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ABSTRACT: This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation with this disease in order to identify AF patients who are at high risk of stroke and need optimal anticoagulant therapy. A total of 103 AF patients, simple (n=75) or complicated by ischemic stroke (n=28), and 112 control subjects were recruited. IL-6 level was detected by using enzyme linked immunosorbent assay. Cystatin C and hsCRP levels were measured by means of a particle-enhanced immunonephelometric assay. The results showed that the AF patients had higher levels of hsCRP (P=0.004), IL-6 (P=0.000), and cystatin C (P=0.000) than control subjects. Plasma hsCRP level was increased in the AF patients with ischemic stroke as compared to the patients with simple AF (P=0.036). The AF patients who had the level of hsCRP exceeding 3.83 mg/L were at a higher risk than those with hsCRP level lower than 3.83 mg/L (P=0.030). After adjusting for other factors, cystatin C remained positively associated with IL-6 (r=0.613) and hsCRP (r=0.488). It was concluded that hsCRP is positively correlated with ischemic stroke complicating AF and may be a risk factor independent of other risk factors for AF. Elevated cystatin C level is also indicative of the increased risk of AF.
Journal of Huazhong University of Science and Technology 10/2010; 30(5):648-51. · 0.38 Impact Factor
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Gang Yuan,
Juanjuan Deng,
Tao Wang, Chunxia Zhao,
Xizheng Xu,
Peihua Wang,
James W Voltz,
Matthew L Edin,
Xiao Xiao,
Lee Chao,
Julie Chao,
Xin A Zhang,
Darryl C Zeldin,
Dao Wen Wang
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ABSTRACT: We previously reported that iv delivery of the human tissue kallikrein (HK) gene reduced blood pressure and plasma insulin levels in fructose-induced hypertensive rats with insulin resistance. In the current study, we evaluated the potential of a recombinant adeno-associated viral vector expressing the HK cDNA (rAAV-HK) as a sole, long-term therapy to correct insulin resistance and prevent renal damage in streptozotocin-induced type-2 diabetic rats. Administration of streptozotocin in conjunction with a high-fat diet induced systemic hypertension, diabetes, and renal damage in rats. Delivery of rAAV-HK resulted in a long-term reduction in blood pressure, and fasting plasma insulin was significantly lower in the rAAV-HK group than in the control group. The expression of phosphatidylinositol 3-kinase p110 catalytic subunit and the levels of phosphorylation at residue Thr-308 of Akt, insulin receptor B, and AMP-activated protein kinases were significantly decreased in organs from diabetic animals. These changes were significantly attenuated after rAAV-mediated HK gene therapy. Moreover, rAAV-HK significantly decreased urinary microalbumin excretion, improved creatinine clearance, and increased urinary osmolarity. HK gene therapy also attenuated diabetic renal damage as assessed by histology. Together, these findings demonstrate that rAAV-HK delivery can efficiently attenuate hypertension, insulin resistance, and diabetic nephropathy in streptozotocin-induced diabetic rats.
Endocrinology 06/2007; 148(5):2016-26. · 4.46 Impact Factor
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ABSTRACT: Peroxisome proliferator-activated receptors alpha (PPARalpha) is a target gene for atherosclerosis and cardiovascular diseases. However, effects of PPARalpha on endothelial nitric oxide synthase (eNOS) remain unknown. We investigated the eNOS regulation by bezafibrate, a ligand of PPARalpha, and involved signaling pathways.
Firstly, in cultured bovine aorta endothelial cells (BAEC), bezafibrate significantly upregulated eNOS at protein, mRNA levels and NO production, respectively, in a concentration-dependent fashion (50-200muM). Next, the effects of bezafibrate on signal pathways and eNOS mRNA stability in BAEC were investigated. Results showed that bezafibrate induced phosphorylation of MAPK. Inhibitors of PPARalpha, PI3 kinase and MAPK, respectively, markedly attenuate bezafibrate-induced upregulation of eNOS. Bezafibrate incubation increased eNOS mRNA half-life, activated eNOS promoter, enhanced phosphorylation of eNOS ser-1179 site, and decreased phosphorylation of eNOS thr-497 site via activating ERK and Akt.
Bezafibrate can upregulate eNOS expression, enhance phosphorylation of eNOS ser-1179, increase NO production and transcription level and stability of eNOS mRNA through pathway dependent of PPARalpha and nongenomic effects mediated by MAPK and PI3K pathways. Hence, PPARalpha ligands exert direct benefits on vessel endothelial functions through an increase in eNOS expression level and phosphorylation of eNOS ser-1179. This mechanism provides additional anti-atherosclerotic and anti-hypertension benefits of bezafibrate in addition of lipid-lowering effects.
Atherosclerosis 09/2006; 187(2):265-73. · 3.79 Impact Factor
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ABSTRACT: Adrenomedullin (AM) is a hypotensive peptide that functions as an important regulator in the cardiovascular and renal systems. The current study explored the potential therapeutic effects of delivering the human AM cDNA via a novel double-stranded adeno-associated virus vector (dsAAV) on hypertension and related complications in spontaneously hypertensive rats (SHR). A single dose of dsAAV-AM vector administered by tail vein injection into adult SHR resulted in significant reduction of systolic blood pressure at 2 weeks after gene delivery. This effect was observed through the entire duration of the experiment period (up to 16 weeks). Administration of dsAAV-AM also resulted in a decrease in total urine microalbumin content. Left ventricle and cardiomyocyte hypertrophy, fibrosis in the heart, glomerular sclerosis, and tubular injuries in the kidney were significantly reduced. Moreover, deterioration of hemodynamic variables was prevented in treated rats, as compared with the control groups. We conclude that AAV-mediated AM delivery can render a longterm and stable reduction of hypertension and protect against renal injury and cardiac remodeling in the spontaneously hypertensive rat model. Further preclinical studies are warranted for the development of a gene therapy strategy for human hypertension.
Human Gene Therapy 04/2005; 16(3):372-80. · 4.22 Impact Factor
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ABSTRACT: This study investigates gene therapy with human tissue kallikrein as a treatment for fructose-induced hypertension in rats. Hypertension was induced by addition of 10% fructose to drinking water. Fructose-fed rats also had increased serum insulin and triglycerides, decreased urine osmolarity, increased urine volume and endothelin-1, and increased aortic endothelin-1, endothelin-A receptor, and angiotensin II receptor type 1 mRNA levels. Fructose-induced hypertensive and control rats were injected intravenously with a construct containing the human tissue kallikrein cDNA. Two weeks after injection of hypertensive rats, systolic blood pressure and serum insulin levels normalized, urine osmolarity increased, urine endothelin-1 levels decreased, and aortic endothelin-1, endothelin-A receptor, and angiotensin II receptor type 1 mRNA levels decreased. In contrast, injection of the human tissue kallikrein cDNA had minimal effect on blood pressure or insulin levels in control rats. These results suggest that gene therapy with human tissue kallikrein may have potential as a treatment for hypertension and associated insulin resistance. Moreover, our data suggest that the beneficial effects of human tissue kallikrein on these parameters are associated with changes in endothelin-1, endothelin-A receptor, and angiotensin II receptor type 1 expression.
Hypertension 11/2003; 42(5):1026-33. · 6.21 Impact Factor
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Gang Yuan,
Juanjuan Deng,
Tao Wang, Chunxia Zhao,
Xizheng Xu,
Peihua Wang,
James W Voltz,
Matthew L Edin,
Xiao Xiao,
Lee Chao,
Julie Chao,
Xin A Zhang,
Darryl C Zeldin,
Dao Wen Wang
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