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

A 24-year-old woman with overlapping features of sclerodermia sine scleroderma and systemic lupus erythematosus (SLE) presented with rapidly accelerating hypertension accompanied by neuropsychological deficits and tonic-clonic seizures. Kidney biopsy showed severe intimal hyperplasia of small renal arteries but no glomerulonephritis. Following treatment with ACE inhibitor, prednisolone and cyclophosphamide complete remission was achieved with minimal brain damage and normal kidney function. Anti-RNA polymerase I, II and III antibodies have remained positive during follow-up for 2 years, suggesting a linkage with the underlying pathogenetic pathway.
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PMID:Renal crisis in asclerodermic scleroderma--lupus overlap syndrome. 1178 81

The recent discovery that sporadic and familial primary pulmonary hypertension can be associated with germline mutations of genes encoding receptor members of the transforming growth factor-beta family has focused much attention on cytokines and growth factors in pulmonary vascular disorders. Production of several cytokines has been demonstrated in severe pulmonary arterial hypertension, emphasizing the possible influence of inflammatory mechanisms in this condition. Moreover, perivascular inflammatory cell infiltrates composed of macrophages and lymphocytes have been detected in plexiform lesions of primary pulmonary hypertension. Chemokine RANTES is an important chemoattractant for monocytes and T cells. We therefore hypothesize that chemokine RANTES promotes cell recruitment in the lungs of patients displaying severe pulmonary arterial hypertension. Reverse transcriptase polymerase chain reaction demonstrated elevated RANTES mRNA expression in 10 lung samples from patients with severe pulmonary arterial hypertension, as compared with seven control subjects. In situ hybridization and immunohistochemistry confirmed that endothelial cells were the major source of RANTES within the pulmonary artery wall of the patients. Serial sections analysis showed that RANTES expression was associated with CD45+ inflammatory cell infiltrates. These results support the concept that inflammatory mechanisms play a role in the natural history of pulmonary arterial hypertension.
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PMID:Chemokine RANTES in severe pulmonary arterial hypertension. 1185 Mar 48

In view of the ongoing controversy of cardiorenal safety of selective COX-2 inhibitors (coxibs), the present study was designed to examine the effects of 2 different coxibs, celecoxib and rofecoxib, compared with a traditional NSAID, diclofenac, and placebo on renal morphology and function in salt-sensitive hypertension. Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were fed with NaCl-enriched diet (4% NaCl) for 8 weeks. Diclofenac (DS-diclofenac), rofecoxib (DS-rofecoxib), celecoxib (DS-celecoxib), or placebo was added to chow from weeks 6 to 8. Immunostaining for monocytes/macrophages (ED1) and cytotoxic T lymphocytes (CD8) was performed. In addition, renal morphology and proteinuria were assessed. Renal cortex mRNA was isolated for determination of COX-2, eNOS, and CRP mRNA by real-time reverse-transcriptase polymerase chain reaction. Untreated hypertensive animals showed glomerular injury including collapsing glomerulopathy, mesangial sclerosis, mesangiolysis, extracapillary proliferation, protein drops, and an especially high grade of glomerulosclerosis (P<0.05 versus DR-placebo) and CD8-positive and ED1-positive cells (P<0.01 versus DR-placebo), which was improved by celecoxib but not by diclofenac and rofecoxib. C-reactive protein mRNA in renal cortex was increased in DS-placebo animals (P<0.05 versus DR-placebo) and normalized by celecoxib (P<0.05 versus DS-placebo), whereas eNOS mRNA was decreased in the DS-rofecoxib group (P<0.05 versus DR-placebo, DS-celecoxib, and DS-diclofenac). Proteinuria was observed in hypertensive animals (P<0.0001 versus DR-placebo), increased by rofecoxib (P<0.05 versus DS-placebo), and normalized by celecoxib (P=0.0015 versus DS-placebo). This head-to-head comparison of selective and nonselective COX inhibitors demonstrates differential effects of coxibs on renal morphology and function in salt-dependent hypertension.
Hypertension 2005 Feb
PMID:Selective COX-2 inhibitors and renal injury in salt-sensitive hypertension. 1562 40

