Lixisenatide is effective and safe as add-on treatment to basal insulin in Asian individuals with type 2 diabetes and different body mass indices: a pooled analysis of data from the GetGoal Studies.

INTRODUCTION: This analysis aims to investigate the efficacy and safety of once-daily lixisenatide add-on treatment to basal insulin in Asian individuals with type 2 diabetes, by baseline body mass index (BMI). RESEARCH DESIGN AND METHODS: Data from all Asian participants in the placebo-controlled GetGoal-Duo 1, GetGoal-L, and GetGoal-L-C Studies were pooled and categorized according to the following BMI subgroups:<25 kg/m2, 25-<30 kg/m2 and ≥30 kg/m2. Efficacy and safety of lixisenatide versus placebo were evaluated among BMI subgroups. Multivariable regression analyses were also conducted to explore the potential influence of BMI on efficacy outcomes after adjusting for baseline characteristics. RESULTS: 555 participants were included (mean age 53.9 years, 52.4% men). No significant differences in treatment effect between the BMI subgroups were observed for the changes from baseline to 24 weeks in glycated hemoglobin (HbA1c), fasting plasma glucose, postprandial glucose (PPG), PPG excursion, body weight, BMI, and basal insulin dose with lixisenatide, as well as the change in basal insulin dose at study endpoint and the proportion of participants achieving an HbA1c <7% at 24 weeks (all p values for interaction >0.15). In the multivariable regression analysis, participants in the lowest BMI group had a smaller reduction in body weight over the 24-week treatment period relative to the highest BMI group (p=0.023). CONCLUSIONS: This post hoc analysis indicates that lixisenatide improved glycemic control regardless of baseline BMI and was well tolerated in Asian individuals unable to achieve their HbA1c target on basal insulin±oral antidiabetic drugs.

A Guideline-Based Decision Tree Achieves Better Glucose Control with Less Hypoglycemia at 3 Months in Chinese Diabetic Patients.

INTRODUCTION: China has the world's largest diabetes epidemic and has been facing a serious shortage of primary care providers for chronic diseases including diabetes. To help primary care physicians follow guidelines and mitigate the workload in primary care communities in China, we developed a guideline-based decision tree. This study aimed to validate it at 3 months with real-world data. METHODS: The decision tree was developed based on the 2017 Chinese Type 2 Diabetes (T2DM) guideline and 2018 guideline for primary care. It was validated with the data from two registry studies: the NEW2D and ORBIT studies. Patients' data were divided into two groups: the compliance and non-compliance group, depending on whether the physician's prescription was consistent with the decision tree or not. The primary outcome was the difference of change in HbA1c from baseline to 3 months between the two groups. The secondary outcomes included the difference in the proportion of patients achieving HbA1c < 7% at 3 months between the two groups, the incidence of self-reported hypoglycemia at 3 months, and the proportion of patients (baseline HbA1c ≥ 7%) with a HbA1c reduction ≥ 0.3%. The statistical analysis was performed using linear or logistic regression with inverse probability of treatment weighting with adjustments of confounding factors. RESULTS: There was a 0.9% reduction of HbA1c in the compliance group and a 0.8% reduction in the non-compliance group (P < 0.001); 61.1% of the participants in the compliance group and 44.3% of the participants in the non-compliance group achieved a HbA1c level < 7% at 3 months (P < 0.001). The hypoglycemic events occurred in 7.1% of patients in the compliance group vs. 9.4% in the non-compliance group (P < 0.001). CONCLUSION: The decision tree can help physicians to treat their patients so that they achieve their glycemic targets with fewer hypoglycemic risks. ( http://www.clinicaltrials.gov NCT01525693 & NCT01859598).

Comparison of insulin glargine 300 U/mL versus glargine 100 U/mL on glycemic control and hypoglycemic events in East Asian patients with type 2 diabetes: A Patient-level meta-analysis of phase 3 studies.

