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)

The urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a lysosomal enzyme of the renal tubular cells was analyzed in 177 women divided into nonpregnant healthy controls (n = 46), normal pregnant women in their third trimester (n = 49), pregnant women with transient hypertension (n = 43), and women with preeclampsia (n = 39). Urinary activity of NAG was increased in normal pregnant women and in patients with transient hypertension in pregnancy compared to nonpregnant healthy controls. In preeclamptic women, this increase was found to be much higher than that corresponding to their gestational age; this fact is due to the tissue ischemia that precedes glomerular endotheliosis, but also tubular lesions caused by arteriolar vasoconstriction may have an important role.
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PMID:Urinary N-acetyl-beta-glucosaminidase in the prediction of preeclampsia. 977 20

Pre-eclampsia is a severe form of hypertension induced by pregnancy. In pre-eclampsia, there is deficient trophoblast invasion of the spiral arteries terminating in the placental bed. Perhaps some abnormality occurs in the immunosuppressive process as the maternal immune system encounters paternal antigens expressed by immunosuppressive decidual cells. This immunosuppressive abnormality might cause the deficient trophoblast invasion. Abnormal placentation might then lead to maternal endothelial cell damage by an ongoing process. There might be a recurring sequence of 4 steps: (1) The placenta releases trophoblastic cells with potentially cytotoxic characteristics. These circulating trophoblastic cells have an abnormal pattern of expression of integrins and perhaps other glycoproteins or proteins. (2) The circulating trophoblastic cells loosely bind to maternal endothelial cells, targeting them for anti-tumourigenesis. (3) The maternal immune system reacts against targeted maternal endothelial cells through anti-tumourigenic mechanisms. (4) Widespread maternal endothelial damage causes the characteristic kidney lesion called glomerula endotheliosis.
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PMID:Pre-eclampsia: a mistake of trophoblastic cells for tumour cells? 1053 5

Complement (C) 4d and cofactor C4b binding protein (C4bp) are detected in the glomerular capillary walls of a patient with preeclampsia. A 32-year-old nullipara had proteinuria of 1.2 g/d and edema at the 33rd week of pregnancy. Gradually the urinary protein excretion increased, reaching 5.1 g/d at the 37th week. The patient also showed hypertension at this stage. After normal mature delivery, the level of the urinary protein excretion remained at 3 to 4 g/d. Renal biopsy performed by means of light and electron microscopy, 15 days after delivery, showed almost normal glomeruli and modest subendothelial widening. Immunohistochemistry indicated that immunoglobulin (Ig) A, IgG, C1q, C3c, and C4c were not deposited in the glomeruli, whereas weakly positive IgM and fibrin-related antigen (FRA) were observed. Conversely, C4d, C3d, and C4bp were strongly deposited. Protein S (PS) also was observed, with a similar distribution pattern to that of C4bp. Immunoelectron microscopy showed the deposition of C4d along the capillary walls and of C4bp in the subendothelium. These findings suggest that the C4 activation process as well as the regulation process of C system and of the inflammatory coagulation axis by C4bp and PS may play an important role in the pathophysiology of preeclampsia, so-called glomerular capillary endotheliosis (GCE).
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PMID:C4d and C4bp deposition along the glomerular capillary walls in a patient with preeclampsia. 1113 95

p57Kip2, a potent inhibitor of several cyclin/cyclin dependent kinase complexes (CDK ), is a paternally imprinted gene in both humans and mice, and here we show that pregnant mice which are heterozygous for p57Kip2 deficiency display symptoms similar to preeclampsia. p57-/+ (heterozygotes for p57Kip2 ) female mice that were mated with p57-/+ males showed hypertension, proteinuria, thrombocytopenia, decreased anti-thrombin III activity, and increased endothelin levels during late pregnancy. In their kidneys, endotheliosis of glomeruli were recognized along with fibrinoid or hyalinoid deposits. These characteristics were also observed in pregnant p57-/+ females that were mated with wild type males, but not in pregnant wild type females mated with p57-/+ males or wild type males. The pregnant p57-/+ mice had conceptuses both with and without p57Kip2 expression. The conceptuses without p57Kip2 expression showed trophoblastic hyperplasia, which mimics the hallmark proliferation of intermediate trophoblasts in clinical preeclampsia. It is suggested that the preeclampsia-like symptoms of the pregnant p57-/+ mice might have been induced by the conceptus(es) without p57Kip2 expression. In addition, pregnant p57-/+ mice might serve as a new animal model for preeclampsia characterized by trophoblastic hyperplasia.
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PMID:Deficiency in p57Kip2 expression induces preeclampsia-like symptoms in mice. 1246 47

