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)

Adhesion molecules on the endothelial cell membrane play an important role in the pathogenesis of atherosclerosis. Levels of soluble forms of cell adhesion molecules are reportedly elevated in patients with peripheral artery vessel disease and in patients with an atherosclerotic aorta. The present study investigated the association of serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), and soluble P-selectin (sP-selectin) with coronary heart disease (CHD) and the extent of coronary atherosclerosis, and examined the influence of serum levels of lipids, lipoproteins and apolipoproteins (apo) in subjects with (n=52, M/F:43/9) and without (controls, n=40, M/F:25/15) angiographically proven coronary atherosclerosis. After controlling for age and gender, levels of sVCAM-1 (least squares mean +/- std error: 565+/-36 ng/ml vs 540+/-41 ng/ml, ns), sICAM-1 (261+/-17ng/ml vs 247+/-19ng/ml, ns), and sP-selectin (142+/-8ng/ml vs 149+/-10 ng/ml, ns) in patients with coronary atherosclerosis were not different from those in controls, as assessed by an analysis of covariance. After also adjusting for body mass index, hypertension, diabetes mellitus, and smoking by a multiple logistic function analysis, the association of sVCAM-1, sICAM-1, and sP-selectin with CHD was still not significant. Levels of sVCAM-1, sICAM-1, and sP-selectin were also not related to the extent of coronary atherosclerosis as judged by the number of stenosed vessels. However, inverse (p<0.05) relationships were observed between sVCAMs and serum levels of HDL3-cholesterol, apo A-II, and lipoprotein containing apo A-I and A-II, between sICAMs and levels of apo A-II and Lp A-I/A-II (Lp A-I/A-II), and between sP-selectin and lipoprotein containing only apo A-I. In conclusion, serum levels of soluble VCAM-1, ICAM-1, and P-selectin were not related to CHD or the extent of coronary atherosclerosis, but were inversely related to serum levels of high-density lipoprotein-related lipoproteins.
 ...
PMID:Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis. 1008 83

Coronary artery disease (CAD) is the leading cause of death in patients with end-stage renal disease (ESRD). Recent evidence suggests that the expression of Fas, a molecule implicated in the initiation of apoptosis in various cell types, is increased at sites of atherosclerotic plaques. However, the significance of plasma levels of the soluble form of Fas (sFas) and its ligand (sFas-L) as markers of atherosclerosis has yet to be defined. The present report is a cross-sectional analysis of baseline data from an ongoing prospective study designed to evaluate the role of sFas and sFas-L as markers of CAD in ESRD. We evaluated the association between plasma levels of sFas and sFas-L and evidence of CAD in a cohort of 107 chronic hemodialysis patients. Plasma levels of sFas were significantly greater (P = 0.04) among subjects with (n = 64) than without evidence of CAD (n = 43). Plasma levels of sFas-L were similar in both groups. Using multivariate analysis, sFas level was found to be independently associated with CAD (P = 0.01) after adjustment for classic risk factors for CAD (hyperlipidemia, diabetes, hypertension, and smoking), markers of inflammation (C-reactive protein [CRP], intercellular adhesion molecule 1), and other confounders. An increase of one quintile in plasma concentration of sFas was associated with an odds ratio for CAD of 1.64 (95% confidence interval, 1.11 to 2.41). Models that incorporated sFas were significantly better at identifying patients with CAD than models limited to classic risk factors for atherosclerosis, alone (P = 0.008) or in combination with CRP levels (P = 0.006). In summary, increased plasma levels of sFas are associated with CAD in stable patients with ESRD. These results suggest that sFas may represent a novel and independent marker of CAD.
 ...
PMID:Soluble Fas is a marker of coronary artery disease in patients with end-stage renal disease. 1172 60

