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)

New evidence about diabetic microangiopathy has enabled us to identify an integrated pathogenesis of diabetic complications, including classic metabolic pathways induced by hyperglycaemia, insulin-resistance, hyperinsulinaemia, hormonal alterations and growth factors. Oxidative stress is the most important cause of endothelial damage inducing leukocyte adhesion, altered coagulation and inflammation. Adhesion molecules are a marker of endothelial damage and a potential therapeutic target. Changes in the extracellular matrix induced by TGFbeta1 and lower levels of eparan-sulfate, increased thickness of basement membranes and loss of pericytes are early events of diabetic retinopathy and diabetic nephropathy. Capillary rarefaction produced by genetic factors or by fetal undernourishment contributes to the beginning of insulin-resistance and hypertension. Psychophysical tests, electroretinogram and evoked potentials show retinal functional alterations; fundoscopy and retinal fluorescein angiography show retinal anatomic alterations. The diagnosis of diabetic neuropathy is based not only on traditional neurological examination and electroneurograms, but also on neurothesiometry for sensory testing. Medical treatment of diabetic microangiopathy is based on control of glycaemia, lipemia and blood pressure using glytazones, ACE-inhibitors, angiotensin II receptor antagonists and statins. New knowledgeabout microangiopathy pathogenesis suggests potential drugs for its therapy (ruboxistaurin, AGE-inhibitors, angiopoietin-1 and anti-VEGF, etc.), not yet on sale.
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PMID:Diabetic microangiopathy: physiopathological, clinical and therapeutic aspects. 1791 58

The angiogenesis inhibitor bevacizumab, a VEGF antagonist, was approved in the European Union in August 2007 for the first-line therapy of inoperable, advanced or recurrent non-small-cell lung cancer, in combination with a platin-based chemotherapy regimen. Tumors with predominantly squamous-cell histology must be excluded. Two recent phase-III studies have shown that bevacizumab, combined with carboplatin and paclitaxel (E4599) or cisplatin and gemcitabine (AVAiL), significantly prolongs overall survival and/or progression-free survival. The most common adverse events during therapy with bevacizumab are hypertension and proteinuria - both are usually well manageable. By applying correct patient selection criteria the risk of pulmonary bleeding can be greatly reduced.
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PMID:[Bevacizumab in the first-line therapy of advanced NSCLC]. 1815 97

In metastatic colorectal cancer disease progression correlates with serum VEGF levels. The importance of VEGF in tumor-induced angiogenesis is well described in preclinical models. In this review we discuss the role of anti-VEGF therapy in combination with oxaliplatin-based chemotherapy for the treatment of metastatic colorectal cancer. A recent Phase III clinical trial in patients with metastatic colorectal cancer demonstrated the efficacy of FOLFOX4 in combination with bevacizumab, a recombinant humanized monoclonal antibody with high binding specificity for VEGF, to improve median overall survival when used as second-line therapy. The major adverse events associated with bevacizumab include grade III hypertension, bleeding and the risk of gastrointestinal perforation. Combining bevacizumab with oxaliplatin-based chemotherapy as first-line treatment for patients with metastatic colorectal cancer improves progression-free survival, as seen in the NO16966 and Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) studies, when compared with placebo and historical controls, respectively. Future research will need to focus on the mechanisms whereby bevacizumab enhances the benefit of chemotherapy to identify predictive markers that better define which patient populations will benefit the most from treatment.
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PMID:Bevacizumab and oxaliplatin-based chemotherapy in metastatic colorectal cancer. 1847 Oct 41

