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

OBJECTIVETo explore the effects of Dangua Recipe (DGR) on glycolipid metabolism, serum reactive oxygen species (ROS) level, nuclear factor kappa B (NF-kappaB) positive expression and its mRNA expression level in the thoracic aorta of diabetic rats with atherosclerosis, thus revealing its partial mechanisms for intervening chronic diabetic complications.

METHODSRecruited 40 Goto-Kakisaki (GK) Wistar rats were fed with high fat forage containing metabolic inhibition Propylthiouracil, and peritoneally injected with endothelial NOS inhibitor N-nitro-L-arginine methyl ester to establish a high fat diabetes model with atherosclerosis. The modeled GK rats were stratified by body weight, and then, by blood glucose level from high to low, randomly divided into the DGR group (at the daily dose of 8 mL/kg), the metformin group (MET, at the daily dose of 150 mg/kg), the simvastatin group (SIM, at the daily dose of 2 mg/kg), and the model group (MOD, fed with pure water, at the daily dose of 8 mL/kg) according to the random number table, 10 in each group. Another 10 Wistar rats of the same ages and comparable body weight level were recruited as the normal control group. All the interventions lasted for 24 weeks by gastrogavage. The fasting blood glucose (FBG) and body weight were monitored. The HbA1c, TC, LDL-C, HDL-C, TG, serum ROS were determined. The aortic NF-kappaB level was analyzed with immunohistochemical assay. The expression of NF-kappaB (P65) mRNA in the aorta was detected with Real-time PCR.

RESULTSThe body weight in the normal control group was eventually heavier than others (P < 0.01). There was no difference among the four groups of GK modeled rats (P > 0.05). The FBG in the four GK modeled groups were higher than that in the normal control group (P < 0.01, P < 0.05). There was no statistical difference in the blood glucose level at the first visit and at the baseline among the GK modeled groups (P > 0.05). The last FBG level was obviously lower in the MET and DGR groups than in the MOD group (P < 0.01) and the SIM group (P < 0.05). Twenty-four weeks after intervention, the level of FBG, HbA1c, TC, LDL-C, HDL-C, and NF-kappaB positive expression rate of the thoracic aorta of the four groups of GK modeled rats, and NF-kappaB mRNA expression in the thoracic aorta in the MOD group, the MET group, and the DGR group were significantly higher than those in the normal control group (P < 0.01, P < 0.05). The TG level, serum ROS in the MET, DGR, and SIM groups, and the NF-kappaB mRNA expression level in the thoracic aorta in the SIM group were significantly lower than those in the normal control group (P < 0.01, P < 0.05). The levels of FBG, TC, LDL-C, serum ROS, NF-kappaB mRNA expression level in the thoracic aorta in three drug intervention groups, and NF-kappaB positive expression rate in the DGR and MET groups, and the levels of HbA1c, TG in the DGR group were significantly lower than those in the MOD group (P < 0.01, P < 0.05). The level of FBG in the MET and DGR groups were lower than that in the SIM group (P < 0.05). The level of NF-kappaB mRNA expression in the thoracic aorta of the SIM and DGR groups, and the levels of TC and LDL-C in the DGR group were significantly lower than those in the MET group (P < 0.01).

CONCLUSIONDGR played a role in preventing and treating chronic diabetic complications by comprehensively regulating blood glucose and serum lipids, as well as down-regulating oxidative stress.

Animals ; Aorta, Thoracic ; metabolism ; Atherosclerosis ; complications ; drug therapy ; metabolism ; Blood Glucose ; analysis ; Diabetic Angiopathies ; drug therapy ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Lipid Metabolism ; Male ; NF-kappa B ; metabolism ; Oxidative Stress ; Phytotherapy ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; blood

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

OBJECTIVETo research the effects and mechanism of Shenqi compound (SQC) on PTEN/ PI3K signal transducing path and angiogenesis in Goto-Kakizaki (GK) rats with diabetes mellitus type 2 (DM2) caused macroangiopathy.

