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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the complex mechanism(s) involved in molecular responses to ischemia, we developed two experimental models in pigs. In a "stunning" model of repetitive ischemia and reperfusion, we studied the mRNA expression of immediate early genes like c-fos, c-myc and heat shock protein-70 (HSP-70). Myocardial stunning was achieved by two cycles of 10-min left anterior descending coronary artery (LAD) occlusion and 30 min reperfusion. We observed several-fold enhanced expression of c-fos and HSP-70 mRNA in the stunned myocardium as compared with the control, whereas c-myc mRNA levels remained almost unchanged. In the second model, we examined the expression of the peptide mitogens heparin-binding growth factor 1 (HBGF-1) and transforming growth factor beta 1 (TGF-beta 1) after a chronic coronary artery occlusion leading to myocardial collateralization. Progredient stenosis of the circumflex coronary artery was induced by implanting a hygroscopic ameroid constrictor ring around it and occlusion was verified by in vivo angiography. Using polymerase chain reaction (PCR) and Northern hybridization techniques, we observed significantly enhanced expression of HBGF-1 and TGF-beta 1 in collateralized myocardium as compared with normal. In situ techniques revealed the localization of HBGF-1 transcripts in the blood vessel wall, and TGF-beta 1 in cardiac myocytes and Purkinje cells. Our results clearly indicate that myocardial stunning stimulates the expression of transcription factors which might be involved in regulation of certain growth factors like HBGF-1 and TGF-beta 1 which may play a significant role in the development of a collateral circulation.
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PMID:Molecular biology of the coronary vascular and myocardial responses to ischemia. 138 Jun 15

Cerebral ischemia induces the expression of a number of proteins that may have an important influence on cellular injury. The purpose of this study was to compare the regional effects of hypoxia-ischemia on the expression of the proto-oncogene, c-fos, and the heat shock protein-70 (HSP-70) gene in developing brain. Unilateral hypoxia-ischemia was produced in the brain of immature rats (7, 15, and 23 days after birth) using a combination of carotid artery ligation and systemic hypoxia (8% O2). After recovery for 2 and 24 h, the regional expression of c-fos and HSP-70 mRNA was determined using in situ hybridization. Littermates were permitted to recover for 1 week for assessment of histologic injury. Hypoxia-ischemia increased the expression of both c-fos and HSP-70 mRNA, but the topography of expression varied with the age of the animal as well as the mRNA species. In the 7-day-old group, expression of c-fos at 2 h increased in multiple regions of the ipsilateral hemisphere in nearly one-half of the animals, while HSP-70 mRNA was not expressed until 24 h and, then, predominantly in the hippocampus. In 15- and 23-day-old rats, expression of c-fos was increased at 2 h in the entorhinal cortex and in the dendritic field of the upper blade of the hippocampal dentate gyrus, while HSP-70 mRNA was prominently expressed in neocortex and the cell layers of the hippocampus. Interestingly, the strong expression of HSP-70 mRNA in dentate granule cells did not occur in the innermost layer of cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional expression of c-fos and heat shock protein-70 mRNA following hypoxia-ischemia in immature rat brain. 140 Jun 53

In situ hybridization was used to estimate regional levels of heat shock protein-70 (HSP-70) mRNA and c-fos mRNA in two related models of focal cerebral ischemia. In the first model, permanent occlusion of the distal middle cerebral artery (MCA) alone caused a patchy increase in HSP-70 mRNA by 1 h in the central zone of the MCA territory of the ipsilateral neocortex. Tissue levels of HSP-70 mRNA continued to increase for several hours and remained elevated at 24 h. In contrast to the focal expression of HSP-70, c-fos mRNA was increased throughout the ipsilateral cerebral cortex by 15 min and remained elevated for least 3 h. The wide distribution of c-fos expression suggests it may have been caused by spreading depression. In the second model, severe focal ischemia was produced with a combination of transient (1-h) bilateral carotid artery occlusion and permanent MCA occlusion. Combined occlusion for 1 h without reperfusion caused expression of HSP-70 mRNA only in regions adjacent to the central zone of the MCA territory of the neocortex. However, reperfusion of the carotids for 2 h generated intense expression of HSP-70 mRNA throughout most of the ipsilateral cerebral cortex, white matter, striatum, and hippocampus. The wide-spread increase in HSP-70 mRNA suggests that reperfusion triggered expression in all previously ischemic regions. However, at 24 h of reperfusion, increased levels of HSP-70 mRNA were restricted primarily to the ischemic core of the neocortex. These results suggest that expression of HSP-70 mRNA is prolonged in regions undergoing injury, but is transient in surrounding regions that recover.
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PMID:Regional expression of heat shock protein-70 mRNA and c-fos mRNA following focal ischemia in rat brain. 154 93