The attachment of monocytes and lymphocytes to endothelial cells, which initiates atherosclerosis, arises under the influence of adhesion molecules. The preclinical phase of this disease lasts many decades, and this provides an opportunity for the presymptomatic detection of high-risk subjects. We evaluated levels of the adhesion molecules: sICAM-1 (soluble intercellular adhesion molecule 1), sVCAM-1 (soluble vascular adhesion molecule 1), sE selectin, sP selectin, and sL selectin in children with atherosclerosis risk factors (n = 123, mean age 15.1 years) (obese [n = 17], hypertensive [n = 25], obese with hypertension [n = 30], type 1 diabetic [n = 51]). Twenty-seven healthy children formed the control group, mean age 15.2 years. sICAM-1 was higher in the study group compared with control (314.1 +/- 61 vs 264.9 +/- 55 ng/mL, P < .01). The same was found for sVCAM-1 (513.7 +/- 187 vs 407.9 +/- 76 ng/mL, P < .05) and E selectin (86.04 +/- 33.6 vs 62.1 +/- 20.3 ng/mL, P < .01). sP-selectin and sL-selectin levels were not different compared with controls. E selectin correlated with body mass index (BMI; r = 0.18, P = .03), total cholesterol (r = 0.2, P = .016), and triglycerides (r = 0.22, P = .008). sICAM-1 correlated with BMI (r = 0.19, P = .019) and systolic blood pressure (r = 0.13, P = .045). In multiple linear regression analysis, sE selectin was found to be associated with triglycerides (R2 = 0.29, P = .045), sICAM-1 dependent on BMI (R2 = 0.58, P = .047), and sVCAM-1 dependent on total cholesterol (R2 = 0.51, P = .006). Elevated concentrations of sICAM-1, sVCAM-1, and E selectin were found in obese, hypertensive, and diabetic children. We conclude that endothelial activation appears in these children, and adhesion molecules are related to the earliest stages of atherosclerosis.
 ...
PMID:Soluble adhesion molecules (sICAM-1, sVCAM-1) and selectins (sE selectin, sP selectin, sL selectin) levels in children and adolescents with obesity, hypertension, and diabetes. 1609 51

It is hypothesized that preeclampsia is caused by factors from the placenta that induce endothelial cell activation. Trophoblasts are cells that may be shed from the placenta, then deported in the maternal blood, and finally become trapped in the pulmonary capillaries. The ultimate fate of deported trophoblasts is unknown, but to prevent clogging of the pulmonary circulation they must be cleared from the capillary beds. We examined the hypothesis that endothelial cells phagocytose deported trophoblasts and also examined the consequent effects of the trophoblasts on endothelial cells. Fluorescently labeled trophoblast-derived choriocarcinoma cells were induced to become apoptotic or necrotic and exposed to endothelial cell monolayers. Confocal microscopy demonstrated uptake of both apoptotic and necrotic trophoblasts, and this phagocytosis could be inhibited by cytochalasin B. Phagocytosis of necrotic but not apoptotic trophoblasts induced increased endothelial intercellular adhesion molecule 1 (ICAM-1) expression, as well as increased adhesion of monocytes to endothelial cell monolayers. Inhibiting the phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase pathways blocked both expression of ICAM-1 and phagocytosis, whereas inhibition of the P42/44 mitogen-activated protein kinase pathway blocked only ICAM-1 expression. This work suggests that endothelial cells can phagocytose deported trophoblasts and that the mechanism of trophoblast death (apoptotic or necrotic) could have major effects on the maternal vascular response to shed trophoblasts.
Hypertension 2006 Jan
PMID:Phagocytosis of necrotic but not apoptotic trophoblasts induces endothelial cell activation. 1634 69

Hypertension is a major risk factor for atherosclerotic cardiovascular disease. Selectins, cell-surface adhesion molecules involved in leukocyte rolling and attachment to the vascular endothelium, play a role in the initiation of atherosclerosis. We investigated whether or not serum levels of soluble adhesion molecules are elevated in patients with essential hypertension (EH) and examined whether antihypertensive therapy lowers such levels. Twenty-one patients who had untreated mild to moderate EH without diabetes mellitus, hyperlipidemia, or obesity were recruited at a clinic for hypertensive patients. Blood pressure was measured, and the serum levels of soluble E-selectin, P-selectin, L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular-cell adhesion molecule 1 (VCAM-1) were determined by enzyme-linked immunosorbent assays before and after 12, 24, and 53 weeks of antihypertensive treatment with benidipine, a long-acting calcium channel blocker, given at a dose of 6 mg/day for 53 weeks. As a control, 21 age- and sex-matched patients without hypertension were studied. Serum E- and P-selectin levels were significantly higher in the subjects with EH than in the controls (p < 0.01). There were no differences in serum levels of soluble L-selectin, VCAM-1, or ICAM-1 levels between the patients with EH and the controls. Treatment with benidipine decreased the elevated blood pressure over a 53-week study period (mean blood pressure: 119.8 +/- 6.5 mmHg at baseline, 101.0 +/- 5.9 mmHg at 12 weeks, 98.6 +/- 7.3 mmHg at 24 weeks, and 93.9 +/- 5.5 mmHg at 53 weeks). Serum levels of soluble E- and P-selectin decreased after the initiation of benidipine treatment and correlated with diastolic blood pressure. Serum levels of soluble L-selectin, VCAM-1, and ICAM-1 did not change significantly during the period of benidipine treatment. Benidipine treatment reduced the content of P-selectin in the platelets from patients with EH, as determined by Western blot analysis. In conclusion, decreased blood pressure may reduce the rate of progression of atherosclerosis by affecting the expression of E- and P-selectin in the endothelium, the platelets, or both. Benidipine may be protective against vascular damage in people with hypertension, not only by lowering blood pressure, but also by inhibiting the expression of selectins.
 ...
PMID:Elevation of serum soluble E- and P-selectin in patients with hypertension is reversed by benidipine, a long-acting calcium channel blocker. 1655 75