Preeclampsia, a syndrome affecting 5% of pregnancies, causes substantial maternal and fetal morbidity and mortality. The pathophysiology of preeclampsia remains largely unknown. It has been hypothesized that placental ischemia is an early event, leading to placental production of a soluble factor or factors that cause maternal endothelial dysfunction, resulting in the clinical findings of hypertension, proteinuria, and edema. Here, we confirm that placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of VEGF and placental growth factor (PlGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt1 that fall after delivery. We demonstrate that increased circulating sFlt1 in patients with preeclampsia is associated with decreased circulating levels of free VEGF and PlGF, resulting in endothelial dysfunction in vitro that can be rescued by exogenous VEGF and PlGF. Additionally, VEGF and PlGF cause microvascular relaxation of rat renal arterioles in vitro that is blocked by sFlt1. Finally, administration of sFlt1 to pregnant rats induces hypertension, proteinuria, and glomerular endotheliosis, the classic lesion of preeclampsia. These observations suggest that excess circulating sFlt1 contributes to the pathogenesis of preeclampsia.
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PMID:Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. 1261 13

Glomerular capillary endotheliosis is a lesion of endothelial cell injury. Morphological characteristics are endothelial swelling with glomerular hypertrophy and a reduction in capillary lumen size. This lesion commonly is found in patients with thrombotic microangiopathy, but similar histopathologic characteristics have been reported in patients with other diseases. A previously healthy 39-year-old woman presented with progressive lower-extremity swelling and arthralgias for 1 week. She had no other symptoms and denied prior illness. Her examination was remarkable for hypertension and pitting edema. Urine showed dysmorphic red blood cells and proteinuria. Serum creatinine level increased from 1.1 to 2.0 mg/dL (97 to 177 micromol/L) during several weeks. She did not meet criteria for systemic lupus erythematosus. Other test results included a negative pregnancy test and normal complement levels. Additional workup was negative for other causes of glomerular capillary endotheliosis. She underwent 2 renal biopsies. The first showed marked endothelial cell swelling, and the second biopsy 2 months later showed disease progression. Both were consistent with glomerular capillary endotheliosis. Proteinuria and serum creatinine level elevation responded to methylprednisolone therapy within 1 week, recurred after steroid doses were tapered, and responded again after restarting steroid therapy with monthly cyclophosphamide infusions. The differential diagnosis for glomerular capillary endotheliosis is limited. Various causes have been implicated, such as dysregulation of vascular endothelial growth factor, abnormal collagen production, and endothelial abnormalities. We did not identify prior cases of idiopathic glomerular capillary endotheliosis in the literature. Idiopathic glomerular capillary endotheliosis may be a newly recognized entity potentially responsive to steroid and cytotoxic regimens.
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PMID:Steroid-responsive idiopathic glomerular capillary endotheliosis: case report and literature review. 1595 39

A 35-year-old Japanese woman for whom a previous health checkup showed normal blood pressure and urinalysis results without serological abnormalities developed nephrotic syndrome with severe hypertension at 15 gestational weeks. The renal biopsy performed at 17 weeks of gestation showed severe glomerular capillary endotheliosis. By means of electron microscopy, no electron-dense deposits were observed in glomeruli, and foot-process arrangement was normal. Histological findings indicated the patient's glomerular damage was caused by the mechanisms of preeclampsia. The patient underwent an elective abortion at 18 weeks of gestation. Clinical abnormalities vanished completely within 3 months after the elective abortion, which provided additional evidence that proteinuria and hypertension were caused purely by pregnancy. In general, the term preeclampsia refers to new onset of hypertension and proteinuria after 20 weeks of gestation. When proteinuria or hypertension is newly observed before 20 weeks of gestation, they are practically associated with triploidy, trophoblastic disease, or antiphospholipid syndrome. However, our case was not associated with them. Therefore, we called this case "pure" preeclampsia. We confirm the notion for the first time that preeclampsia associated with glomerular capillary endotheliosis can occur before 20 weeks of gestation. In addition, this report describes the earliest onset of preeclampsia compared with previously published reports. We also discuss causes of preeclampsia in early gestation and refer to the issue of the application of renal biopsies during pregnancy.
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PMID:A case of "pure" preeclampsia with nephrotic syndrome before 15 weeks of gestation in a patient whose renal biopsy showed glomerular capillary endotheliosis. 1693 Dec 25

