Hyperhomocysteinemia (HHcy) is considered to be an independent risk factor for cardiovascular diseases, but the molecular mechanisms underlying its pathogenesis are not fully understood. Endothelial dysfunction is a key initiating factor in the pathogenesis of atherosclerosis, which is commonly observed in almost all HHcy-induced vascular diseases. HHcy promotes oxidative stress, inhibits nitric oxide production, suppresses hydrogen sulfide signaling pathway, promotes endothelial mesenchymal transition, activates coagulation pathways, and promotes protein N-homocysteination and cellular hypomethylation, all of which can cause endothelial dysfunction. This article reviews the specific links between HHcy and endothelial dysfunction, and highlights recent evidence that endothelial mesenchymal transition contributes to HHcy-induced vascular damage, with a hope to provide new ideas for the clinical treatment of HHcy-related vascular diseases.
Humans ; Atherosclerosis ; Cardiovascular Diseases ; Endothelium, Vascular ; Homocysteine/metabolism* ; Hyperhomocysteinemia/complications* ; Oxidative Stress ; Risk Factors

Atherosclerosis is a chronic inflammatory disease of vascular walls with a complex etiology. In recent years, the incidence of atherosclerosis continues to increase with obesity and diabetes as major risk factors. As an important metabolic organ in the body, adipose tissue also has a powerful endocrine function. In the case of obesity and diabetes, various cytokines and exosomes derived from adipose tissue mediate organ-organ/cell-cell crosstalk, and are involved in the occurrence and development of various diseases. As an important intercellular communicator, exosomes regulate the pathological process of various cardiovascular diseases and are closely related to atherosclerosis. In this paper, we reviewed the mechanism of adipose-derived exosomes in atherosclerosis with focus on endothelial dysfunction, inflammatory response, lipid metabolism disorder and insulin resistance, hoping to provide reference for the research, diagnosis and treatment of atherosclerosis.
Humans ; Exosomes/metabolism* ; Atherosclerosis ; Obesity/complications* ; Adipose Tissue/metabolism* ; Insulin Resistance

Atherosclerosis ; Humans ; Polysomnography ; Sleep Apnea, Obstructive/complications*

Atherosclerosis ; Diabetes Mellitus, Type 2/complications* ; Dyslipidemias ; Fibroblast Growth Factors ; Humans

OBJECTIVE: To determine the effects of hawthorn extract on serum lipid levels, pathological changes in aortic atherosclerosis plaque, inflammatory factors, and apoptosis-related protein and mRNA expression in apolipoprotein E gene knockout (ApoE) mice. METHODS: Thirty-six ApoE mice were fed with a high-fat diet starting at the age of 8 weeks. Mice were randomly divided into 3 groups by a random number table including model group, hawthorn extract group, and simvastatin group, 12 mice in each group. Twelve 8-week-old C57BL/6 mice were fed a basic diet and served as control. The mice in the control and model groups were administered 0.2 mL saline daily, the mice in the hawthorn extract and simvastatin groups were administered with 50 mg/kg hawthorn extract or 5 mg/kg simvastatin daily for 16 weeks. After 16 weeks, plasma lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by an enzymatic assay. Aortic atherosclerotic lesions were observed by light microscopy, scanning and transmission electron microscopy, respectively. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β), adiponectin (APN), and hypersensitive C-reactive protein (hs-CRP) were measured by enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expressions of Bax and Bcl-2 in the aorta were assessed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. RESULTS: Compared to the control group, the plasma levels of TC, TG and LDL-C were significantly increased and HDL-C were significantly decreased in the model group (P<0.01). Compared to the model group, treatment with hawthorn extract significantly decreased the plasma levels of TC, TG, and LDL-C and increased the plasma level of HDL-C in ApoE mice (P<0.01). The levels of MCP-1, IL-1ß, and hs-CRP in the model group were significantly increased and APN was significantly decreased compared with the control group (P<0.01). Compared to the model group, treatment with hawthorn extract decreased the levels of MCP-1, IL-1ß, and hs-CRP and increased the APN level (P<0.01). Compared to the control group, the protein and mRNA expression of Bax in the model group were significantly increased and the expression of Bcl-2 was significantly decreased (P<0.01). Hawthorn extract also reduced the protein and mRNA expression of Bax and increased the Bcl-2 expression in the aorta (P<0.01). CONCLUSION Hawthorn extract has anti-atherosclerosis and stabilizing unstable plaque effects. The mechanism may be related to the inflflammation and apoptosis signaling pathways.
Animals ; Aorta ; pathology ; ultrastructure ; Apoptosis ; drug effects ; Atherosclerosis ; blood ; complications ; drug therapy ; Crataegus ; chemistry ; Inflammation ; blood ; complications ; drug therapy ; Inflammation Mediators ; metabolism ; Lipids ; blood ; Male ; Mice, Inbred C57BL ; Plant Extracts ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; bcl-2-Associated X Protein ; metabolism

