Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammation causes vascular dysfunction and perpetuates proatherosclerotic processes. We hypothesized that a broad panel of inflammatory biomarkers and single nucleotide polymorphisms in inflammatory genes is associated with vascular stiffness. We assessed 12 circulating inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor-II) in relation to tonometry variables (central pulse pressure, mean arterial pressure, forward pressure wave, reflected pressure wave, carotid-femoral pulse wave velocity, and augmentation index) measured in 2409 Framingham Heart Study participants (mean age: 60 years; 55% women; 13% ethnic/racial minorities). Single nucleotide polymorphisms (n=2195) in 240 inflammatory candidate genes were related to tonometry measures in 1036 white individuals. In multivariable analyses, biomarkers explained <1% of any tonometry measure variance. Applying backward elimination, markers related to tonometry (P<0.01) were as follows: tumor necrosis factor receptor-II (inversely) with mean arterial pressure; C-reactive protein (positively) and lipoprotein-associated phospholipase-A2 (inversely) with reflected pressure wave; and interleukin-6 and osteoprotegerin (positively) with carotid-femoral pulse wave velocity. In genetic association analyses, lowest P values (false discovery rate <0.50) were observed for rs10509561 (FAS), P=6.6x10(-5) for central pulse pressure and rs11559271 (ITGB2), P=1.1x10(-4) for mean arterial pressure. These data demonstrate that, in a community-based sample, circulating inflammatory markers tumor necrosis factor receptor-II (mean arterial pressure), C-reactive protein, lipoprotein-associated phospholipase-A2 activity (reflected pressure wave), interleukin-6, and osteoprotegerin (carotid-femoral pulse wave velocity) were significantly but modestly associated with measures of arterial stiffness and wave reflection. Additional studies are needed to determine whether variation in inflammatory marker genes is associated with tonometry measures.
Hypertension 2008 Jun
PMID:Relations of inflammatory biomarkers and common genetic variants with arterial stiffness and wave reflection. 1842 90

Hypertension and Type 2 diabetes are co-morbid diseases that lead to the development of nephropathy. sEH (soluble epoxide hydrolase) inhibitors are reported to provide protection from renal injury. We hypothesized that the sEH inhibitor AUDA [12-(3-adamantan-1-yl-ureido)-dodecanoic acid] protects the kidney from the development of nephropathy associated with hypertension and Type 2 diabetes. Hypertension was induced in spontaneously diabetic GK (Goto-Kakizaki) rats using AngII (angiotensin II) and a high-salt diet. Hypertensive GK rats were treated for 2 weeks with either AUDA or its vehicle added to drinking water. MAP (mean arterial pressure) increased from 118+/-2 mmHg to 182+/-20 and 187+/-6 mmHg for vehicle and AUDA-treated hypertensive GK rats respectively. AUDA treatment did not alter blood glucose. Hypertension in GK rats resulted in a 17-fold increase in urinary albumin excretion, which was decreased with AUDA treatment. Renal histological evaluation determined that AUDA treatment decreased glomerular and tubular damage. In addition, AUDA treatment attenuated macrophage infiltration and inhibited urinary excretion of MCP-1 (monocyte chemoattractant protein-1) and kidney cortex MCP-1 gene expression. Taken together, these results provide evidence that sEH inhibition with AUDA attenuates the progression of renal damage associated with hypertension and Type 2 diabetes.
 ...
PMID:Administration of a substituted adamantyl urea inhibitor of soluble epoxide hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats. 1845 44