AIMS: To evaluate efficacy and safety of Gla-300 with Gla-100 in a patient-level meta-analysis among large East Asian patients with type 2 diabetes mellitus (T2DM). METHODS: A patient level meta-analysis of three EDITION studies with similar design and endpoints were conducted over 6-months treatment period. The analysis included 547 patients treated with Gla-300 and 348 patients treated with Gla-100. RESULTS: Over 6-month treatment period, mean change in HbA1c was similar for Gla-300 [Least square (LS) mean, (SE): -1.13 (0.05) % and Gla-100: -1.14 (0.05) %], showing non-inferiority of Gla-300 to Gla-100 (LS mean difference: 0.02%, 95% CI: -0.08 to 0.11). Gla-300 was associated with reduced risk of hypoglycemic event (confirmed ≤ 3.9 mmol/L or severe) vs Gla-100 at any time of day or at night (00:00-05:59 h). The event rates of hypoglycemia were consistently lower with Gla-300 than Gla-100. Severe hypoglycemia was rare in both treatment groups. Weight gain was minimal in both treatment groups. CONCLUSION: Gla-300 provides comparable glycemic control to Gla-100 in East Asian patients with broad clinical spectrum of T2DM, with consistently less hypoglycemia at any time of the day and night.

Efficacy of once-daily glucagon-like peptide-1 receptor agonist lixisenatide as an add-on treatment to basal insulin in Asian and white adults with type 2 diabetes mellitus: An individual-level pooled analysis of phase III studies.

AIMS/INTRODUCTION: The prevalence and pathophysiological background of type 2 diabetes mellitus vary across ethnicities, and can affect treatment responses. Adding lixisenatide to basal insulin (BI) in type 2 diabetes mellitus patients has shown improvements in glycated hemoglobin (HbA1c) and postprandial glycemic (PPG) excursions, without increasing hypoglycemic events. We aim to compare the efficacy of lixisenatide in Asian and white patients inadequately controlled with basal insulin. MATERIALS AND METHODS: An individual-level pooled analysis of two multi-national phase III studies, GetGoal-L and GetGoal-L-C, was carried out to assess the efficacy of lixisenatide versus placebo as an add-on treatment to BI ± metformin in Asian and white patients with type 2 diabetes mellitus. Change in HbA1c, 2-h PPG and PPG excursion were analyzed, along with possible predictors of glycemic control. RESULTS: Pooled data showed that baseline characteristics were similar between Asian and white patients with the exception of bodyweight, body mass index and BI dose being higher in white patients. After 24 weeks, lixisenatide reduced HbA1c in both ethnic groups, with no statistically significant difference between the two groups (Asian patients least squares mean difference -0.49, 95% confidence interval -0.68 to - 0.30 and white patients least squares mean difference -0.45, 95% confidence interval -0.63 to - 0.26; P = 0.6287). Similarly, no significant difference was found in 2-h PPG reduction between both groups (least squares mean difference for Asian vs white patients: -3.37 vs -3.93; P = 0.3203). Treatment with lixisenatide contributed to HbA1c reduction of -0.56% after adjustment of baseline HbA1c level in Asian patients, and -0.41% in white patients. CONCLUSIONS: Adding lixisenatide to BI significantly reduced HbA1c and 2-h PPG levels in both Asian and white participants with type 2 diabetes mellitus. No differences in treatment effect were observed between the two populations.

Bioequivalence Study Comparing Fixed-Dose Combination of Clopidogrel and Aspirin with Coadministration of Individual Formulations in Chinese Subjects Under Fed Conditions: A Phase I, Open-Label, Randomized, Crossover Study.

