second Affiliated Hospital of Jinan University Departments of Neurology Cardiology Second Affiliated Hospital of Jinan University Departments of Neurology and Ultrasonic Diagnosis Second Affiliated Hospital of Jinan University

OBJECTIVE: To determine the distribution of aortic arch and intra/extracranial cerebral arterial atherosclerosis in Chinese patients who had suffered acute ischemic strokes. METHODS: Eighty-nine patients with acute ischemic strokes were included in this study. Transesophageal echocardiography (TEE) was used to evaluate potential sources of embolisms in the aortic arch and in the heart; duplex ultrasound was used for the carotid artery; and intracranial Doppler (TCD) imaging was used for the middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), and basilar artery (BA). An atherosclerotic lesion in the aortic arch was defined as normal (0); mild plaque (1); moderate plaque (2); and protruding plaque or mobile plaque (3). A lesion in the carotid artery was considered a plaque if the maximal carotid plaque thickness was 1.2 mm. TCD results were deemed abnormal if flow velocity was either greater or lower than normal, and, in the case of the MCA, if an asymmetry index above 21% was measured. RESULTS: Of the 89 patients, 52 (58.43%) patients showed evidence of aortic arch atherosclerosis (AAA), including 11 (12.36%) patients graded mild, 18 (20.22%) patients graded moderate, and 23 (25.84%) patients graded severe. Of the 23 patients with severe AAA, AAA was determined to be an important potential embolic source in 14 patients. Forty-nine (50.56%) patients had carotid arterial plaques (CAPs). The incidence of carotid plaques was higher among patients with AAA than among patients without AAA (71.15% vs 21.62%, OR = 3.291, 95% CI = 1.740 - 6.225, P

关键词： Acute Disease Aged Aorta, Thoracic Aortic Diseases arteriosclerosis Brain Ischemia Cerebrovascular Accident Female Humans Intracranial arteriosclerosis Intracranial Embolism Male Middle Aged Research Support, Non-U.S. Gov't

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