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the 'ischemic tolerance' phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of 'ischemic tolerance'.
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PMID:'Ischemic tolerance' phenomenon detected in various brain regions. 180 39

Adaptation of animals to short-term stress exposure (ASE) protected the heart against arrhythmias in acute ischemia and reperfusion and eliminated the decrease in threshold of fibrillation and arrhythmias is acute myocardial infarction and postinfarction cardiosclerosis. Cardioprotective effect of ASE was provided not only by the activation of GABAergic, opioidergic and cholinergic stress-limiting system but also by a mechanism formed at the level of heart itself. Isolated hearts of animals adapted to short-term stress exposure possessed a strikingly enhanced resistance to toxic doses of catecholamines, Ca2+, and to reperfusion damage following total ischemia. Contracture-inducing and arrhythmogenic effects of these factors and the release of CK into the perfusate were manifold reduced in ASE. Mitochondria and elements of SR Ca-pump isolated from the hearts of adapted animals were much more resistant to autolysis. This phenomenon of adaptive stabilization of structures (PhASS) was accompanied by the accumulation of HSP 71 and a simultaneous increase in the heart thermal stability. In the coronary artery ligation the PhASS lacked the anti-ischemic effect, but it provided a decrease of the necrotic zone by more than 40%, the ischemic zone being unchanged, due to its cytoprotective effect.
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PMID:Adaptive protection of the heart and stabilization of myocardial structures. 187 72

The effect of brief myocardial ischemia on the expression of heat shock protein (HSP 70) was examined in an in vivo rabbit model of myocardial ischemia using Northern blotting. Functional studies were carried out in the open-chested anesthetized rabbit. The large marginal branch of the left circumflex was occluded four times for 5 min. Using piezoelectric crystals implanted midwall in the ischemic zone, end-diastolic length, end-systolic length, and percent segmental shortening were assessed. Expression of HSP 70 was measured by Northern blotting. A single 5-min coronary occlusion doubled the expression of HSP 70 whereas four cycles of 5 min of ischemia/5 min of reperfusion resulted in a threefold increase in HSP 70 mRNA (P less than 0.001). Measurements with the piezoelectric crystals showed mild myocardial dysfunction concomitant with the increase in HSP 70. This increase in HSP 70 mRNA after repetitive brief ischemia was transient, occurring as early as 1 h and returning to baseline by 24 h after ischemia. Western blot analysis with a monoclonal antibody to HSP 70 was used to compare sham and postischemic myocardial HSP 70 levels. Changes in the amount of HSP 70 were evident as early as 2 h and were even more striking at 24 h.
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PMID:Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia. 198 91

Rats aged 7 days were exposed to 3.5 h of cerebral hypoxia-ischemia produced by unilateral common carotid artery ligation combined with hypoxia (8% oxygen). The major inducible heat-shock protein, HSP-68, was synthesized in ipsilateral but not contralateral (control) hippocampus during early recovery (1 and 3 h). HSP-68 synthesis was not detected during longer recovery periods. The presence of HSP-68 was confirmed by Western blotting and immunostaining with a polyclonal antibody to HSP-68.
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PMID:Synthesis of the major inducible heat shock protein in rat hippocampus after neonatal hypoxia-ischemia. 292 67