Clinical and experimental studies have provided evidence suggesting that statins exert renoprotective effects. To investigate the mechanisms by which statins may exert renoprotection, we utilized the hypertensive Dahl salt-sensitive (DS) rat model, which manifests cardiovascular and renal injury linked to increased angiotensin II-dependent activation of NADPH oxidase and decreased nitric oxide (NO) bioavailability. DS rats given high salt diet (4% NaCl) for 10 wk exhibited hypertension [systolic blood pressure (SBP) 200 +/- 8 vs. 150 +/- 2 mmHg in normal salt diet (0.5% NaCl), P < 0.05], glomerulosclerosis, and proteinuria (158%). This was associated with increased renal oxidative stress demonstrated by urinary 8-F(2alpha)-isoprostane excretion and NADPH oxidase activity, increased protein expression of transforming growth factor (TGF)-beta (63%) and fibronectin (181%), increased mRNA expression of the proinflammatory molecules monocyte chemoattractant protein-1 (MCP-1) and lectin-like oxidized LDL receptor-1 (LOX-1), as well as downregulation of endothelial NO synthase (eNOS) activity (-44%) and protein expression. Return to normal salt had no effect on SBP or any of the measured parameters. Atorvastatin (30 mg.kg(-1).day(-1)) significantly attenuated proteinuria and glomerulosclerosis and normalized renal oxidative stress, TGF-beta1, fibronectin, MCP-1 and LOX-1 expression, and eNOS activity and expression. Atorvastatin-treated rats showed a modest reduction in SBP that remained in the hypertensive range (174 +/- 8 mmHg). Atorvastatin combined with removal of high salt normalized SBP and proteinuria. These findings suggest that statins mitigate hypertensive renal injury by restoring the balance among NO, TGF-beta1, and oxidative stress and explain the added renoprotective effects observed in clinical studies using statins in addition to inhibitors of the renin-angiotensin system.
 ...
PMID:Renoprotection by statins is linked to a decrease in renal oxidative stress, TGF-beta, and fibronectin with concomitant increase in nitric oxide bioavailability. 1846 18

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a membrane protein that can support the binding, internalization, and proteolytic degradation of oxidized low-density lipoprotein. The LOX-1 expression increases in the neointima after balloon injury. To develop an efficient compound to inhibit LOX-1, we designed and synthesized a novel gene silencer pyrrole-imidazole (PI) polyamide targeting the rat LOX-1 gene promoter (PI polyamide to LOX-1) to the activator protein-1 binding site. We examined the effects of PI polyamide to LOX-1 on the LOX-1 promoter activity, the expression of LOX-1 mRNA and protein, and neointimal hyperplasia of the rat carotid artery after balloon injury. PI polyamide to LOX-1 significantly inhibited the rat LOX-1 promoter activity and decreased the expression of LOX-1 mRNA and protein. After balloon injury of the arteries, PI polyamide to LOX-1 was incubated for 10 minutes. Fluorescein isothiocyanate-labeled PI polyamide was distributed to almost all of the nuclei in the injured artery. PI polyamide to LOX-1 (100 microg) significantly inhibited the neointimal thickening by 58%. PI polyamide preserved the re-endothelialization in the injured artery. PI polyamide significantly inhibited the expression of LOX-1, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9 mRNAs in the injured artery. The synthetic PI polyamide to LOX-1 decreased the expression of LOX-1 and inhibited neointimal hyperplasia after arterial injury. This novel gene silencer PI polyamide to LOX-1 is, therefore, considered to be a feasible agent for the treatment of in-stent restenosis.
Hypertension 2008 Jul
PMID:Novel gene silencer pyrrole-imidazole polyamide targeting lectin-like oxidized low-density lipoprotein receptor-1 attenuates restenosis of the artery after injury. 1851 43

