Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protection against ischemic kidney injury is afforded by 24 h of ureteral obstruction (UO) applied 6 or 8 days prior to the ischemia. Uremia or humoral factors are not responsible for the protection, since unilateral UO confers protection on that kidney but not the contralateral kidney. Prior UO results in reduced postischemic outer medullary congestion and leukocyte infiltration. Prior UO results in reduced postischemic phosphorylation of c-Jun N-terminal stress-activated protein kinase 1/2 (JNK1/2), p38, mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and MKK3/6. Very few cells stain positively for proliferating cell nuclear antigen after obstruction, indicating that subsequent protection against ischemia is not related to proliferation with increased numbers of newly formed daughter cells more resistant to injury. UO increases the expression of heat shock protein (HSP)-25 and HSP-72. The increased HSP-25 expression persists for 6 or 8 days, whereas HSP-72 does not. HSP-25 expression is increased in the proximal tubule cells in the outer stripe of the outer medulla postobstruction, prior to, and 24 h after ischemia. In LLC-PK(1) renal epithelial cells, adenovirus-expressed human HSP-27 confers resistance to chemical anoxia and oxidative stress. Increased HSP-27 expression in LLC-PK(1) cells results in reduced H(2)O(2)-induced phosphorylation of JNK1/2 and p38. In conclusion, prior transient UO renders the kidney resistant to ischemia. This resistance to functional consequences of ischemia is associated with reduced postischemic activation of JNK, p38 MAP kinases, and their upstream MAPK kinases. The persistent increase in HSP-25 that occurs as a result of UO may contribute to the reduction in phosphorylation of MAPKs that have been implicated in adhesion molecule up-regulation and cell death.
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PMID:Prevention of kidney ischemia/reperfusion-induced functional injury, MAPK and MAPK kinase activation, and inflammation by remote transient ureteral obstruction. 1169 40

Peripheral arterial occlusive disease (PAOD) accounts for significant morbidity and mortality among end-stage renal disease (ESRD) patients but has not been as extensively studied as other kinds of atherosclerotic disease in this population. The current epidemiology and management of PAOD in ESRD patients is here reviewed and target areas for future research are identified. The prevalence of PAOD appears to be much higher among ESRD patients than in the general population. Risk factors for disease among ESRD patients are not well understood but probably include both conventional and dialysis or uremia-associated risk factors. Standard diagnostic techniques used to identify PAOD in the general population may not be as helpful in ESRD patients because many of these tests are inaccurate in the settings of vascular calcification and small-vessel disease. Despite the fact that this is a common disease in ESRD patients, most of these patients are not screened for PAOD. Interventions that have proven effective in the prevention and treatment of PAOD in the general population, such as smoking cessation, preventive foot care, and exercise, have not been systematically applied to ESRD patients. Furthermore, the optimal management of ischemic ulceration and gangrene in ESRD patients is quite controversial, and better algorithms for the prevention and management of PAOD in ESRD patients are needed. In conclusion, PAOD is common in ESRD patients. Future research should identify risk factors for disease in this population, and efforts should be made to develop strategies for the effective prevention and management of limb ischemia in this population.
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PMID:Lower-extremity peripheral arterial disease among patients with end-stage renal disease. 1172 55

Cardial death caused by ischemia, which is not necessarily connected with coronary arterial changes, represents the main death cause in chronic renal failure patients. The present overview article compiles the latest findings on structural and functional changes of the heart and vessels in uremia, which have a potential effect on the ischemia tolerance of the myocardium and thus help to explain the high cardiovascular mortality in chronic renal failure. The cardiovascular structural changes comprise: 1. A left ventricular myocardium hypertrophy, 2. an interstitial myocardium fibrosis and 3. changes in the myocardial microcirculation like, above all, a rarefaction of the intramyocardial capillaries with increase in the intercapillary oxygen diffusion passage and a vascular wall thickening of intramyocardial arteries. In addition, characteristic metabolic changes, like for instance a decrease of phosphates rich in energy, which contribute likewise to a heightened ischemia sensitivity of the myocardium. At the same time an involvement of extra-myocardial vascular changes is also probable in the development of the prognostically unfavorable myocardium hypertrophy in chronic renal failure. These extracardial vascular changes consist, above all, of a wall thickening of the aorta, of the peripheral arteries and veins with reduction of the share of elastic fiber, of an increase in the extracellular matrix and of a diffuse media calcification and lead to an increase in vascular stiffness and to reduction of aortal compliance.
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PMID:Cardiovascular changes in chronic renal failure--pathogenesis and therapy. 1222 29