INTRODUCTION: Simultaneous administration of acetylsalicylic acid (ASA) and clopidogrel has demonstrated efficacy in the treatment of acute coronary syndrome. Clopidogrel + ASA in a fixed-dose combination (FDC) provides a pharmaceutical option to enhance adherence to the coadministration of dual antiplatelet therapy (DAPT). Herein, we evaluate the bioequivalence of enteric ASA and clopidogrel in an FDC compared with simultaneous administration of the individual formulations. METHODS: This study is a randomized, single-center, open-label, three-sequence, three-period, two-treatment, crossover study conducted in healthy Chinese male and female subjects under fed conditions. Subjects were randomized to receive, in each period, a single dose of (1) a combination tablet containing 75-mg clopidogrel and 100-mg enteric ASA (test formulation) or (2) coadministration of one 75-mg clopidogrel tablet and one 100-mg enteric-coated ASA tablet (reference formulations) under fed conditions. Plasma samples were analyzed for ASA, salicylic acid, clopidogrel, and the clopidogrel metabolite SR26334. For ASA, the reference-scaled average bioequivalence (RSABE) analysis was conducted for Cmax of ASA because within-subject standard deviation (SDW) was ≥ 0.294 for log-transformed Cmax. RESULTS: The point estimate (test/reference geometric mean ratio) was between 0.80 and 1.25, and the upper one-sided 95% confidence interval (CI) for the scaled average bioequivalence metric was ≤ 0 (-0.08). AUC of ASA as SDW was < 0.294 for log-transformed AUClast and AUC. Estimates of 90% CIs for log-transformed AUClast and AUC ratios were within the bioequivalence range of 0.80 to 1.25 (0.98-1.08 and 1.00-1.10, respectively). For clopidogrel, the 90% CIs for the ratios comparing log-transformed Cmax, AUClast, and AUC ratios of clopidogrel following administration of test versus reference formulation were calculated using the ABE method and were well within the acceptable range of 0.80 to 1.25 (1.02-1.12, 0.92-0.99, and 0.92-0.98, respectively). CONCLUSION: FDC of ASA and clopidogrel was bioequivalent to the simultaneous administration of the individual formulations in healthy Chinese subjects under fed conditions. TRIAL REGISTRATION: CTR20190376.

Implementation of a Reference-Scaled Average Bioequivalence Approach for Highly Variable Acetylsalicylic Acid in Fixed-Dose Combination with Clopidogrel Versus Enteric Aspirin in Chinese Subjects Under Fasting Conditions: A Phase 1, Open-Label, Randomized, Crossover Study.

INTRODUCTION: Dual antiplatelet therapy, aspirin and a P2Y12 inhibitor, is recommended to prevent thrombotic complications of acute coronary syndrome. Clopidogrel plus acetylsalicylic acid combination is the most commonly used dual antiplatelet therapy recommended by international guidelines and in Chinese clinical practice. Poor adherence to dual antiplatelet therapy or premature interruption of dual antiplatelet therapy is an important contributor to cardiovascular mortality and lethal cardiovascular events. Clopidogrel + acetylsalicylic acid fixed-dose combination enhances adherence to dual antiplatelet therapy. Herein, we aimed to evaluate bioequivalence of acetylsalicylic acid and clopidogrel in fixed-dose combination compared with simultaneous administration of their individual formulations in healthy Chinese subjects under fasting conditions. METHODS: This was a randomized, single-center, open-label, three-sequence, three-period, two-treatment, crossover study with a washout period of 10 days conducted in healthy Chinese volunteers. Subjects were randomized to receive Co-Plavix® (test formulation- fixed-dose combination of 100 mg acetylsalicylic acid and 75 mg clopidogrel) once and reference formulations (coadministration of individual formulations of 100 mg acetylsalicylic acid and 75 mg clopidogrel) twice during the study period. Pharmacokinetic parameters were analyzed for acetylsalicylic acid, its metabolite salicylic acid, clopidogrel, and its metabolite SR26334. As acetylsalicylic acid shows high intrasubject variability, the reference-scaled average bioequivalence (RSABE) approach was implemented for acetylsalicylic acid analysis, while bioequivalence of clopidogrel was assessed using the average bioequivalence method. Point ratios and confidence intervals (CIs) for AUC, AUClast, and Cmax for acetylsalicylic acid and clopidogrel were calculated. RESULTS: In total, 171 healthy subjects were enrolled in this study. Subjects were randomized and 170 subjects were treated with test or reference formulation; 164 subjects completed the study. Regarding acetylsalicylic acid exposure, as reference within-subject standard deviation (SDW) was at least 0.294 for acetylsalicylic acid Cmax, AUClast, and AUC, the RSABE analysis method was used to assess bioequivalence for all three parameters. The point estimates were within the 0.80-1.25 range (1.19, 1.09, and 1.04, respectively), and upper one-sided 95% CIs of scaled average bioequivalence metric were at most 0 (- 0.30, - 0.14, and - 0.10, respectively). Thus, bioequivalence was demonstrated with acetylsalicylic acid. Bioequivalence was also achieved with clopidogrel as the 90% CIs for geometric mean ratios of clopidogrel Cmax, AUClast, and AUC were within the bioequivalence range (0.80-1.25). CONCLUSION: Application of the reference-scaled average bioequivalence approach to evaluate bioequivalence of acetylsalicylic acid in Chinese male and female healthy volunteers under fasting conditions demonstrated bioequivalence of test and reference formulations. TRIAL REGISTRATION: CTR20181695.