We examined the astrocytic GFAP and neuronal HSP-72 responses to transient middle cerebral artery (MCA) occlusion in the rat. Three groups of rats (n = 79) were studied: (1) fixed duration of MCA occlusion (120 min) and variable durations of reperfusion (0.5, 3, 6, 9, 12, 24, 48, 96 and 168 h); (2) variable durations of MCA occlusion (10, 20, 30, 60, 90, and 120 min) and a fixed duration of reperfusion (48 h); and (3) controls: sham operated rats and normal rats. Coronal sections from each brain were reacted with appropriate antibodies to GFAP and HSP-72 and stained with H&E for evaluation of cellular response to ischemia. Our data show that after MCA occlusion: (1) GFAP expression was found in the boundary zone to the infarct or in areas of selective incomplete ischemic necrosis; (2) GFAP expression was localized to the same areas where neurons express HSP-72 and are destined to survive the ischemic insult; and (3) HSP-72 expression was not found in astrocytes in any of the experimental groups. These studies suggest that after transient focal ischemia in the rat: areas where both GFAP and HSP-72 expression are lost are destined to become necrotic, even though cells may appear morphologically intact in the H&E preparations, and expression of GFAP and HSP-72 reflects astrocytic and neuronal viability, respectively.
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PMID:Expression of glial fibrillary acidic protein in areas of focal cerebral ischemia accompanies neuronal expression of 72-kDa heat shock protein. 773 89

It is apparent from the above discussion that acute stress, such as ischemia and reperfusion, hypoxia and reoxygenation, hyperthermia and oxidative stress, can rapidly potentiate the induction of genes for certain members of the HSP families and for antioxidants/antioxidant enzymes. Whether the stress response and induction of these genes have a direct role in myocardial protection is not known, but the induction of the expression of these genes are mostly associated with the preservation of myocardial cells from subsequent injury resulting from ischemia, hypoxia and reperfusion. The ubiquitous presence of some of these stress genes, such as for HSP 70 and catalase, in normal unstressed myocardium further suggests a role of these genes in many basic and essential biochemical and metabolic pathways. It is reasonable to speculate that the cells respond to the stress as a consequence of perturbations of one or more of the metabolic pathways by stimulating the induction of the stress genes of that particular pathway in which they participate. Thus, these genes are likely to be involved both in the protection and recovery/repair mechanisms. The precise mechanism by which myocardial cell recognizes and responds to a particular stress agent such as ischemia, hypoxia, hyperthermia or oxidative stress is not clear. While it is tempting to speculate that a generalized mechanism exists, applying to all different modes of stress response and gene induction, whether these agents induce the response via independent pathways or converge within a single point is entirely unclear. However, from the striking resemblance between the pattern of gene expression, especially with regard to HSP and antioxidant genes, it is reasonable to hypothesize the existence of a common and essential pathway of molecular signaling that leads to the expression of these stress genes (Fig. 2). The identification and characterization of the transcription factors that regulate the expression of the genes induced by these forms of stress should greatly facilitate our future understanding of the mechanism of stress response.
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PMID:Gene expression in acute myocardial stress. Induction by hypoxia, ischemia, reperfusion, hyperthermia and oxidative stress. 776 Mar 41

Ischemia/reperfusion (I/R) and preconditioning of the heart by coronary artery occlusions increase expression of heat shock protein 70 (HSP 70). Because free radicals are generated during I/R, we hypothesized that the oxidant stress might contribute to an increased expression of HSP 70. Isolated rat hearts were perfused with free radical-generating systems such as xanthine/xanthine oxidase (X/XO), irradiated rose bengal (RB) generating singlet oxygen, and H2O2 for 15 min followed by 30 min of recovery period. Significant decrease in developed pressure and coronary flow occurred after perfusion with X/XO, H2O2, and RB. During I/R, the developed pressure and coronary flow were 60 +/- 8 and 80 +/- 5%, respectively, of control, which improved significantly with superoxide dismutase. The expression of HSP 70 mRNA increased over 13-fold in hearts perfused with X/XO, 6- to 7-fold with RB, and over 5-fold with H2O2. With I/R, an over 10-fold increase in HSP 70 mRNA was observed, which decreased significantly in the presence of superoxide dismutase. These results demonstrate that oxidant stress directly increases HSP 70 mRNA in the rat heart. It is concluded that one of the potential mechanisms of expression of HSP 70 by I/R may be oxygen radicals.
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PMID:Oxidant stress increases heat shock protein 70 mRNA in isolated perfused rat heart. 781 Jul 20


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