Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eicosanoids regulate various cellular functions that are important in physiological and pathophysiological processes. Arachidonic acid is released from membranes by phospholipase A(2) (PLA(2)) activity. Activated macrophages derived from mice lacking the 85-kDa group IV cytosolic PLA(2) (cPLA(2)) have a markedly reduced release of prostaglandin E(2) and leukotrienes B(4) and C(4). Under basal conditions and after furosemide, urinary prostaglandin E(2) excretion is reduced in cPLA(2)-knockout (cPLA(2)(-/-)) mice. Serum creatinine, Na(+), K(+), and Ca(2+) concentrations, glomerular filtration rate, and fractional excretion of Na(+) and K(+) are not different in cPLA(2)(-/-) and cPLA(2)(+/+) mice. Maximal urinary concentration is lower in 48-h water-deprived cPLA(2)(-/-) mice compared with cPLA(2)(+/+) animals (1,934 +/- 324 vs. 3,541 +/- 251 mmol/kgH(2)O). Plasma osmolality is higher (337 +/- 5 vs. 319 +/- 3 mmol/kgH(2)O) in cPLA(2)(-/-) mice that lose a greater percentage of their body weight (20 +/- 2 vs. 13 +/- 1%) compared with cPLA(2)(+/+) mice after water deprivation. Vasopressin does not correct the concentrating defect. There is progressive reduction in urinary osmolality with age in cPLA(2)(-/-) mice. Membrane-associated aquaporin-1 (AQP1) expression, identified by immunocytochemical techniques, is reduced markedly in proximal tubules of older cPLA(2)(-/-) animals but is normal in thin descending limbs. However, Western blot analysis of kidney cortical samples revealed an equivalent AQP1 signal intensity in cPLA(2)(+/+) and cPLA(2)(-/-) animals. Young cPLA(2)(-/-) mice have normal proximal tubule AQP1 staining. Collecting duct AQP2, -3, and -4 were normally expressed in the cPLA(2)(-/-) mice. Thus mice lacking cPLA(2) develop an age-related defect in renal concentration that may be related to abnormal trafficking and/or folding of AQP1 in the proximal tubule, implicating cPLA(2) in these processes.
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PMID:Renal concentrating defect in mice lacking group IV cytosolic phospholipase A(2). 1124 52

In 328 type 2 diabetic patients followed for 9.0 years (mean), we investigated whether endothelial dysfunction and chronic inflammation (estimated from plasma markers) can explain the association between (micro)albuminuria and mortality. Of the patients, 113 died. Mortality was increased in patients with baseline microalbuminuria or macroalbuminuria (odds ratios as compared with normoalbuminuria, 1.78 [P < 0.05] and 2.86 [P < 0.01]) and in patients with soluble vascular cell adhesion molecule 1 in the third tertile and C-reactive protein in the second and third tertiles (odds ratios as compared with the first tertile, 2.05 [ P < 0.01], and 1.80 [P < 0.05] and 2.92 [ P < 0.01]). These associations were mutually independent. The mean yearly change in urinary albumin excretion was 9.4%; in von Willebrand factor, 8.1%; in tissue-type plasminogen activator, 2.8%; in soluble vascular cell adhesion molecule 1, 5.2%; in soluble E-selectin, -2.3%; in C-reactive protein, 3.8%; and in fibrinogen, 2.3%. The longitudinal development of urinary albumin excretion was significantly and independently determined by baseline levels of and the longitudinal development of BMI, systolic blood pressure, serum creatinine, glycated hemoglobin and plasma von Willebrand factor (baseline only), soluble E-selectin (baseline only), tissue-type plasminogen activator, C-reactive protein, and fibrinogen. The longitudinal developments of markers of endothelial function and inflammation were interrelated. In type 2 diabetes, increased urinary albumin excretion, endothelial dysfunction, and chronic inflammation are interrelated processes that develop in parallel, progress with time, and are strongly and independently associated with risk of death.
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PMID:Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. 1191 39