Ginsenoside-Rg1 enhances angiogenesis and ameliorates ventricular remodeling in a rat model of myocardial infarction.

Ginsenoside-Rg1 (Rg1) has been used in the traditional Chinese medicine for over 2,000 years. The present study was performed to test our hypothesis that Rg1 provides pro-angiogenic and anti-fibrotic benefits in the ischemic myocardium in a rat model of myocardial infarction. The expression of vascular endothelial growth factor (VEGF) and phosphorylation/activation of PI3K, Akt, and p38 MAPK signaling pathways were examined in human umbilical vein endothelial cells and in the myocardial samples of rats. In addition, the expression levels of TNF-α and collagen I level, the number of newly formed blood vessels, the extent of myocardial fibrosis, and left ventricular function were measured in vivo. Our results demonstrated that administration of Rg1 increased VEGF expression levels, activated PI3K/Akt, and inhibited p38 MAPK in vitro and in vivo. Furthermore, Rg1 increased the density of newly formed vessels, decreased TNF-α and collagen I expression levels and area of myocardial fibrosis, and improved left ventricle function in vivo. PI3K inhibitor LY294002 significantly attenuated Rg1-enhanced VEGF expression and capillary density. As well, inhibition of p38 MAPK slightly increased VEGF expression in vitro and in vivo, increased capillary density, and decreased TNF-α and collagen I expression levels and area of myocardial fibrosis in vivo. Rg1-induced activation of PI3K/Akt also contributed to the downregulation of p38 MAPK. Thus, Rg1 is effective in promoting angiogenesis and attenuating myocardial fibrosis, resulting in ameliorated left ventricular function. The possible mechanisms may involve activation of PI3K/Akt, inhibition of p38 MAPK, and cross talk between the two signaling pathways.

Qindan-capsule inhibits proliferation of adventitial fibroblasts and collagen synthesis.

AIMS: Qindan-capsule (QC) is a prescription of traditional Chinese medicine for the treatment of hypertension. We investigated the effect and mechanism of QC-containing serum on proliferation of aortal adventitial fibroblasts (AFs) and composition of extracellular matrix (ECM). We also tested whether the Smad3 signaling pathway is activated in the progress. MATERIALS AND METHODS: AFs were cultured by tissue explant in vitro. The proliferation of AFs induced by transforming growth factor beta1 (TGF-beta1) and affected by QC-containing serum with high or low dose was detected by MTT. The protein and mRNA expressions of Smad3 and Procollagen I were observed by Western blot and Real-time PCR respectively. RESULTS: Western blot and Real-time PCR revealed that after being activated by TGF-beta1 for 24h, the expressions of Smad3, Pho-Smad3 and Procollagen I were all higher than those in the control group. But these functions were inhibited, to some extent in different doses, by QC-containing serum. So that the proliferation of AFs which was evaluated by MTT. CONCLUSIONS: The results suggested QC-containing serum has significantly improved proliferation of AFs and composition of extracellular matrix. TGF-beta1/Smad3 signaling pathway may be involved in the mechanism.