Inhibition of the renin-angiotensin system reportedly exerts potent antiatherogenic effects by reducing vascular inflammation. We tested the hypothesis that pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, further reduces vascular inflammation in patients receiving angiotensin II receptor blockers. Patients with hypertension who had developed type 2 diabetes mellitus were randomly assigned to receive either pioglitazone (15 mg/d, n = 20) or voglibose, an alpha-glucosidase inhibitor (0.6 mg/d, n=19) for 6 months, and changes in their serum concentrations of C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were monitored. Pioglitazone, but not voglibose, reduced CRP levels within 1 month (-51%+/-7%, mean+/-SEM; P<.001). C-reactive protein levels were decreased after 6 months of treatment with either pioglitazone or voglibose, with the former being more effective (-57%+/-8% vs -9%+/-18%; P<.05). The levels of ICAM-1 and VCAM-1 were significantly reduced after 1 month of pioglitazone therapy (-9%+/-3% and -8%+/-3%, respectively; both P<.05), with the beneficial effects persisting throughout the study period. In contrast, the levels of ICAM-1 and VCAM-1 were not altered during the study period in patients on voglibose. There was no correlation between the reduction of hemoglobin A1c and that of CRP, ICAM-1, or VCAM-1. These results suggest that augmentation with pioglitazone further reduces vascular inflammation in patients with hypertension and diabetes who are receiving angiotensin II receptor blockers. This may contribute to the reduction of cardiovascular events in this at-risk population.
 ...
PMID:Pioglitazone produces rapid and persistent reduction of vascular inflammation in patients with hypertension and type 2 diabetes mellitus who are receiving angiotensin II receptor blockers. 1737 17

Hyperglycemia-induced oxidative stress plays a crucial role in the pathogenesis of vascular complications in diabetes. Although some clinical evidences suggest the use of an antioxidant reagent coenzyme Q10 in diabetes with hypertension, the direct effect of coenzyme Q10 on the endothelial functions has not been examined. In the present study, we therefore investigated the protective effect of coenzyme Q10 against high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVEC). HUVEC exposed to high glucose (30 mM) exhibited abnormal properties, including the morphological and biochemical features of apoptosis, overproduction of reactive oxygen species, activation of protein kinase Cbeta2, and increase in endothelial nitric oxide synthase expression. Treatment with coenzyme Q10 strongly inhibited these changes in HUVEC under high glucose condition. In addition, coenzyme Q10 inhibited high glucose-induced cleavage of poly(ADP-ribose) polymerase, an endogenous caspase-3 substrate. These results suggest that coenzyme Q10 prevents reactive oxygen species-induced apoptosis through inhibition of the mitochondria-dependent caspase-3 pathway. Moreover, consistent with previous reports, high glucose caused upregulation of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in HUVEC, and promoted the adhesion of U937 monocytic cells. Coenzyme Q10 displayed potent inhibitory effects against these endothelial abnormalities. Thus, we provide the first evidence that coenzyme Q10 has a beneficial effect in protecting against the endothelial dysfunction by high glucose-induced oxidative stress in vitro.
 ...
PMID:Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells. 1743 78

This study investigated whether subjects with permanent activated endothelium have altered soluble forms of intercellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1) postprandial response to a high-fat meal and whether this phenomenon is modulated by the nature of dietary fats. Twenty-eight hypertriglyceridemic (14 normotensives and 14 hypertensives) and 14 healthy male subjects were placed in a randomized and crossover design on diets enriched in refined olive oil (ROO) or high-palmitic sunflower oil (HPSO) for a 1-week lead-in period. Thereafter, subjects ate the corresponding fat-rich meal as a breakfast and underwent sampling hourly for 8 h. Plasma triglycerides (TG), sICAM-1 and sVCAM-1 were assayed. sICAM-1 and sVCAM-1 postprandial peak levels were significantly higher and occurred later in hypertriglyceridemic subjects (all P<.001) compared with healthy subjects. ROO meal resulted in smaller areas under the curve for sICAM-1 and sVCAM-1 in hypertriglyceridemic (normotensive and hypertensive) and healthy subjects compared to HPSO meal. Hypertension did not aggravate the postprandial response of TG, sICAM-1 and sVCAM-1. We conclude that the challenge of a meal with ROO appears to have a significant postprandial benefit on sICAM-1 and sVCAM-1 as surrogate markers of endothelial activation and vascular inflammation in healthy and more importantly in hypertriglyceridemic (normotensive and hypertensive) subjects.
 ...
PMID:A meal rich in oleic acid beneficially modulates postprandial sICAM-1 and sVCAM-1 in normotensive and hypertensive hypertriglyceridemic subjects. 1765 61

