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)

Over many decades, several attempts have been made to treat hypertension using a vaccination strategy to inhibit the renin-angiotensin system. Renin vaccination successfully inhibited renin activity and reduced blood pressure in animal models, but caused autoimmune disease of the kidney. By contrast, most previous studies of angiotensin vaccination failed to reduce blood pressure in animal models, despite producing high titers of antibodies that prevented the pressor response to exogenous angiotensins. Angiotensin vaccination is being revisited as a strategy for treating hypertension, in the hope that new conjugates of angiotensin I and angiotensin II will produce antibodies of sufficient titer and affinity to reduce blood pressure in patients with hypertension. A recent clinical study of angiotensin II vaccination provided some cause for optimism, but many hurdles remain before this strategy can compete with current oral medications for hypertension.
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PMID:Angiotensin vaccination: what is the prospect of success? 1914 3

Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we generated MRL-Faslpr/lpr (lpr) mice lacking the major murine type 1 angiotensin receptor (AT1A); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, AT1A deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of AT1A-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by AT1A deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, AT1B, and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of AT1A-deficient lpr mice, and they showed evidence of exaggerated AT1B receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since AT1A-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension.
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PMID:Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis. 1928 96

High levels of CRP relate with advanced disease and poor prognosis of cancer patients. CRP serum levels were measured in 684 cancer patients who had undergone complete surgery or inoperable patients. Patients with inoperable tumors had significantly higher CRP levels (1.21 +/- 2.2 vs. 0.40 +/- 0.4 mg/dL; p < 0.0001). No association with gender, diabetes, autoimmune disease, thyroid disease or allergy was noted. Significantly higher CRP levels were noted in operated patients with hypertension (0.55 +/- 0.5 vs. 0.35 +/- 0.4; p = 0.001), coronary disease (0.73 +/- 0.8 vs. 0.39 +/- 0.4; p = 0.01) and obesity (0.51 +/- 0.5 vs. 0.37 +/- 0.4; p = 0.04). On the contrary, analysis in the group of inoperable patients showed that hypertensive patients had significantly lower CRP levels (0.64 +/- 1.0 vs. 1.36 +/- 2.4; p = 0.008). Although the tumor itself is the main factor defining increased CRP levels in cancer patients, hypertension, coronary disease and obesity are also linked with high CRP levels. Anti-hypertensive drugs appear as potent suppressors of the tumor-induced CRP production.
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PMID:Serum C-reactive protein (CRP) levels in cancer patients are linked with tumor burden and are reduced by anti-hypertensive medication. 1937 47

Antiphospholipid antibodies are a heterogeneous group of autoantibodies associated with the hypercoagulable state affecting all vascular districts with thrombosis named antiphospholipid syndrome (APS). APS is an autoimmune disease with multifactorial etiology that includes cellular, molecular, genetic and pathogenic mechanisms. The APS clinical features are a combination of arterial and/or venous thrombosis, hematological events, recurrent fetal losses, neurological disorders and intra-abdominal manifestations. The renal involvement is associated with both primary and secondary APS. Clinical features include hypertension, renal artery stenosis, thrombotic microangiopathy and other histological manifestations of the nephropathy (APSN), venous renal thrombosis, APSN in the course of systemic lupus erythematosus and renal failure. APSN is an independent risk factor that should be included in the classification criteria for definite APS with characteristic clinical and histological features.
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PMID:Antiphospholipid antibodies and renal involvement. 1971 97

Excessive production of aldosterone leads to the development of hypertension and cardiovascular disease by generating an inflammatory state that can be promoted by T cell immunity. Because nature and intensity of T cell responses is controlled by dendritic cells (DCs), it is important to evaluate whether the function of these cells can be modulated by aldosterone. In this study we show that aldosterone augmented the activation of CD8(+) T cells in a DC-dependent fashion. Consistently, the mineralocorticoid receptor was expressed by DCs, which showed activation of MAPK pathway and secreted IL-6 and TGF-beta in response to aldosterone. In addition, DCs stimulated with aldosterone impose a Th17 phenotype to CD4(+) T cells, which have recently been associated with the promotion of inflammatory and autoimmune diseases. Accordingly, we observed that aldosterone enhances the progression of experimental autoimmune encephalomyelitis, an autoimmune disease promoted by Th17 cells. In addition, blockade of the mineralocorticoid receptor prevented all aldosterone effects on DCs and attenuated experimental autoimmune encephalomyelitis development in aldosterone-treated mice. Our data suggest that modulation of DC function by aldosterone enhances CD8(+) T cell activation and promotes Th17-polarized immune responses, which might contribute to the inflammatory damage leading to hypertension and cardiovascular disease.
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PMID:Aldosterone promotes autoimmune damage by enhancing Th17-mediated immunity. 1994 98

Maternal floor infarction (MFI) is an unusual, idiopathic placental disorder characterized by deposition of amorphous fibrinoid material along the maternal aspect of the intervillous space. This condition is associated with poor perinatal outcome-in particular, spontaneous abortion-fetal growth restriction, and stillbirth, with a high recurrence rate in subsequent pregnancies. It is unknown whether MFI is a single entity or the common end point of different insults. Most studies have linked MFI to underlying maternal disorders including gestational hypertension, autoimmune disease, and thrombophilia. In contrast, there have been only a few case reports regarding the possibility of a fetal basis for MFI. We report 2 cases of MFI in fetuses who suffered from oligohydramnios as a result of bilateral cystic renal dysplasia. These 2 cases suggest the concept that fetoplacental factors may also play a role in MFI. It is speculated that the mechanism might involve changes in intrauterine hydrostatic pressure gradients.
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PMID:Maternal floor infarction associated with oligohydramnios and cystic renal dysplasia: report of 2 cases. 2001 40