METHODGK rats with blood sugar > or = 11.1 mmol/L were divided into 4 groups, the GK group, the model group, the Western medicine (WM) group treated by atorvastatin 1.5 mg/(kg x d) and the Chinese medicine (CM) group treated with SQC 1.44 g/(kg x d). All were fed 35 days with high fatty diet, but to the latter three groups, N omega-nitriyl-L-arginine methyl ester 0.1 mg/mL was added into their drinking water for macroangiopathy model establishing. Besides, a group of normal Wistar rats fed with ordinary forage was set for control. Rat's blood glucose and lipids were measured, morphology of abdominal aorta wall tissue was observed with HE staining, and mRNA expressions of PTEN and PI3Kp85 in aortic wall were detected by Real-time PCR.

RESULTSGeneral condition, gluco-lipid metabolism and aortic morphology in the CM group were significantly better than those in the model group. PTEN mRNA expression in the CM group (1.10 +/- 0.48) was significantly higher than that in the GK group (0.63 +/- 0.16) and the model group (0.17 +/- 0.07, both P < 0.01), but near to that in the WM group (1.11 +/- 0.46), while the PI3Kp85 mRNA expression in the TCM group (0.19 +/- 0.05) was lower than that in the GK group (1.38 +/- 0.43, P < 0.01), but near to that in the model group (0.33 +/- 0.09) and the WM group (0.11 +/- 0.06, both P > 0.05).

CONCLUSIONSQC could increase the PTEN mRNA expression and restrain the PI3Kp85 mRNA expression in aorta, which is possibly the partial mechanisms of action of the remedy in inhibiting angiogenesis and preventing diabetic macroangiopathy.

Angiogenesis Inhibitors ; pharmacology ; therapeutic use ; Animals ; Aorta ; metabolism ; Astragalus membranaceus ; chemistry ; Atherosclerosis ; prevention & control ; Class Ia Phosphatidylinositol 3-Kinase ; genetics ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Diabetic Angiopathies ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Male ; PTEN Phosphohydrolase ; genetics ; metabolism ; Panax ; chemistry ; Phytotherapy ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred Strains ; Rats, Wistar ; Signal Transduction ; drug effects

BACKGROUNDIncreased risk of atherosclerosis has been reported in patients with human immunodeficiency virus (HIV) infection since highly active antiretroviral therapy (HAART) has come into use. However, there is no clear evidence of premature atherosclerosis in Chinese HIV-infected patients. Our study was designed to determine the relationship between HIV infection and atherosclerosis in Chinese HIV-infected patients.

METHODSOne hundred and forty-five patients were enrolled in this study. These included 82 HIV-infected patients (41 HAART-treated and 41 antiretroviral therapy (ART) naïve patients) and 43 HIV-negative control subjects. Data on traditional cardiovascular risk factors, HIV infection parameters, and treatment regimens were collected. Pulse wave velocity (PWV) was determined using a pulse pressure analyzer to evaluate the function of the arterial wall as an indicator of atherosclerotic vascular damage.

RESULTSA higher PWV ((1358.3 ± 117.8) cm/s vs. (1270.2 ± 189.2) cm/s, P = 0.010) was found in ART naïve HIV-infected patients compared with control subjects. However, HAART treated patients had lower PWV compared to ART naïve patients ((1283.8 ± 181.4) cm/s vs. (1358.0 ± 117.8) cm/s, P = 0.033). Multiple regression analysis revealed that age (B = 5.218, 95% confidence interval (CI) 1.420 - 9.016, P = 0.008), current smoking (B = -74.671, 95%CI -147.003 to -2.339, P = 0.043) and HAART (92.7% patients on a protease inhibitor-free regimen) (B = -169.169, 95%CI -272.508 to -65.831, P = 0.010) were associated with reduced PWV in HIV-infected patients.

CONCLUSIONSReduced PWV in HIV-infected Chinese patients indicates that they are more likely to develop arterial wall stiffness, possibly by atherosclerosis. A protease inhibitor-free regime may be protective for arterial wall of HIV infected patients.

Acquired Immunodeficiency Syndrome ; complications ; drug therapy ; physiopathology ; Adult ; Antiretroviral Therapy, Highly Active ; Atherosclerosis ; etiology ; Female ; Humans ; Male ; Middle Aged ; Pulsatile Flow ; Regression Analysis ; Vascular Stiffness

Aged ; Angiography ; Angioplasty, Balloon ; methods ; Atherosclerosis ; complications ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Renal Artery Obstruction ; diagnostic imaging ; etiology ; therapy ; Treatment Outcome ; Ultrasonography

Angioplasty, Balloon ; methods ; Atherosclerosis ; pathology ; therapy ; Humans ; Hypertension ; complications ; drug therapy ; Renal Artery Obstruction ; etiology ; therapy ; Stents

AIMTo evaluate whether the response to sildenafil administration in patients with arterial erectile dysfunction (ED) was related to their peak systolic velocity (PSV), peripheral atherosclerosis, cardiovascular risk factors (RF) and/or comorbidities at low cardiovascular risk.