GTP cyclohydrolase 1 (GTPCH1) is the rate-limiting enzyme in de novo synthesis of tetrahydrobiopterin (BH4), an essential cofactor for endothelial NO synthase (eNOS) dictating, at least partly, the balance of NO and superoxide produced by this enzyme. The aim of this study was to determine the effect of acute inhibition of GTPCH1 on BH4, eNOS function, and blood pressure (BP) in vivo. Exposure of bovine or mouse aortic endothelial cells to GTPCH1 inhibitors (2,4-diamino-6-hydroxypyrimidine or N-acetyl-serotonin) or GTPCH1 small-interference RNA (siRNA) significantly reduced BH4 and NO levels but increased superoxide levels. This increase was abolished by sepiapterin (BH4 precursor) or N(G)-nitro-L-arginine methyl ester (nonselective NOS inhibitor). Incubation of isolated murine aortas with 2,4-diamino-6-hydroxypyrimidine or N-acetyl-serotonin impaired acetylcholine-induced endothelium-dependent relaxation but not endothelium-independent relaxation. Aortas from GTPCH1 siRNA-injected mice, but not their control-siRNA injected counterparts, also exhibited impaired endothelium-dependent relaxation. BH4 reduction induced by GTPCH1 siRNA injection was associated with increased aortic levels of superoxide, 3-nitrotyrosine, and adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), as well as a significantly elevated systolic, diastolic, and mean BP in C57BL6 mice. GTPCH1 siRNA was unable to elicit these effects in eNOS(-/-) mice. Sepiapterin supplementation, which had no effect on high BP in eNOS(-/-) mice, partially reversed GTPCH1 siRNA-induced elevation of BP in wild-type mice. In conclusion, GTPCH1 via BH4 maintains normal BP and endothelial function in vivo by preserving NO synthesis by eNOS.
Hypertension 2008 Sep
PMID:Acute inhibition of guanosine triphosphate cyclohydrolase 1 uncouples endothelial nitric oxide synthase and elevates blood pressure. 3226 10

Although Smad3 is a key mediator of fibrosis, the functional role of Smad3 in hypertensive cardiovascular disease remains unclear. The present study tested the hypothesis that angiotensin II may activate the transforming growth factor-beta/Smad3 pathway to mediate hypertensive cardiac remodeling in Smad3 knockout (KO) and wild-type mice by subcutaneous angiotensin II infusion and in the primary culture of Smad3 KO cardiac fibroblasts. Fourteen days after angiotensin II infusion, both Smad3 KO and wild-type mice developed equal levels of high blood pressure. However, hypertensive cardiac fibrosis and inflammation were developed in Smad3 wild-type but not in Smad3 KO mice. This was demonstrated by the findings that mice lacking Smad3 were protected against a fall in left ventricular ejection fraction (P<0.05), an increase in left ventricular mass (P<0.05), and the development of cardiac fibrosis and inflammation, including upregulation of transforming growth factor-beta1, connective tissue growth factor, collagen I/III, alpha-smooth muscle actin, interleukin 1beta, tumor necrosis factor-alpha, monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and an increase in macrophage and T-cell infiltration in left ventricular tissues (all P<0.01, respectively). Additional studies in vitro also revealed that angiotensin II-induced cardiac fibrosis and inflammation were prevented in Smad3 KO cardiac fibroblasts. Inactivation of both Smad3 and nuclear factor kappaB/p65 signaling pathways was a key mechanism by which Smad3 KO mice were protected from angiotensin II-mediated hypertensive cardiac remodeling. In conclusion, Smad3 plays an essential role in hypertensive cardiac remodeling. Results from this study suggest that targeting Smad3 may be a novel therapeutic strategy for hypertensive cardiovascular disease.
Hypertension 2010 May
PMID:Smad3 mediates cardiac inflammation and fibrosis in angiotensin II-induced hypertensive cardiac remodeling. 2023 19


1 2 3 4 Next >>