complications are generally caused by a process called atherosclerosis. Evidences suggest that to initiate atherosclerosis, oxidated low-density lipoprotein (oxLDL) has to promote the expression of adhesion molecule. Several studies have evidenced the relevance of oxidative stress and atherosclerosis. However, the protective effect of alpha-lipoic acid (ALA) at atherosclerosis still needs to be explored. This study is aimed at investigating the concentration of plasma oxLDL and the expression of adhesion molecule of type 2 diabetes mellitus (DM) using rat model. Eighteen male rats were segregated into three groups labeled as control group, DM group and DM+ALA group. Type 2 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg) followed by nicotinamide (110 mg/kg). ALA was administered at a dose of 60 mg/kg body weight/day throughout the feeding period of 3 weeks. Plasma oxLDL concentration was measured by enzyme-linked immunosorbent assays and expression of vascular cell adhesion molecule-1 (VCAM-1) was measured by immunohistochemistry. Expression of abdominal aortic adhesion molecule was assessed by calculation with Adobe Photoshop CS3. Analysis of variance test was used to compare the concentration of plasma oxLDL and expression of adhesion molecule. A P-value of 0.05 was considered statistically significant. Plasma oxLDL was lower in diabetic rat+ALA compared with the diabetic rat. Percentage of area VCAM-1 in DM+ALA group was lower than DM group. There were no significant differences between groups in intensity of VCAM-1. In conclusion, ALA showed protective effects against early atherosclerosis in diabetic rats.]]>
Animals ; Atherosclerosis ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunohistochemistry ; Injections, Intraperitoneal ; Lipoproteins ; Male ; Models, Animal ; Niacinamide ; Oxidative Stress ; Plasma ; Rats ; Streptozocin ; Thioctic Acid ; Vascular Cell Adhesion Molecule-1

BACKGROUND: Sarcopenic obesity (SO) is a serious public health concern, few studies have examined the clinical implications of SO in newly-diagnosed type 2 diabetes mellitus (T2DM) patients. We evaluated the prevalence of the newly diagnosed, drug-naïve T2DM patients with low muscle mass with abdominal obesity and its association with insulin resistance and other diabetic complications. METHODS: We classified 233 drug-naïve T2DM subjects into four groups according to abdominal obesity (waist circumference ≥90 cm in men and ≥85 cm in women) and low muscle mass status (appendicular skeletal muscle <7.0 kg/m² for men and <5.4 kg/m² for women). RESULTS: The proportion of the subjects with low muscle mass and abdominal obesity among the newly diagnosed, drug-naïve T2DM patients was 8.2%. Homeostasis model assessment of insulin resistance (HOMA-IR) increased linearly according to body composition group from normal to abdominal obesity to both low muscle mass and abdominal obesity. The multiple logistic regression analysis indicated that subjects with low muscle mass and abdominal obesity (odds ratio [OR], 9.39; 95% confidence interval [CI], 2.41 to 36.56) showed a higher risk for insulin resistance, defined as HOMA-IR ≥3, than those with abdominal obesity (OR, 5.36; 95% CI, 2.46 to 11.69), even after adjusting for other covariates. However, there were no differences in lipid profiles, microalbuminuria, or various surrogate markers for atherosclerosis among the four groups. CONCLUSION: Subjects with both low muscle mass and abdominal obesity had a higher risk of insulin resistance than those with low muscle mass or abdominal obesity only.
Atherosclerosis ; Biomarkers ; Body Composition ; Diabetes Complications ; Diabetes Mellitus, Type 2 ; Homeostasis ; Humans ; Insulin Resistance ; Logistic Models ; Male ; Muscle, Skeletal ; Obesity ; Obesity, Abdominal ; Prevalence ; Public Health

This study aimed to gain insight into the underlying pathogenesis of erectile dysfunction in young men under the age of 40 years without widely-known risk factors. Compared with normal controls, patients with erectile dysfunction had increased carotid intima-media thickness, fasting levels of blood glucose and insulin, and homeostatic model assessment index, as well as lower flow-mediated vasodilation and testosterone levels (P < 0.05), though all of these values were within their respective normal range. Multivariate logistic regression analysis identified carotid intima-media thickness, flow-mediated vasodilation, insulin level, and homeostatic model assessment index as significant predictors of erectile dysfunction. Young men with flow-mediated vasodilation <10.65% were 11.645 times more likely to have erectile dysfunction, young men with carotid intima-media thickness >0.623 mm had a 4.16-fold, and young men with homeostatic model assessment index >1.614 had a 5.993-fold greater risk of having erectile dysfunction. In conclusions, in young men with normal results from general clinical screening, an increased carotid intima-media thickness and homeostatic model assessment index and reduced flow-mediated vasodilation were associated with a higher incidence of erectile dysfunction. Erectile dysfunction may appear before the detection of traditional cardiovascular risk factors and may be the earliest clinical sign of subclinical cardiovascular disease.
Adult ; Atherosclerosis/complications* ; Blood Glucose/analysis* ; Carotid Artery Diseases/epidemiology* ; Carotid Intima-Media Thickness ; Erectile Dysfunction/epidemiology* ; Humans ; Incidence ; Insulin/blood* ; Male ; ROC Curve ; Risk Factors ; Testosterone/blood* ; Ultrasonography ; Vasodilation ; Young Adult