Angiotensin II (Ang II)-induced hypertension is associated with an inflammatory response that may contribute to the development of target organ damage. We tested the hypothesis that, in Ang II-induced hypertension, CC chemokine receptor 2 (CCR2) activation plays an important role in the development of renal fibrosis, damage, and dysfunction by causing oxidative stress, macrophage infiltration, and cell proliferation. To test this hypothesis, we used CCR2 knockout mice (CCR2-/-). The natural ligand of CCR2 is monocyte chemoattractant protein-1, a chemokine important for macrophage recruitment and activation. CCR2-/- and age-matched wild-type (CCR2+/+) C57BL/6J mice were infused continuously with either Ang II (5.2 ng/10 g per minute) or vehicle via osmotic minipumps for 2 or 4 weeks. Ang II infusion caused similar increases in systolic blood pressure and left ventricular hypertrophy in both strains of mice. However, in CCR2-/- mice with Ang II-induced hypertension, oxidative stress, macrophage infiltration, albuminuria, and renal damage were significantly decreased, and glomerular filtration rate was significantly higher than in CCR2+/+ mice. We concluded that, in Ang II-induced hypertension, CCR2 activation plays an important role in the development of hypertensive nephropathy via increased oxidative stress and inflammation.
Hypertension 2008 Aug
PMID:Role of inflammation in the development of renal damage and dysfunction in angiotensin II-induced hypertension. 1883 21

Essential hypertension is idiopathic although it is accepted as a complex polygenic trait with underlying genetic components, which remain unknown. Our supposition is that hypertension involves activation of the sympathetic nervous system. One pivotal region controlling arterial pressure set point is nucleus tractus solitarii (NTS). We recently identified that pro-inflammatory molecules, such as junctional adhesion molecule-1 (JAM-1), were over expressed in endothelial cells of the microvasculature supplying the NTS in an animal model of human hypertension (the spontaneously hypertensive rat) compared to normotensive Wistar-Kyoto rats (WKY). Over expression of JAM-1 in NTS of WKY rats was pro-hypertensive and induced leukocyte adherence to the microvasculature. Since leukocyte adhesion causes cytokine release, we found expression of monocyte chemoattractant protein-1 (MCP-1) was higher in the NTS of SHR while inter-leukin-6 (IL-6) was lower compared to the WKY rat. Inflammation of the brainstem microvasculature may increase vascular resistance within the brainstem. High brainstem vascular resistance and its inflammation may release pathological paracrine signaling molecules affecting central neural cardiovascular activity conducive to neurogenic hypertension.
 ...
PMID:Is neurogenic hypertension related to vascular inflammation of the brainstem? 1858 82

Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. Since the brainstem structure--the nucleus of the solitary tract (NTS)--is a pivotal region for regulating the set-point of arterial pressure, we proposed a role for it in the development of primary hypertension. Using microarray and real-time RT-PCR, we have recently identified that some pro-inflammatory molecules, such as junctional adhesion molecule-1 (JAM-1; a leukocyte/platelet adhesion molecule), were over expressed in endothelial cells in the NTS of an animal model of human essential hypertension--the spontaneously hypertensive rat (SHR) compared to normotensive Wistar Kyoto rats (WKY). Adenoviral mediated over expression of JAM-1 in NTS of WKY rats produced both hypertension and localized leukocyte adherence to the microvasculature. With a known effect of leukocyte adhesion causing cytokine release, we predicted differences in the level of gene expression of cytokines in the NTS of SHR relative to WKY. Gene expression of monocyte chemoattractant protein-1 (MCP-1) was higher in the NTS of SHR while inter-leukin-6 (IL-6) was lower in the NTS of SHR compared to the WKY. Because both inflammatory molecules are known to affect neural functions, our data suggest that the microvasculature of NTS of the SHR exhibits a specific inflammatory state. We propose a new hypothesis that as a consequence of enhanced expression of leukocyte adhesion molecules within the microvasculature of NTS there is a specific inflammatory response that leads to cardiovascular autonomic dysfunction contributing to neurogenic hypertension.
 ...
PMID:Specific inflammatory condition in nucleus tractus solitarii of the SHR: novel insight for neurogenic hypertension? 1872 65