Systemic sclerosis (SSc) is an autoimmune disease of unknown origin. The clinical hallmarks are progressive fibrosis of skin and internal organs and vasculopathic changes in the form of digital ulcers and pulmonary arterial hypertension. The chronicity and heterogeneity of the disease has hampered research in SSc in the past, but new research tools and animal models have contributed to a greater understanding of the pathogenesis of SSc and resulted in new findings in the fields of genomics, cytokine expression, autoantibodies and abnormalities of blood progenitor or effector cells. As a consequence, targeted therapeutic compounds such as imatinib are currently under clinical investigation. Whilst the search for an effective "targeted therapy" is still ongoing, autologous stem cell transplantation represents a "multitarget" approach aiming at "resetting" the immune system. This review gives an overview of the translation from pathogenic findings into therapeutical application.
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PMID:New pathogenic and therapeutic concepts in systemic sclerosis. 2010 46

Systemic sclerosis (SSc) is an autoimmune disorder with clinical manifestations resulting from immune activation, fibrosis development and damage of small blood vessels. Although there have been no established treatments for SSc, lots of new treatments targeting organ and pathogenesis are in the process of development. Transforming growth factor (TGF)-beta is a major cytokine involved in the pathogenesis of fibrosis in SSc. The blockade of cell surface molecules capable of activating latent TGF-beta, blockade of ligand by the pan-isoform-specific antibody, soluble TGF-beta receptors and a recombinant latency associated peptide, as well as inhibitors for ALK5 and Smad3 are the potential strategies to abolish the pathological activation of TGF-beta signaling in SSc fibroblasts. Besides TGF-beta, connective tissue growth factor (CTGF)/CCN2, platelet-derived growth factor (PDGF) and endothelin-1 are the candidates for the new therapeutic targets. As for immune dysfunction in SSc, i.v. immunoglobulin infusion, stem cell transplantation and B-cell depletion are potential new therapies under or awaiting a randomized, double-blind, placebo-controlled trial, although their efficacies are still controversial. Phosphodiesterase-5 inhibitors, endothelin receptor antagonists and inhibitors for serotonin signaling are the new therapeutic targets for Raynaud's phenomenon, digital ulceration and pulmonary arterial hypertension in SSc. Imatinib mesylate may be a novel new therapy for fibrosis and vasculopathy in SSc because it reverses the expression levels of Fli1, which is a transcription factor downregulated in SSc through an epigenetic mechanism and is likely to be involved in the development of fibrosis and vasculopathy in this disease. Potential therapeutic targets other than those described above are also reviewed.
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PMID:Future treatments in systemic sclerosis. 2017 40

The PROLONG randomised clinical trial showed that an abnormal D-dimer at one month after vitamin K antagonist (VKA) suspension for a first episode of unprovoked venous thromboembolism (VTE) is associated with a higher risk of recurrence. However, other patient characteristics, such as comorbidities, in combination with D-dimer could also influence the recurrence risk. It was the objective of this study to assess the predictive value of comorbidities and D-dimer in combination for recurrence after withdrawal of VKA in patients enrolled in the PROLONG study. On the day of VKA suspension, the presence of known (coronary, peripheral,cerebral) vascular disease, chronic inflammatory bowel disease, chronic obstructive pulmonary disease, autoimmune disease, diabetes, arterial hypertension, obesity and dyslipidaemias was registered. D-dimer was measured at 30 +/- 10 days afterwards. The primary outcome was recurrent objectively documented VTE. Mean follow-up was 2.55 years. An abnormal D-dimer was observed in 44% (135/309) of patients with comorbidities and in 29% (87/299) of patients without (p=0.0003). An on-treatment analysis was conducted in 483 patients in whom VKAs were not resumed. In patients with a normal D-dimer, recurrences were observed in 14.3% (24/168) of patients with comorbidities and 10.8% (22/203) of subjects without (p=ns). In patients with an abnormal D-dimer, recurrences were observed in 24.6% (16/65) patients with comorbidities and 21.3% (10/47) of patients without (p=ns). Although abnormal D-dimer levels were significantly more frequent in patients with comorbidities, D-dimer was an independent risk factor for recurrence and the presence of comorbidities did not increase the risk of recurrence associated with an abnormal post-anticoagulation D-dimer.
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PMID:Comorbidities, alone and in combination with D-dimer, as risk factors for recurrence after a first episode of unprovoked venous thromboembolism in the extended follow-up of the PROLONG study. 2035 67

Systemic lupus erythematosus (SLE) is a chronic, relapsing and remitting autoimmune disease of unknown etiology. As in other rheumatic diseases sicca syndrome is often present. Additionally retinal vascular pathologies such as cotton wool spots and intraretinal hemorrhages are present in 7-8% of patients with SLE. SLE-related retinal vascular pathologies are activity markers and a prognostic factor for poor outcome. The case of a 38-year-old patient is reported with decompensated SLE who presented in our clinic with floaters and flickering scotoma but good visual acuity. Funduscopy and fluorescence angiography revealed bilateral choroidal vessel occlusions. Additionally, a hemorrhagic choroidal infarction and a preretinal hemorrhage were detected in the right eye. In summary SLE can result in choroidal vasoocclusion especially if decompensated arterial hypertension is present.
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PMID:[Choroidal vascular occlusion]. 2053 75


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