Diabetic retinopathy (DR) occurs in about 95% of patients with type 1 diabetes mellitus (DM) and in 60% of type 2 DM patients and it is the main cause of legal blindness in adult people. The aim of this manuscript was to review the main risk factors for DR. The major environmental risk factors are hyperglycemia, high blood pressure levels, and long-term duration of DM. However, not all patients will not develop DR, suggesting the presence of a genetic predisposition to DR, especially for severe forms of DR. Special strategies has been used to evaluate the genetic role in DR. Family studies shown that there is a familial aggregation of DR. Candidates genes have been studied (RAGE; VEGF; PPAR-delta; ICAM-1; ECA; ENPP 1; eNOS) and positive or negative associations with DR were demonstrated. Some chromosomes were also associated to DR in selected populations. Finally, genetic expression studies reinforce the association of candidate genes, or participation of others genes, with the presence of DR. DR is a common complication of DM and, along with non-genetic or environmental risk factors, the identification of genes related to DR could result in more specific and efficient DR treatment.
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PMID:[Diabetic retinopathy risk factors]. 1850 68

Axitinib is an oral inhibitor of the VEGF, PDGF and colony stimulating factor-1 receptor tyrosine kinases and is currently in development by Pfizer Inc for the potential treatment of various solid tumors. Phase II trials with this agent alone or in combination with chemotherapeutic drugs were reported in several types of malignancy, with activity observed in thyroid, pancreatic, lung, renal, breast and colorectal cancers, melanoma and other carcinomas. Although frequent side effects have included fatigue, hypertension, diarrhea, hand-foot syndrome and proteinuria, axitinib was well tolerated overall. Larger, randomized phase II/III studies were ongoing at the time of publication.
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PMID:Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. 1851 65

Anti-angiogenic therapies have a particular drug-related toxicity profile including hypertension, thrombosis, haemorrhages, and proteinuria. Moreover, patients treated by angiogenesis inhibitors present nasal symptoms including symptomatic rhinitis and epistaxis. For the first time, a new entity of "atrophic rhinitis" induced by angiogenesis inhibitors is described and revealed that angiogenesis inhibitors alter the differentiation of nasal epithelium. VEGF may act on epithelial cell proliferation and differentiation in nasal epithelium.
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PMID:Rhinitis and epistaxis in patients treated by anti-angiogenic therapy. 2044 Jun 35

Cardiac vessel density (beta-actin immunolabeling) and angiogenic capacity of coronary artery explants (culture in collagen gel) was determined in hypertrophied heart obtained by exercise training (10 wk) or ANG II infusion for 10 days. A group of rats received ANG II the last 10 days of training. The heart weight index was similarly elevated after exercise, and ANG II-hypertension compared with controls (3.16 +/- 0.09 and 3.11 +/- 0.11 vs. 2.68 +/- 0.08 mg/g, respectively), whereas tail cuff pressure (TCP) increased only in sedentary rats infused with ANG II. Vessel density was increased by 36% in trained rats and reduced by 30% in ANG II-infused rats. The number of sprouts generated by coronary rings was reduced by 50% in ANG II-infused rats and increased by 50% in exercise trained rats compared with controls (35 +/- 4 and 113 +/- 5 vs. 71 +/- 1 sprouts per ring, respectively). Exercise-training partly prevented the hypertensive effect of ANG II (TCP of 141 +/- 5 mmHg), whereas heart weight index (3.66 +/- 0.06 mg/g body wt) was not lowered. Myocardial vessel density was normalized, and sprouting from coronary rings increased by 50% in trained rats infused with ANG II compared with sedentary normotensive rats. Cardiac VEGF (Western blot analysis) was higher in hypertensive rats and not affected by exercise. Facing a similar increase in cardiac mass, intense training, but not ANG II hypertension, is accompanied by an increase in vascular density of the heart. The effect of training is unlikely related to changes in resting VEGF and may represent enhanced angiogenic capacity of the coronary vascular bed.
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PMID:Contrasting effect of exercise and angiotensin II hypertension on in vivo and in vitro cardiac angiogenesis in rats. 1876 71