Effect of traditional Chinese medicine Shu-mai-tang on angiogenesis, arteriogenesis and cardiac function in rats with myocardial ischemia.

Ischemic heart disease is one of the leading causes of morbidity and mortality worldwide. Shu-mai-tang (SMT) is a traditional Chinese medicine for the treatment of ischemic heart disease. To better understand the underlying cardioprotection mechanisms of SMT on myocardial ischemia (MI), the effect of SMT on angiogenesis, arteriogenesis and cardiac function was investigated in a rat model of MI, as well as the potential mechanism. Rats with a ligated left anterior descending coronary artery (MI model) were randomized (24 rats/group) to receive SMT/LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor], SMT or no treatment. A sham-operation group was included. It was demonstrated that 2 and 4 weeks after treatment the oral administration of SMT significantly increased capillaries and arterioles, suppressed myocardial fibrosis, as well as significantly increased cardiac phosphorylation of Akt, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-BB) levels and functional improvement. PI3K inhibitor down-regulated SMT-induced angiogenesis and arteriogenesis. These novel therapeutic properties of SMT to induce the reconstitution of stable blood supply networks, reverse LV remodeling may offer an alternative therapy for the treatment of ischemic heart disease. The potential mechanism may be that SMT promotes VEGF and PDGF-BB-mediated angiogenesis and arteriogenesis through the PI3K/Akt signaling pathway.

Effect of traditional Chinese medicine Shu-Mai-Tang on attenuating TNFalpha-induced myocardial fibrosis in myocardial ischemia rats.

Shu-Mai-Tang (SMT) is a traditional Chinese medicine for treatment of ischemic heart disease. The effect of SMT on inflammation-induced myocardial fibrosis, left ventricular (LV) remodeling, and the potential mechanism in myocardial ischemia (MI) rats were investigated. Rats with ligated left anterior descending coronary artery (MI model) were randomly divided into three groups (SMTL, SMTH, and MIR). A group undergoing Sham operation (Sham; n=16) was also included. SMT (342 or 1710 mg/kg for SMTL or SMTH groups, respectively) was orally administered daily for 1 and 6 weeks. Cardiac function, myocardial fibrosis, serum tumor necrosis factor-alpha (TNFalpha) concentration, the cardiac expressions of phosphorylated p38 MAPK and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TNFalpha were examined by echocardiography, histological staining, radioimmunoassay, western blot, respectively. In the present study, significant reduced myocardial fibrosis, as well as decreased phospho-p38 MAPK, TIMP-1, and TNFalpha proteins, and serum TNFalpha level, accompanied by improved cardiac function in the SMT-treated rats in a dose-dependent manner as compared with the MIR. These results suggested that SMT could anti-inflammation-induced myocardial fibrosis and reverse LV remodeling in MI rats, and the mechanism may be related to the effect of SMT on inhibiting p38 MAPK signaling pathway.

Inhibitory effect of Ginkgo biloba extract on hyperhomocysteinemia-induced intimal thickening in rabbit abdominal aorta after balloon injury.

Ginkgo biloba extract (GBE) has been widely used to treat cardiovascular and cerebrovascular disorders. Hyperhomocysteinemia (Hhcy) is associated with the risk of atherosclerosis and restenosis after angioplasty. The objective of this study was to investigate whether GBE could attenuate the Hhcy-induced intimal thickening after balloon injury in rabbit abdominal aorta. It was observed in this study that GBE could decrease the neointima area (NA) and the ratio of the neointima area to the media area (NA/MA), down-regulate the mRNA expression of matrix metalloproteinase-9 (MMP-9) and up-regulate the protein expression of p21 (WAF1/CIP1) (p21). It suggests that GBE can reverse the Hhcy-induced neointima formation in rabbits following balloon injury, and the suppressive effect of GBE on the migration and proliferation of vascular smooth muscle cells (VSMCs) may contribute to its actions.