Despite intensive investigation, the molecular mechanism by which the angiotensin II type 2 (AT2) receptor exerts its cellular and physiological actions remains elusive. In the present study, we have used microarray expression analysis to identify genes whose expression was regulated by this receptor and to determine its cellular consequences. Lentiviral vector was used to express the AT2 receptor in human coronary artery endothelial cells (HCAECs), followed by analysis of expression profiles. We observed approximately 5224 genes regulated in an AT2 receptor ligand-independent manner in HCAECs expressing the AT2 receptor. In addition, 1235 genes were differentially expressed in response to the AT2 receptor-specific ligand, CGP42112A. Validity of the expression profiles was demonstrated by real-time reverse-transcriptase polymerase chain reaction quantitation of 5 genes. Because some of these genes could be linked to the regulation of extracellular matrix association, we studied the effect of the AT2 receptor on cell migration. Expression of the AT2 receptor resulted in a 2-fold inhibition of HCAEC migration. Taken together, these observations demonstrate that the AT2 receptor regulates expression of genes relevant to cell migration, protein processing, intracellular signaling, and DNA repair in both ligand-dependent and ligand-independent manners.
Hypertension 2005 Apr
PMID:Angiotensin II type 2 receptor-mediated gene expression profiling in human coronary artery endothelial cells. 1571 Jul 80

Ramipril improves cardiovascular outcome in patients with peripheral arterial disease; however, the precise mechanisms of benefit remain to be elucidated. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined. In addition, we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture. Forty patients with peripheral arterial disease were randomized to receive ramipril, 10 mg once daily or placebo for 24 weeks. Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index (carotid tonometry and Doppler velocimetry), and regionally via carotid-femoral pulse wave velocity. Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10+/-0.02 mL/mm Hg, (P<0.001, all probability values relative to placebo) and reduced pulse wave velocity by 1.7+/-0.2 m/s (P<0.001), augmentation index by 4.1+/-0.3% (P<0.001), and systolic blood pressure by 5+/-1 mm Hg (P<0.001). Ramipril did not reduce mean arterial pressure significantly compared with placebo (P=0.59). In cell culture, ramiprilat decreased collagen deposition by >50% and increased elastin and fibrillin-1 deposition by >3- and 4-fold respectively (histochemistry and immunohistochemistry). Fibrillin-1 gene expression was increased 5-fold (real-time reverse-transcriptase polymerase chain reaction). Ramiprilat also reduced gene and protein (Western) expression of both matrix metalloproteinase (MMP)-2 and MMP-3. In conclusion, ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation, which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease.
Hypertension 2005 Jun
PMID:Ramipril reduces large-artery stiffness in peripheral arterial disease and promotes elastogenic remodeling in cell culture. 2665 6

The prognosis of systemic sclerosis depends chiefly on the extent of the skin lesions, which correlates with the severity of the cardiovascular, pulmonary, and renal manifestations. An erythrocyte sedimentation rate greater than 15-25 mm/h or a hemoglobin level lower than 12.5-11 g/dl is associated with a 2.5- to 3-fold increase in mortality. Anticentromere antibodies are associated with delayed pulmonary hypertension, anti-topoisomerase I antibodies (Scl 70) with interstitial lung disease, and anti-RNA polymerase III antibodies with renovascular hypertension. The risk of death is directly related to the autoantibody pattern. For instance, in a study of 1432 cases from the Pittsburgh Scleroderma Databank, 10-year survival among patients with limited cutaneous disease was 88% in the group with anti-U1-RNP, 75% in the group with anticentromere antibodies, 72% in the group with anti-PmScl, and 65% in the group with anti-Th/To. Ten-year survival in patients with diffuse cutaneous disease was 64% with anti-topoisomerase antibodies, 61% with anti-U3-RNP, and 75% with anti-RNA polymerase III. Several prognostic markers are also available for predicting the risk of organ involvement. For instance, serum levels of KL-6, surfactant proteins SP-A and SP-D, the collagen peptide PIIINP, and homocysteine are associated with the risk of fibrosing alveolitis. Serum levels of CD40L and NP-ProBNP, circulating endothelial cells, and serum anticardiolipin titers correlate with the risk of arterial hypertension. Serum VCAM1 and markers for oxidative stress such as carboxyl terminus residues predict the risk of vascular disease. Other serum markers for organ involvement are under study, although their predictive performance remains to be evaluated.
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PMID:Prognostic markers for systemic sclerosis. 1679 48