The influence of chronic renal failure on renal susceptibility to an acute ischemic insult was evaluated. Recipient Lewis rats were randomly assigned to undergo 5/6 nephrectomy (chronic renal failure, CRF) or sham operation (normal renal function, NRF). After 11 weeks, normal kidneys of Lewis donor rats were transplanted in the recipients. The outcome of the isografts was assessed. Filtration capacity of the isografts in the CRF rats was preserved to approximately one-quarter of its normal capacity on the 1st day post-transplantation, whereas it fell to 0 in the NRF rats. This was reflected by a significantly higher increase in serum creatinine in the latter group. The isografts in the CRF rats had a significantly lower degree of acute tubular necrosis and no increase in the number of macrophages and T lymphocytes in the first 24 h in contrast to the NRF rats. Epithelial regeneration and repair started earlier in the CRF group. In conclusion, the present study indicated that CRF blunted ischemia/reperfusion injury of a transplanted kidney, and that its regeneration capacity was certainly not hampered by the presence of chronic uremia. These results will be the basis for studies on modulation of early leukocyte-endothelial interactions resulting from immunological disturbances inherent to the uremic environment.
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PMID:Acute ischemia/reperfusion injury after isogeneic kidney transplantation is mitigated in a rat model of chronic renal failure. 1275 13

In patients with renal failure, myocardial infarction (MI) is more frequent and the rate of death from acute MI is very high. It has been argued that ischemia tolerance of the heart is reduced in uremia, but direct evidence for this hypothesis has not been provided. It was the purpose of this study (1) to ligate the left coronary artery and to measure the nonperfused area (risk area: total infarction plus penumbra) as well as the area of total infarction in subtotally nephrectomized (SNX) rats compared with sham-operated pair-fed control rats and (2) to examine the effects of potential confounders such as BP, sympathetic overactivity, and salt retention. The left coronary artery was ligated for 60 min, followed by reperfusion for 90 min. For visualizing perfused myocardium, lissamine green ink was injected. The nonperfused area (lissamine exclusion) and the area of total infarction (triphenyltetrazolium chloride stain) were assessed in sections of the left ventricle using image analysis. Groups of SNX rats also received: antihypertensive treatment (nadolol plus hydralazine); moxonidine; high salt diet or low salt diet (1.58% versus 0.015%). In surviving animals, the nonperfused area at risk (as the proportion of total left ventricular area), presumably determined by the geometry of vascular supply, was similar in sham-operated and SNX animals (0.38 +/- 0.13 versus 0.45 +/- 0.09; NS). In contrast, the infarcted area, given as a proportion of the nonperfused risk area, was significantly (P < 0.003) higher in SNX (0.68 +/- 0.09) compared with sham-operated (0.51 +/- 0.11) rats and was not altered by any of the above interventions. The finding that a greater proportion of nonperfused myocardium undergoes total necrosis is consistent with the hypothesis of reduced ischemia tolerance of the heart in renal failure. The findings could explain the high rate of death from MI in patients with impaired renal function.
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PMID:Increased infarct size in uremic rats: reduced ischemia tolerance? 1515 63

Replacement of injured endothelial cells by bone marrow derived endothelial progenitor cells (EPC's) is a new pathway of vascular repair after ischemia. Endothelial progenitor cells contribute less than 0.01% to the peripheral venous compartment of mononuclear cells. The detection of EPC's requires a demonstration of CD 34 and VEGFR-2 (vascular endothelial growth factor receptor-2) antigenic cell membrane determinants and proof of endothelial characteristics after outgrowth and differentiation in cell culture. The most important stimuli to the mobilization and proliferation of EPC's are VEGF, GM-CSF (granulocyte-macrophage colony stimulating factor), erythropoietin, HMG-CoA-reductase inhibitors and tissue ischemia. In vivo in patients EPC's appear to contribute to endothelialization of vascular grafts, the formation of collaterals of ischemic limbs and the healing of myocardial infarcts. The role of EPC's in uremia is currently under investigation.
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PMID:Role of endothelial progenitor cells in cardiovascular pathology. 1563 37

Accelerated atherosclerosis in dialysis patients is characterized by severe vascular calcification, and the magnitude of vascular calcification is associated with increased cardiovascular mortality. Calcification-dependent arterial stiffness is considered to be a major determinant of cardiac failure in uremia. Fetuin-A/alpha(2)-Heremans-Schmid glycoprotein is an abundant serum protein with powerful calcification inhibitory properties. Fetuin-A deficiency was recently linked to cardiovascular mortality in dialysis patients. Fetuin-A knockout (fetuin-KO) mice spontaneously develop widespread soft tissue calcification, including significant myocardial calcification, whereas larger arteries are spared. Therefore, this investigation offers the unique opportunity to study the functional role of isolated myocardial calcification independent of arterial stiffness by assessing the hemodynamics of fetuin-KO mice. Cardiac output in fetuin-KO mice was lower than in wild-type mice (fetuin-KO 1.81 +/- 0.18 versus WT 2.45 +/- 0.29 ml/min per g; P < 0.005), and fetuin-KO mice were refractory to dobutamine stimulation. Left ventricular relaxation was significantly impaired in fetuin-KO hearts with the relaxation index reduced by 23% (P < 0.005). After ischemia, fetuin-KO hearts displayed a continuous decline in left ventricular developed pressure after the initial phase of reperfusion, resulting in 77 +/- 15% of preischemic left ventricular developed pressure (P < 0.05 versus wild-type). In fetuin-KO mice, dystrophic cardiac calcification, with myocardial calcium contents increased 60-fold, was associated with profound induction of profibrotic TGF-beta and downstream collagen and fibronectin mRNA synthesis. In conclusion, independent of arterial stiffness, calcification-associated "myocardial stiffness" characterized by cardiac fibrosis, diastolic dysfunction, impaired tolerance to ischemia, and catecholamine resistance thus may constitute an underestimated cardiovascular risk factor that contributes to cardiac failure in calcification-prone states.
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PMID:Myocardial stiffness, cardiac remodeling, and diastolic dysfunction in calcification-prone fetuin-A-deficient mice. 1617