Effect of folate on neointima formation and matrix metalloproteinase-9 expression after balloon injury in hyperhomocysteinemic rabbits.

BACKGROUND: It is known that hyperhomocysteinemia (Hhcy) is associated with the risk of restenosis after angioplasty. Folate can lower plasma homocysteine (Hcy) level and alleviate the Hhcy-induced neointima formation after balloon injury. This study aims to explore the mechanisms of folate in inhibiting neointima formation. METHODS: 24 New Zealand White rabbits were randomly divided into three groups: Control, 2% methionine (Meth) and 2% methionine+folate (Meth+folate). At the end of 8 experimental weeks, all rabbits underwent the balloon injury in abdominal aorta. 4 weeks following this procedure, plasma Hcy concentration, aortic maximal neointimal thickness (NT), neointimal area (NA), medial area (MA), and ratio of neointimal area to medial area (NA/MA), ultrastructure of vascular smooth muscle cells (VSMCs), and matrix metalloproteinase-9 (MMP-9) expression were detected by high performance liquid chromatography, histomorphometric analysis, transmission electron microscope (TEM) and real-time PCR, respectively. RESULTS: It was observed in our study that Hcy concentration, NT, NA, NA/MA and the expression of MMP-9 mRNA were higher in the Meth group than in the control. VSMCs in media exhibited typical synthetic phenotype in the Meth group compared with the transitional state between contractile phenotype and synthetic phenotype in the control group. However, in the rabbits treated with folate, Hcy concentration, NT, NA and MMP-9 mRNA expression were lower than those in the Meth group. The phenotype of VSMCs was close to that in the control group. CONCLUSION: This study suggested that folate could decrease the level of Hcy, reverse the Hhcy-induced exacerbation of neointima formation in rabbits following balloon injury, and the mechanisms in it may be related to the suppressive effect of folate on the expression of MMP-9 mRNA in arterial wall.

p38 mitogen-activated protein kinase inhibition decreases TNFalpha secretion and protects against left ventricular remodeling in rats with myocardial ischemia.

The purpose of this study was to test our hypothesis that p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 may favorably affect tumor necrosis factor alpha (TNFalpha) secretion and left ventricular (LV) remodeling after myocardial ischemia (MI). The left anterior descending coronary artery (LAD) was ligated to produce anterior MI in 40 rats that were randomly divided into two groups: p38i group (n = 24) and MIR group (MI rat models, n = 24). A sham operation group without LAD ligation (Sham, n = 16) was also studied. SB203580 (2 mg/kg) and saline was injected i.p. once every 3 days in the first two groups, respectively. One and six weeks after MI, cardiac function, myocardial fibrosis, the cardiac expressions of phosphorylated p38 MAPK (p-p38 MAPK), TNFalpha, alpha smooth muscle actin (alphaSMA) and collagen I, the ultramicrostructure of the myocardium were examined by echocardiography, histological staining, western blot, immunohistochemical staining, transmission electron microscope (TEM), respectively. Treatments with SB203580 suppressed myocardial fibrosis and LV remodeling, as well as attenuated the expressions of p-p38-MAPK, TNFalpha, alphaSMA and collagen I as compared with the MIR. In conclusion, SB203850 has an effect of inhibiting inflammation-induced fibrosis, which leads to attenuation of LV remodeling.

Improvement of vascular remodeling in spontaneous hypertensive rats with traditional Chinese medicine.