Acute kidney injury induced by renal ischemia-reperfusion (I/R) compromises microvascular density and predisposes to chronic kidney disease (CKD) and sodium-dependent hypertension. VEGF-121 was administered to rats fed a standard (0.4%) sodium diet at various times following recovery from I/R injury for up to 35 days. VEGF-121 had no effect on the initial loss of renal function, as indicated by serum creatinine levels measured 24 h after injury. Serum creatinine levels declined thereafter, indicative of renal repair. Rats were then switched to an elevated (4.0%) sodium diet for an additional 28 days to induce CKD. The 4.0% sodium diet enhanced renal hypertrophy, interstitial volume, albuminuria, and cardiac hypertrophy relative to postischemic animals maintained on the 0.4% sodium diet. Administration of VEGF-121 from day 0 to 14, day 0 to 35, or day 3 to 35 after I/R suppressed the effects of sodium diet on CKD development, while delayed administration of VEGF-121 from day 21 to 35 had no effect. Endothelial nitric oxide synthase protein levels were upregulated in postischemic animals, and this effect was significantly increased by the 4.0% sodium diet but was not influenced by prior treatment with VEGF. Conversely, microvascular density was preserved in postischemic animals treated with VEGF-121 relative to vehicle-treated postischemic animals. These data suggest that early, but not delayed, treatment with VEGF-121 can preserve vascular structure after ischemia and influence chronic renal function in response to elevated sodium intake.
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PMID:VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury. 1879 50

Pre-eclampsia is a pregnancy-related condition characterized by hypertension, proteinuria and endothelial dysfunction. VEGF(165)b, formed by alternative splicing of VEGF (vascular endothelial growth factor) pre-mRNA, inhibits VEGF(165)-mediated vasodilation and angiogenesis, but has not been quantified in pregnancy. ELISAs were used to measure means+/-S.E.M. plasma VEGF(165)b, sEng (soluble endoglin) and sFlt-1 (soluble fms-like tyrosine kinase-1). At 12 weeks of gestation, the plasma VEGF(165)b concentration was significantly up-regulated in plasma from women who maintained normal blood pressure throughout their pregnancy (normotensive group, 4.90+/-1.6 ng/ml; P<0.01, as determined using a Mann-Whitney U test) compared with non-pregnant women (0.40+/-0.22 ng/ml). In contrast, in patients who later developed pre-eclampsia, VEGF(165)b levels were lower than in the normotensive group (0.467+/-0.209 ng/ml), but were no greater than non-pregnant women. At term, plasma VEGF(165)b concentrations were greater than normal in both pre-eclamptic (3.75+/-2.24 ng/ml) and normotensive (10.58 ng/ml+/-3.74 ng/ml; P>0.1 compared with pre-eclampsia) pregnancies. Patients with a lower than median plasma VEGF(165)b at 12 weeks had elevated sFlt-1 and sEng pre-delivery. Concentrations of sFlt-1 (1.20+/-0.07 and 1.27+/-0.18 ng/ml) and sEng (4.4+/-0.18 and 4.1+/-0.5 ng/ml) were similar at 12 weeks of gestation in the normotensive and pre-eclamptic groups respectively. Plasma VEGF(165)b levels were elevated in pregnancy, but this increase is delayed in women that subsequently develop pre-eclampsia. In conclusion, low VEGF(165)b may therefore be a clinically useful first trimester plasma marker for increased risk of pre-eclampsia.
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PMID:Failure to up-regulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia. 1907 60

The monoclonal antibody bevacizumab, targeted against the angiogenesis factor VEGF has clinical activity against several common cancers. In metastatic breast cancer it improves response rate and time to progression in combination with paclitaxel/docetaxel compared with paclitaxel/docetaxel alone; the drug is currently being investigated in other combination regimens and as adjuvant and neoadjuvant therapy in early breast cancer. It is generally well tolerated. Side effects, including hypertension, proteinuria, thrombosis and bleeding, are uncommon and usually managed easily. Based on the clinical efficacy of bevacizumab, other small-molecule oral antiangiogenesis agents are now also under development.
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PMID:Bevacizumab in the treatment of breast cancer. 1892 48


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