Previous studies have shown that Japanese taxi drivers are exposed to more risk factors and have a higher mortality rate due to cardiovascular disease than other occupational groups. We investigated the effect of night taxi driving with a view to preventing acute events of cardiovascular disease among aged taxi drivers. Twenty-nine taxi drivers (41-67 years old) were examined for urine normetanephrine/creatinine, von Willebrand factor, anti-thrombin III, t-plasminogen activator-plasminogen activator inhibitor 1-complex, hematocrit, blood glucose and blood pressure in the morning and at midnight during a duty day and in the following morning. At the same time, the blood pressure and blood glucose of 46 taxi drivers (43-67 years old) in the morning after a night duty with little sleep and in the morning after daytime work and subsequent night sleep were compared. The results obtained indicate that the aggravation of sympathetic nervous system functions with disturbed circadian rhythms, increased blood coagulation and blood concentration, endothelial injury and the elevation of blood glucose at midnight or the next morning were induced by their night work. These conditions are supposed to favour acute vascular events in aged taxi drivers. Preventive measures considered include social support for anticoagulant food and water intake, short exercise and walking as well as taking a rest and a nap during night work.
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PMID:Searching for preventive measures of cardiovascular events in aged Japanese taxi drivers--the daily rhythm of cardiovascular risk factors during a night duty day. 1456 2

The majority of deaths among patients after renal transplantation is attributed to cardiovascular disease (CVD). Intima media thickness (IMT) of the common carotid artery is related to coronary and cerebrovascular arterial disease. One of the major causes of death due to CVD is acute coronary syndrome, which is precipitated by coronary plaque rupture and subsequent thrombosis. The aim of the study was to evaluate associations between some fibrinolytic factors: antigens of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), and thrombin-activatable fibrinolysis inhibitor (TAFI), and IMT in a population of renal transplant recipients. The study was performed on 33 Caucasian, clinically stable kidney transplant recipients (11 women, mean age 43 years, range 26 to 62 years). All the patients were on triple immunosuppressive regimen (cyclosporine, prednisone, and azathioprine) and had stable graft function (serum creatinine 1.7 +/- 0.7 mg/dL). The mean time since transplantation was 49.9 months (range 4.1 to 131.8 months). In univariate analysis IMT correlated significantly with age (r =.5; P =.001), pulse pressure (PP) (r =.4; P =.05), time on dialysis prior to transplantation (r =.6; P =.001), fibrinogen (r =.4; P =.02), and t-PA (r =.6; P =.001). Multiple regression analysis showed that t-PA antigen concentration (P =.001), fibrinogen (P <.05), and time on dialysis prior to transplantation (P <.05) were positive independent predictors of IMT. These data support the concept of the coincidence of disturbances in fibrinolysis and arterial remodelling in patients after kidney transplantation. On the other hand the study shows that the duration of dialysis therapy before transplantation is detrimental to the arterial vasculature.
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PMID:Plasma tissue-type plasminogen activator, fibrinogen, and time on dialysis prior to transplantation are related to carotid intima media thickness in renal transplant recipients. 1469 41

Endothelial dysfunction with atherosclerosis is a recognized complication of uremic patients. The hypoalbuminemia of peritoneal dialysis (PD) patients can induce a hypercoagulable and atherogenic state. In this study, we investigated the role played by malnutrition-inflammation syndrome on endothelial function markers in PD patients. We measured markers of nutrition [normalized protein catabolic rate (nPCR), albumin, prealbumin, insulin-like growth factor 1 (IGF-1), transferrin, and cholesterol], markers of endothelial damage and function [tissue-type plasminogen activator (tPA), thrombomodulin (TM), von Willebrand factor (vWF), and NO3 (representing NO)], markers of a coagulable state [fibrinogen and plasminogen activator inhibitor 1 (PAI-1)], markers of inflammation [tumor necrosis factor alpha (TNF alpha) and C-reactive protein (CRP)], and other endothelial injury factors [lipoprotein(a) [Lp(a)] and homocysteine]. We also performed an endothelial stimulation test consisting of right-arm venous occlusion (VO) for 10 minutes. The patients were divided into four groups according to their clinical atherosclerotic score (CAS). We studied 45 clinically stable PD patients. At baseline, statistically significant negative linear correlations were found between albumin and age (r = -0.54, p < 0.05), albumin and vWF post-VO (r = -0.54, p < 0.05), and albumin and TM (r = -0.36, p < 0.05), which are endothelial damage markers and prothrombotic factors. A positive linear correlation was seen between albumin and NO3 post-VO (r = 0.48, p < 0.05), indicating a high vasodilatation capacity. C-Reactive protein and TNF alpha showed a positive linear correlation (r = 0.5, p < 0.01). Similarly, TNF alpha showed a positive linear correlation with cardiovascular risk markers such as fibrinogen (r = 0.79, p < 0.01), PAI-1 (r = 0.44, p < 0.05), and homocysteine (r = 0.37, p < 0.05). Creatinine clearance showed a negative linear correlation with TM (r = -0.36, p < 0.05). Patients with albumin < 4 g/dL showed a lower tPA ratio, lower NO3, and a higher CRP, TNF alpha, and Lp(a) than did patients with albumin > 4 g/dL [tPA ratio: 2.1 +/- 1.56 (n = 29) vs. 2.6 +/- 2.3 (n = 16), p < 0.05; NO3: 47 +/- 27 micrograms/mL vs. 69 +/- 33 micrograms/mL, p < 0.05; CRP: 1.8 +/- 3 mg/dL vs. 1.1 +/- 1.6 mg/dL, p < 0.05; TNF alpha: 44.4 +/- 16 pg/mL vs. 36.6 +/- 21.4 pg/mL, p < 0.05; Lp(a): 55 +/- 39 mg/dL vs. 33 +/- 21 mg/dL, p < 0.05]. Patients with a worse CAS showed higher homocysteine levels and lower albumin values. Those relationships were maintained in both periods of the study. We found no relationships between dialysis dose and endothelial function markers. In conclusion, malnutrition-inflammation syndrome may contribute to endothelial dysfunction and, consequently, to prothrombotic and proatherogenic processes in PD patients.
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PMID:Malnutrition-inflammation syndrome is associated with endothelial dysfunction in peritoneal dialysis patients. 1476 71