The transient receptor potential vanilloid (TRPV1) channels expressed in sensory afferent fibers innervating the heart may be activated by protons or endovanilloids released during myocardial ischemia (MI), leading to angina. Although our previous in vitro data indicate that TRPV1 activation may preserve cardiac function after ischemia-reperfusion injury, the underlying mechanisms are largely unknown. To test the hypothesis that TRPV1 modulates inflammatory and early remodeling processes to prevent cardiac functional deterioration after myocardial infarction, TRPV1-null mutant (TRPV1(-/-)) and wild-type (WT) mice were subjected to left anterior descending coronary ligation or sham operation. The infarct size was greater in TRPV1(-/-) than in WT mice (P<0.001) 3 days after MI, and the mortality rate was higher in TRPV1(-/-) than in WT mice (P<0.05) 7 days after MI. The levels of plasma cardiac troponin I; cytokines, including tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6; chemokines, including monocyte chemoattractant protein-1 and macrophage inflammatory protein-2; and infiltration of inflammatory cells, including neutrophils, macrophages, and myofibroblasts; as well as collagen contents, were greater in TRPV1(-/-) than in WT mice (P<0.05) in the infarct area on days 3 and 7 after MI. Changes in left ventricular geometry led to increased end-systolic and -diastolic diameters and reduced contractile function in TRPV1(-/-) compared with WT mice. These data show that TRPV1 gene deletion results in excessive inflammation, disproportional left ventricular remodeling, and deteriorated cardiac function after MI, indicating that TRPV1 may prevent infarct expansion and cardiac injury by inhibiting inflammation and abnormal tissue remodeling.
Hypertension 2009 Feb
PMID:Transient receptor potential vanilloid gene deletion exacerbates inflammation and atypical cardiac remodeling after myocardial infarction. 1911 47

Several epidemiological studies show that obesity is a major primary health problem and an independent risk factor for type II diabetes, cardiovascular diseases, and hypertension. Increasing evidence indicates that altered secretion of adipocytokines such as adiponectin, tumor necrosis factor alpha, monocyte chemoattractant protein-1 and free fatty acids are contributing factors to insulin resistance in obese states. Especially, visceral obesity is strongly associated with insulin resistance rather than subcutaneous adipose tissue. Body weight reduction by lifestyle intervention is reported to reduce the risk for developing type II diabetes.
 ...
PMID:[Obesity as risk for developing diabetes]. 1920 9

1. In the present study, we determined the role of hypertension, oxidative stress and inflammation on kidney damage in a rodent model of obesity and diabetes. Hypertension was induced in male obese (db/db) mice and lean (db/m) mice by implantation of deoxycorticosterone acetate (DOCA) pellets and mice were allowed to drink water containing 1% salt. Mice were divided into six groups as follows: obese and lean control, obese and lean 1% salt (salt) and obese and lean DOCA plus 1% salt (DOCA-salt). 2. Blood pressure was significantly increased in lean and obese DOCA-salt groups relative to their respective controls; however, there was no difference in blood pressure between the lean and obese control and salt groups. Urinary 8-isoprostane was increased in obese control compared with lean control mice (1464 +/- 267 vs 493 +/- 53 pg/micromol creatinine, respectively) and this elevation was further increased in the obese DOCA-salt treated mice (2430 +/- 312 pg/micromol creatinine). Urinary monocyte chemoattractant protein-1 excretion and CD68-positive cells were also increased in both obese and lean DOCA-salt groups compared with their respective controls. Furthermore, DOCA-salt treatment increased collagen IV excretion in both obese and lean mice compared with controls, but there was no difference between obese and lean DOCA-salt groups. Urinary albumin excretion was significantly increased in the obese compared with the lean DOCA-salt mice (507 +/- 160 vs 202 +/- 48 microg/day, respectively). 3. These data suggest that obese DOCA-salt hypertensive mice exhibit greater renal injury than lean DOCA-salt hypertensive mice in a manner independent of blood pressure and that this renal injury is associated with obesity related pre-existing renal oxidative stress.
 ...
PMID:Obesity induced renal oxidative stress contributes to renal injury in salt-sensitive hypertension. 1920 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>