METHODSWe enrolled 97 patients with 1-2 RF and comorbidities, combined with arterial ED alone (group A, n = 27), ED plus atherosclerotic carotid artery (group B, n = 23), ED plus lower limb artery abnormalities (group C, n = 25), and ED plus carotid and lower limb artery abnormalities (group D, n = 22). Sildenafil efficacy (100 mg twice a week for 12 weeks) was also examined in patients with =or>3 RF, peripheral atherosclerosis and no cardiovascular comorbidities (group E, n = 20).

RESULTSMedian PSV was 24.1, 21.0, 19.3, 14.5 and 17.5 cm/s in groups A, B, C, D and E, respectively. Sildenafil response was higher in group A patients (77.8%), intermediate in groups B and C (65.2% and 56%) and lowest in groups D (45.4%) and E (50%), and the response in latter two groups was significantly lower than in the other three groups. In addition, sildenafil response was negatively influenced by: =or>3 RF, peripheral atherosclerosis and no systemic comorbidity, or presence of 1-2 RF associated with extended atherosclerosis and comorbidities. The number of comorbidities was positively related to atherosclerosis localization or extension (25, 35, 38 and 47 in groups A, B, C and D, respectively).

CONCLUSIONLow sildenafil efficacy in patients with arterial ED was associated with extended atherosclerosis. These patients should undergo extensive ultrasonography and a full cardiovascular examination.

Aged ; Arterial Occlusive Diseases ; complications ; drug therapy ; physiopathology ; Atherosclerosis ; complications ; Cardiovascular Diseases ; complications ; drug therapy ; Erectile Dysfunction ; drug therapy ; etiology ; physiopathology ; Humans ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Physical Examination ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Regional Blood Flow ; physiology ; Retrospective Studies ; Risk Factors ; Sildenafil Citrate ; Sulfones ; therapeutic use ; Treatment Outcome ; Vasodilator Agents ; therapeutic use

OBJECTIVETo observe the effect of Wendan Xiezhuo method (WXM) on carotid arteriosclerosis and vascular endothelial diastolic function in essential hypertension (EH) patients with turbid-phlegm syndrome (TPS).

METHODSForty-three EH patients of medium and low risk with TPS were randomly assigned to two groups, the Wendan Tablet (WT) group (23 cases) and the placebo group (20 cases), they were treated with WT and placebo respectively on the base of amlodipine treatment to control the blood pressure. Carotid intimamedia thickness (IMT), atherosclerotic plaque score of carotid artery, endothelium-dependent dilation (EDD) and flow-mediated vasodilation (FMD) of brachial artery after taking nitroglycerin were detected with ultrasonography before and after 6 months of treatment.

RESULTSAs compared with those in the placebo group, in the WT group after treatment, scores of TPS and carotid plaque were better, area of carotid plaque was lesser and IMT was lower significantly (P<0.05 or P<0.01). There was a negative correlation between brachial artery EDD and carotid IMT in EH patients with TPS (r = - 0.596, P < 0.05). After treatment EDD was improved more significantly in the WT group than that in the placebo group, however, no significant difference was found in non-endothelium-dependent dilation between the two groups.

CONCLUSIONA negative correlation exists between brachial artery EDD and carotid IMT, and the latter could be aggravated by TPS in EH patients. WXM shows favorable effects in improving carotid plaque and EDD.

Aged ; Atherosclerosis ; complications ; pathology ; physiopathology ; Carotid Arteries ; diagnostic imaging ; drug effects ; physiopathology ; Carotid Artery Diseases ; complications ; diagnostic imaging ; pathology ; Drugs, Chinese Herbal ; therapeutic use ; Endothelium, Vascular ; drug effects ; pathology ; physiopathology ; Female ; Humans ; Hypertension ; complications ; drug therapy ; pathology ; Male ; Middle Aged ; Phytotherapy ; Syndrome ; Treatment Outcome ; Ultrasonography