OBJECTIVE: To investigate the relationship between periodontal disease and subclinical atherosclerosis in middle-aged and older adults in Shijingshan community of Beijing. METHODS: In 2005-2010, a total of 830 middle-aged and older adults were recruited from Shijingshan community of Beijing, who were divided into two groups by severity of periodontitis. A questionnaire, periodontal examination, blood biochemical examination, carotid intima-media thickness (CIMT), including common carotid artery (CCA-IMT), internal carotid artery (ICA-IMT) and carotid bifurcation (CB-IMT), were measured of each subject. The associations of periodontitis with CIMT was evaluated by multivariable Logistic regression analysis and analysis of covariance, adjusted for age, gender, education level, hypertension, hyperlipidemia, obesity, smoking, drinking, and diabetes. And then anther definition of periodontitis (mild periodontitis: percentage of AL≥3 mm <10%; moderate periodontitis: percentage of AL≥3 mm 10%-30%; severe periodontitis: percentage of AL≥3 mm ≥30%) was used to investigate the hypotheses that different classification of periodontitis would affect results. RESULTS: The subjects with moderate-severe periodontitis were characterized by significantly higher levels of CCA-IMT, ICA-IMT, CB-IMT and mean CIMT than the mild group. In the univariate analysis, moderate-severe periodontitis was associated with an increased risk of ICA-IMT>0.9 mm (adjusted OR=1.230, 95% CI: 1.058-1.452, P=0.031). Furthermore, moderate periodontitis was associated with an increased risk of CB-IMT>0.9 mm (adjusted OR: 1.297, 95%CI: 1.117-1.753, P=0.011) and severe periodontitis was associated with an increased risk of CB-IMT>0.9 mm (adjusted OR=1.771, 95%CI: 1.176-3.503, P=0.042) according to another classification of periodontitis. CONCLUSION Our data provided evidence that periodontitis was associated with CIMT among middle-aged and older adults in Shijingshan community of Beijing and different periodontitis classification would affect the results.
Aged ; Atherosclerosis/complications* ; Beijing ; Carotid Arteries ; Carotid Artery, Common ; Carotid Artery, Internal ; Carotid Intima-Media Thickness ; Chronic Periodontitis/pathology* ; Diabetes Mellitus ; Humans ; Middle Aged ; Risk Factors

OBJECTIVETo compare the efficacy between acupuncture at stellate ganglion combined with intravenous administration of alprostadil and simple intravenous administration of alprostadil on lower limb atherosclerosis of early diabetes mellitus.

METHODSSixty patients of lower limb atherosclerosis of early diabetes mellitus were randomly divided into an observation group and a control group, 30 cases in each one. Patients in the two groups were treated with basic treatment to control blood glucose and lipid. In addition, patients in the control group were treated with intravenous administration of alprostadil (10 µg) and sodium chloride solution (100 mL); based on this, patients in the observation group were treated with acupuncture at stellate ganglion. The treatment was given once a day; the consecutive treatment of two weeks constituted one session, and totally 4 sessions were given. The total syndrome score, glycosylated hemoglobin (HbA1c), blood flow of posterior tibial artery and dorsal artery of foot were observed before and after treatment; the clinical efficacy was compared between the two groups.

RESULTSCompared before treatment, the total syndrome score, HbA1c, blood flow of posterior tibial artery and dorsal artery of foot were significantly improved after treatment (all P < 0.05), which were more obvious in the observation group (all P < 0.05). After treatment, the total effective rate was 93.3% (28/30) in the observation group, which was significantly superior to 86.7% (26/30) in the control group (P < 0.05). CONCLUSION Acupuncture at stellate ganglion combined with intravenous administration of alprostadil achieve better effect than simple intravenous administration of alprostadil for lower limb atherosclerosis of early diabetes mellitus, which improve the clinical symptoms, regulate blood sugar and increase the blood flow of lower limb.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Atherosclerosis ; etiology ; physiopathology ; therapy ; Diabetes Mellitus, Type 2 ; complications ; Female ; Humans ; Lower Extremity ; blood supply ; innervation ; physiopathology ; Male ; Middle Aged ; Stellate Ganglion ; physiopathology ; Treatment Outcome