Cytochrome P450s (P450) metabolize arachidonic acid (AA) to hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs). Among these eicosanoids, 20-HETE is formed in a tissue and cell-specific fashion and plays an important role in the regulation of vascular tone in the brain, kidney, heart and splanchnic beds. 20-HETE is a potent vasoconstrictor produced in vascular smooth muscle (VSM) cells. It depolarizes VSM by blocking the open-state probability of Ca2+-activated K+-channels. Inhibitors of the formation of 20-HETE block the myogenic response of renal and cerebral arterioles in vitro and autoregulation of renal and cerebral blood flow in vivo. The formation of 20-HETE in vascular smooth muscle is stimulated by angiotensin II, endothelin and norepinephrine and is inhibited by nitric oxide (NO). 20-HETE also stimulates mitogenic and angiogenic responses in vitro and in vivo. Changes in the production of 20-HETE have been observed in ischemic cerebrovascular diseases, cardiac ischemia-reperfusion injury, kidney diseases, hypertension, diabetes, uremia, toxemia of pregnancy. The physiological and pathophysiological role of 20-HETE in the regulation of vascular tone are being revealed by the use of newly developed inhibitors of the synthesis of 20-HETE and 20-HETE analogs. The present review summarizes recent findings implicating a critical role for 20-HETE in altering cardiovascular function in a variety of pathological conditions.
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PMID:Role of 20-hydroxyeicosatetraenoic acid (20-HETE) in vascular system. 1625 32

Cardiac disease is the most common cause of death in patients with endstage renal disease. It was assumed that the high rate of cardiovascular mortality was based on accelerated atherosclerosis. Recently published articles, however, demonstrated that only 30-50% of all cardiac deaths in patients with uremia was due to myocardial infarction. On the other hand 30-40% of all patients with renal insufficiency, angina pectoris and documented ischemia have normal coronary arteries. Therefore, it is suggested that in patients with chronic uremia apart from accelerated atherosclerosis further abnormalities of the heart lead to myocardial ischemia. Recently published papers report functional and structural changes, which affect myocardial perfusion reserve. These structural changes include left ventricular hypertrophy, interstitial myocardial fibrosis, and microvascular disease.
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PMID:[Cardiac alterations caused by renal failure]. 1680 24

Acute kidney injury (AKI) is associated with significant mortality, which increases further when combined with acute lung injury. Experiments in rodents have shown that kidney ischemia-reperfusion injury (IRI) facilitates lung injury and inflammation. To identify potential ischemia-specific lung molecular pathways involved, we conducted global gene expression profiling of lung 6 or 36 h following 1) bilateral kidney IRI, 2) bilateral nephrectomy (BNx), and 3) sham laparotomy in C57BL/6J mice. Bronchoalveolar lavage fluid analysis revealed increased total protein, and lung histology revealed increased cellular inflammation following IRI, but not BNx, compared with sham controls. Total RNA from whole lung was isolated and hybridized to 430MOEA (22,626 genes) GeneChips (n = 3/group), which were analyzed by robust multichip average and significance analysis of microarrays and linked to gene ontology (GO) terms using MAPPFinder. The microarray power analysis predicted that the false discovery rate (q < 1%) and > or =50%-fold change compared with sham would represent significant changes in gene expression. Analysis identified 266 and 455 ischemia-specific, AKI-associated lung genes with increased expression and 615 and 204 with decreased expression at 6 and 36 h, respectively, compared with sham controls. Real-time PCR analysis validated select array changes in lung serum amyloid A3 and endothelin-1. GO analysis revealed significant activation (Z > 1.95) of several proinflammatory and proapoptotic biological processes. Ischemic AKI induces functional and transcriptional changes in the lung distinct from those induced by uremia alone. Further investigation using this lung molecular signature induced by kidney IRI will provide mechanistic insights and new therapies for critically ill patients with AKI.
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PMID:Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy. 1742 33


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