Qin-Dan-Jiang-Ya-Tang (QDJYT) is a traditional Chinese herbal medicine for the treatment of hypertension. The effect of QDJYT on blood pressure (BP) and vascular remodeling in hypertension was investigated in the model of spontaneous hypertensive rats (SHR). Sixteen SHRs were divided into two groups: the SHR group and the SHR+ QDJYT group. Eight Wistar-Kyoto (WKY) rats were in the normal control group. QDJYT (750 mg/kg) was orally administered daily for 12 weeks to the SHR+QDJYT group. After 12 weeks, thoracic aortas were segregated. The media thickness (MT) and the lumen diameter (LD) of the aortic wall, the ratios of MT to LD, the expression of basic fibroblast growth factor (bFGF) mRNA, and the level of its proteinic production were examined by histology, real-time PCR, and Western blot analysis, respectively. It was observed in our study that MT, MT/LD, the expression of bFGF mRNA, and the level of its proteinic production in aortic walls were higher in SHRs than in WKY rats. However, in the SHRs treated with QDJYT, we found MT, MT/LD, the expression of bFGF mRNA and the level of its proteinic production were lower than SHRs. These results suggest that QDJYT can improve the vascular remodeling in SHRs, and the mechanisms may be related to the suppressive effect of QDJYT on bFGF mRNA and its proteic productions in the aortic walls of SHRs.

[Experimental study on effect of Shumai capsule in promoting angiogenesis in rats with myocardial ischemia].

OBJECTIVE: To study the effect of Shumai Capsule (SMC) on angiogenesis and expression of relevant growth factor in rats with myocardial ischemia (MI). METHODS: Model rats of MI were duplicated and treated with SMC (SMC group), bFGF + calparine (positive control group) and normal saline (model group) respectively. Besides, a sham-operative group was set up and treated with normal saline. The rats were sacrificed in batches at the time after being medicated for 1, 2 and 4 weeks, for determining von Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) protein expression in ischemic myocardium by immuno-histochemical staining, myocardial micro-vessel density (MVD) using digital analysis system, and the gene expression of VEGF by quantitative real-time PCR. RESULTS: Compared with the sham-operative group and the model group, levels of MVD, protein and gene expression of VEGF in the SMC group were higher respectively at three time segments (all P <0.01), but showed insignificant difference to those in the positive control group. CONCLUSION: SMC could promote angiogenesis in ischemic myocardium of rats, the up-regulation on VEGF mRNA and protein expression might be one of the potential mechanisms of SMC in promoting angiogenesis.

Effect of traditional Chinese medicine Qin-Dan-Jiang-Ya-Tang on remodeled vascular phenotype and osteopontin in spontaneous hypertensive rats.

Qin-Dan-Jiang-Ya-Tang (QDJYT) is a traditional Chinese herbal medicine for the treatment of hypertension. The effect of QDJYT on blood pressure and on vascular remodeling in hypertension was investigated in the model of spontaneous hypertensive rats (SHR). Sixteen SHRs were divided into two groups, the SHR group and the SHR+QDJYT group. Eight WKY rats were a normal control group. QDJYT (750 mg/kg) was orally administered daily for 12 weeks in SHR+QDJYT group. After 12 weeks, thoracic aortas were segregated. Media thickness (MT), lumen diameter (LD), the ratio of MT to LD, the volume fraction of collagen (VFC) in media, the ultrastructure of vascular smooth muscle cells (VSMCs) and the expression of osteopontin (OPN) mRNA were examined by histological staining, transmission electron microscope (TEM), and real-time PCR, respectively. It was observed in our study that MT, MT/LD, VFC and the expression of OPN mRNA were higher in the SHRs than in the WKY rats, volume and numeral density of mitochondria in vascular smooth muscle cells (VSMCs) in media increased obviously. However, in the SHRs treated with QDJYT, we found MT, MT/LD, VFC and the expression of OPN gene were lower than in the SHRs, and the phenotype of VSMCs were close to normal. These results suggest that QDJYT could reverse the vascular remodeling in SHR, and the mechanisms may be related to the suppressive effect of QDJYT on the expression of OPN mRNA in arterial wall.