Glomerular filtration rate and renal plasma flow increase by 40 to 65 and 50 to 85%, respectively, during normal pregnancy in women. Studies using the gravid rat as a model have greatly enhanced our understanding of mechanisms underlying these remarkable changes in the renal circulation during gestation. Hyperfiltration is largely due to increased renal plasma flow, the latter attributable to profound reductions in both the renal afferent and efferent arteriolar resistances. The ovarian hormone, relaxin, mediates renal vasodilation during pregnancy. Relaxin increases vascular gelatinase activity, thereby converting big ET to ET(1-32), which leads to renal vasodilation, hyperfiltration and reduced myogenic reactivity of small renal arteries via the endothelial ET(B) receptor and nitric oxide. Serum concentration of uric acid falls during normal pregnancy as a consequence of increased GFR and/or reduced proximal tubular reabsorption. The elevated urinary excretion of protein during pregnancy is secondary to increased GFR, reduced proximal tubular reabsorption, and perhaps alteration in the electrostatic charge of the glomerular filter. Whether the tubular secretion of Tamm-Horsfall protein increases during normal pregnancy is uncertain. In most women with preeclampsia, renal plasma flow and glomerular filtration rate are at most only modestly decreased as a consequence of increased afferent arteriolar resistance and/or reduced ultrafiltration coefficient. Serum uric acid concentrations are increased mainly as a consequence of reduced renal clearance. Reduced GFR leads to decreased filtered load of uric acid, and plasma volume contraction contributes to increased proximal tubular reabsorption coupled to sodium. The increase in urinary protein excretion in preeclampsia occurs secondary to alterations in the size and/or charge selectivity of the glomerular filter, possible increases in glomerular capillary pressure, and compromise of proximal tubular reabsorption. The renal histologic lesion characteristic of preeclampsia is termed "glomerular endotheliosis". Recent evidence suggests that anti-angiogenic factors emanating from the placenta in preeclampsia contribute to glomerular endotheliosis, proteinuria, and hypertension during disease.
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PMID:Renal function during normal pregnancy and preeclampsia. 1712 52

Preeclampsia affects 3-5% of pregnancies and can have a significant impact on health for both mother and fetus. Risk factors include maternal co-morbidities such as obesity and chronic hypertension, paternal factors, and genetic factors. New hypertension and proteinuria during the second half of pregnancy are key diagnostic criteria, but the clinical features and associated prognostic implications are somewhat heterogeneous and may reflect different mechanisms of disease. Renal dysfunction and proteinuria correspond to the pathologic finding of glomerular endotheliosis, and generally resolve after cure of preeclampsia through fetal and placenta delivery. The molecular mechanisms behind this disease are being discovered and refined. The initial etiologic agents are currently unknown. Pathologic studies show abnormal development of an ischemic placenta with a high-resistance vasculature, which cannot deliver an adequate blood supply to the fetoplacental unit. Endothelial dysfunction plays a central role in the pathogenesis of the maternal syndrome. Dysfunctional endothelial cells produce altered quantities of vasoactive mediators, which lead to a tip in the balance towards vasoconstriction. An imbalance in circulating angiogenic factors is emerging as a prominent mechanism that mediates the endothelial dysfunction and the clinical signs and symptoms of preeclampsia. Soluble fms-like tyrosine kinase 1 (sFlt1), an endogenous anti-angiogenic factor that is a potent vascular endothelial growth factor (VEGF) antagonist, is highly elevated in preeclampsia. VEGF is not only important in angiogenesis, but also in maintaining endothelial health including the formation of endothelial fenestrae (a hallmark of the glomerular vascular endothelium). sFlt1 overexpression in animals induces glomerular endotheliosis with the loss of endothelial fenestrae that resembles the renal histological lesions of preeclampsia. More severe forms of preeclampsia, including the HELLP syndrome, may be explained by a concomitant elevation in both sFlt1 and soluble endoglin, another anti-angiogenic factor. Unraveling of the molecular mechanisms behind preeclampsia may help to expand our armamentarium to treat patients in a more directed fashion, as current management consists of supportive care and expedited delivery. Finally, long-term outcomes of women with preeclampsia include a significantly increased risk for hypertension and cardiovascular disease, including mortality, which may warrant more aggressive screening and treatment in this population.
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PMID:Pre-eclampsia: clinical manifestations and molecular mechanisms. 1757 Sep 33

Preeclampsia is a pregnancy-specific disorder that complicates approximately 5% of all pregnancies, making it perhaps the most common glomerular disease in the world. It is characterized by new-onset hypertension and proteinuria, in association with a characteristic glomerular lesion, endotheliosis. "Glomerular endotheliosis" represents a specific variant of thrombotic microangiopathy that is characterized by glomerular endothelial swelling with loss of endothelial fenestrae and occlusion of the capillary lumens. Associated thrombosis is unusual. Recent evidence suggests that this unusual glomerular lesion is mediated by a soluble vascular endothelial growth factor receptor that deprives glomerular endothelial cells of the vascular endothelial growth factor that they require, leading to cellular injury and disruption of the filtration apparatus with subsequent proteinuria. This review summarizes the histologic changes and the pathogenesis of the glomerular lesions of preeclampsia.
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PMID:The glomerular injury of preeclampsia. 1763 33


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