Patients with renal impairment have an increased risk for cardiovascular disease, which may be the result of advanced glycation end products (AGEs). The aim of this study was to investigate the levels of AGE peptides in relation to kidney function and to study the relationship of AGE peptides with endothelial function and inflammation in type 1 diabetic patients. We measured plasma levels of AGE peptides with a simple fluorescent analytical procedure in patients with end-stage renal disease with or without diabetes and in 60 type 1 diabetic patients categorized as having normo-, micro-, or macroalbuminuria. Using enzyme-linked immunosorbent assays, we determined vascular cell adhesion molecule 1 (sVCAM-1), sE-selectin, plasminogen activator inhibitor 1 (PAI-1), tissue type-specific plasminogen activator (tPA), von Willebrand factor (vWF), and soluble thrombomodulin (sTM) to be markers of endothelial function and determined C-reactive protein (CRP) to be a marker of inflammation. AGE peptides were increased approximately fivefold in patients with end-stage renal disease, without difference between patients with or without diabetes. In type 1 diabetic patients, the increase of AGE peptides across the groups normo-, micro-, and macroalbuminuria (with medians [range] of 12.6% [7.8-27.2%], 12.1% [7.8-162%], and 46.5% [9.0-248.9%]) was associated with serum creatinine level and not with albumin excretion rate (AER). The relationship with serum creatinine decreased but remained significant after adjusting for age, sex, diabetes duration, hemoglobin A1c (HbA1c), AER, systolic and diastolic blood pressure (BP), and CRP in multiple linear-regression analysis. AGE peptide levels were significantly associated with sVCAM-1 and sTM, independently of serum creatinine. However, these relationships were no longer significant after adjusting for age, sex, diabetes duration, HbA1c, AER, systolic and diastolic BP, and CRP. This study shows that plasma levels of AGE peptides rise with renal impairment, as determined by serum creatinine. AGE peptides are associated with some markers of endothelial activation, which may suggest an involvement of AGE peptides in the acceleration of cardiovascular complications in type 1 diabetic patients with renal impairment.
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PMID:Plasma levels of AGE peptides in type 1 diabetic patients are associated with serum creatinine and not with albumin excretion rate: possible role of AGE peptide-associated endothelial dysfunction. 1603 90

Progression of renal disease and cardiovascular complications in type II diabetes mellitus have been shown to correlate with control of blood glucose, lipids, blood pressure, and smoking. These factors, however, do not appear to totally explain these diabetic complications. Renal disease and cardiovascular complications in type II diabetes are associated with vascular abnormalities and fibrosis, both of which may occur with impaired fibrinolysis. A cross-sectional study was therefore performed in 107 type II diabetic patients recruited from the Denver Metropolitan Area to examine the effect of impaired fibrinolysis, as assessed by the ratio of plasminogen activator inhibitor (PAI-1) to tissue-type plasminogen activator (t-PA). With urinary albumin excretion (UAE) as a risk factor for both renal disease progression and cardiovascular complications, the patients were analyzed with respect to UAE less than and greater than 1 gm/day. The age, blood glucose, hemoglobin A1C, duration of diabetes, lipids, body mass index, and smoking were no different between the groups. As expected, the group with greater UAE had worse renal function, the serum creatinine (1.98 +/- 0.24 vs 1.21 +/- 0.05 mg/dl, P < 0.001) and creatinine clearance (55.5 +/- 6.0 vs 76.8 +/- 2.7 ml/min, P < 0.001) were significantly different. The type II diabetic patients with greater UAE exhibited significantly higher PAI-1/t-PA (2.43 +/- 0.26 vs 1.85 +/- 0.07, P < 0.03). The past history of cardiac complications was also higher (87.5 vs 72.3%, P < 0.07) in the diabetic patients with more impaired fibrinolysis and greater UAE. Thus a prospective, randomized clinical trial in type II diabetes with PAI-1 inhibitors is needed.
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PMID:Impaired fibrinolytic activity in type II diabetes: correlation with urinary albumin excretion and progression of renal disease. 1659 98