We have encountered a 68-year-old Japanese woman with limited cutaneous systemic sclerosis who developed de novo onset of accelerated hypertension and renal dysfunction; thus we diagnosed scleroderma renal crisis. Anticentromere antibody alone was identified, and not anti-DNA topoisomerase I antibody, anti-RNA polymerase antibodies, anti-Th/To antibodies, or antiribonucleoprotein antibodies, even with use of immunoprecipitation assay. She was successfully treated with angiotensin-converting enzyme inhibitor. This case, scleroderma renal crisis with detection of anticentromere antibody, is thought to be extremely uncommon.
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PMID:Scleroderma renal crisis in a patient with anticentromere antibody-positive limited cutaneous systemic sclerosis. 1703 13

Scleroderma (SSc) renal crisis has been reported to be associated with anti-RNA polymerase I and III (RNAP I/III) antibodies in Caucasians and the Japanese. However, no report is available for Korean SSc patients. Here, we describe the case of a 65-yr-old female SSc patient who developed renal crisis and whose serum contained anti-RNAP I/III antibodies. She was finally diagnosed as having diffuse cutaneous SSc based on skin thickening proximal to the elbows and knees. Sudden hypertension, oliguria, and pulmonary edema were features of her renal crisis. Despite the use of captopril and adequate blood pressure control, her renal function deteriorated. Subsequent renal biopsy findings showed severe fibrinoid necrosis with luminal obliteration in interlobar arteries and arterioles consistent with SSc renal crisis. Serum anti-RNAP I/III antibodies were detected by radioimmunoprecipitation. This is the first report of a renal crisis in a Korean SSc patient with RNAP I/III antibodies.
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PMID:A case of renal crisis in a Korean scleroderma patient with anti-RNA polymerase I and III antibodies. 1717

The use of highly active antiretroviral therapy (HAART) in HIV-infected patients has been associated with the development of risk factors for cardiovascular diseases (CD) including dyslipidemia and insulin resistance, hypertriglyceridemia being the most frequent metabolic disturbance in these patients. Fibrates are indicated when hypertriglyceridemia is accentuated and persists for over six months. We evaluated the efficacy and safety of bezafibrate for the treatment of hypertriglyceridemia in HIV-infected individuals on HAART. All patients received 400mg/day of bezafibrate and were evaluated three times: Mo (pre-treatment), M1 (one month after treatment), and M2 (six months after treatment). Fifteen adult individuals, eight males and seven females with mean age = 41.2 +/- 7.97 years and triglyceride serum levels > 400mg/dL were included in the study. Smoking, alcohol ingestion and sedentarism rates were 50%, 6.66% and 60%, respectively. Family history of CD, hypertension and diabetes mellitus was reported in 33.3%, 40% and 46.7% of the cases, respectively, while dyslipidemia was reported by only 13.3%. More than half of the patients were using a protease inhibitor plus a nucleotide analog transcriptase inhibitor. Eutrophy and tendency toward overweight were observed at all three study time points. There were significant reductions in triglyceride serum levels from Mo to M1 and from Mo to M2. No significant changes were observed in the serum levels of creatine phosphokinase, hepatic enzymes, CD4+, CD8+ and viral load. Therefore, bezafibrate seems to be safe and effective for the reduction of hypertriglyceridemia in HIV-infected patients on HAART.
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PMID:Bezafibrate for the treatment of hypertriglyceridemia in HIV1-infected patients on highly active antiretroviral therapy. 1756 45

TATA-binding protein (TBP) is the first basal factor that recognizes and binds a TATA box on TATA-containing gene promoters transcribed by RNA polymerase II. Data available in the literature are indicative of admissible variability of the TATA box. The TATA box flanking sequences can influence TBP affinity as well as the level of basal and activated transcription. The possibility of mediated involvement in in vivo gene expression regulation of the TBP interactions with variant TATA boxes is supported by data on TATA box polymorphisms and associated human hereditary pathologies. A table containing data on TATA element polymorphisms in human gene promoters (about 40 mutations have been described), associated with particular pathologies, their short functional characteristics, and manifestation mechanisms of TATA-box SNPs is presented. Four classes of polymorphisms are considered: TATA box polymorphisms that weaken and enhance promoter, polymorphisms causing TATA box emergence and disappearance, and human virus TATA box polymorphisms. The described examples are indicative of the polymorphism-associated severe pathologies like thalassemia, the increased risk of hepatocellular carcinoma, sensitivity to H. pylori infection, oral cavity and lung cancers, arterial hypertension, etc.
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PMID:TATA box polymorphisms in human gene promoters and associated hereditary pathologies. 1926 66


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