Microalbuminuria (MA) is known as a marker for generalized vascular dysfunction. It occurs most commonly in the setting of diabetes and hypertension; however, its association with cerebral small vessel disease (SVD) in community-based elderly remains to be clarified. In this cross-sectional analysis, we evaluated the association between MA and cerebral SVD in total 651 community-based elderly subjects. We assessed cardiovascular risk factors by interviews and physical examinations, including an evaluation of urinary albumin creatinine ratio (UACR). All subjects underwent brain magnetic resonance imaging (MRI) and carotid ultrasonography. As endothelial markers, the serum levels of thrombomodulin (TM) and a tissue-type plasminogen activator/ plasminogen activator inhibitor-1 complex were also studied. The mean TM and UACR were higher in subjects with lacunar infarcts or with moderate white matter hyperintensities (mWMH) on MRI than in those without them. Additionally, the prevalence of lacunar infarcts or mWMH was higher in the highest tertile of UACR level than in the lowest or middle tertile. Furthermore, in logistic regression analysis, the elevation of logarithmically transformed UACR (log UACR) was associated with the higher likelihood for total lacunar infarcts (odds ratio [OR], 1.85 per one log UACR increase), multiple lacunar infarcts (OR, 1.89 per one log UACR increase), and mWMH (OR, 2.15 per one log UACR increase). The present study revealed that levels of urinary albumin are associated with cerebral SVD, independently of traditional cerebrovascular risk factors, in community-based elderly.
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PMID:Microalbuminuria is a risk factor for cerebral small vessel disease in community-based elderly subjects. 1732 Sep 8

Thrombolytic agents activate plasminogen and induce a systemic fibrinolytic and anticoagulant state. Two thrombolytic drugs are used frequently in practice: streptokinase (SK) and alteplase (t-PA). Streptokinase mainly undergoes renal elimination with a half-life of 11-17 min, while alteplase is eliminating by the liver with a half-life of 4-6 min. Our goal was to examine whether renal and hepatic function influence the elimination and metabolism of thrombolytics and the efficacy of percutaneous coronary intervention (PCI) after using alteplase or streptokinase. 416 patients with myocardial infarction (MI) were treated from January 2001 to December 2003 (228 male and 189 female). Alteplase was used in 9 men and 6 women (mean age: 53.88 +/- 9.61 vs. 65.33 +/- 9.87 years, p = 0.07). Patients who underwent rescue PCI after administration of alteplase had slightly higher hepatic enzyme levels/alanine transaminase (ALT): 47.85 vs. 41.4 U/l; gamma-glutamyl transpeptidase (GGT): 69.5 vs. 44.8 U/l/. All patients treated with alteplase survived, rescue PCI was done in 8 cases. Streptokinase was used in 36 men and 28 women (mean age: 63.33 +/- 10.51 vs. 63 +/- 12.03 years, p = 0.9). We did not find a difference between serum creatinine levels of patients who received streptokinase and underwent PCI as compared to those who had not. Rescue PCI was done in 16 cases. 12 patients died in this group. In conclusion we have not found a significant correlation between the use of the thrombolytics and hepatic or renal function; this could indicate that such a slight impairment of liver and renal function does not influence pharmacokinetic properties of thrombolytics.
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PMID:Does impairment of renal and hepatic function influence the metabolism of thrombolytics in patients with myocardial infarction? 1844 16

There are some doubts whether in a severe renal failure the dose of alteplase should not be modified, especially when its plasma clearance may be decreased by liver ischemia. The authors present a case of a 67-year old woman with massive pulmonary embolism (PE) and acute renal failure (creatinine 580 micromol/l) of a mixed etiology (renal calculosis with hydronephrosis and shock as PE presentation). Alteplase administration (10 mg bolus followed by reduced to 50 mg two hours infusion) resulted in hemodynamic stabilization but was complicated by gross subcutaneous hematomas, intensive epistaxis and hematuria, and hemoglobin decrease which required blood transfusions.
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PMID:[Massive pulmonary embolism treated with a reduced dose of alteplase in a patient with acute renal failure]. 1880 42


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