Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute ischemia is a well-known inductor of extracellular matrix (ECM) remodeling, which leads to the development of congestive heart failure and is associated with left ventricular dilatation. Here we investigate the timecourse of ECM processing with release of endostatin (ES) and other low-molecular-weight fragments during early ischemia-reperfusion of the heart. In this blinded study, 30 pigs were randomized to 60 min of global myocardial ischemia at either 4 or 37 degrees C or served as control. Five transmyocardial tissue samples were collected at baseline and after ischemia within 150 min of reperfusion. Collagen XVIII cleavage products of 10-75 kDa including ES (25 kDa) were analyzed using the Western blot and ELISA method, and creatin kinase as marker of myocardial injury was determined in samples collected from the coronary sinus. We demonstrate that processing of the extracellular matrix protein collagen XVIII starts during early reperfusion, as we observed a significantly increased expression of cleavage products at 10 and 75 kDa as well as ES at 150 min of normothermic ischemia-reperfusion. We further demonstrate a differential processing of collagen XVIII depending on temperature conditions during myocardial ischemia, as an increase in cleavage products was observed after normothermic ischemia only; however, expression of ES and other fragments remained unchanged after hypothermic ischemia-reperfusion and in controls. In conclusion, this blinded study first demonstrated that processing of extracellular matrix started early after ischemia-reperfusion and depends on temperature conditions. These findings may contribute to a broader understanding of matrix processing after ischemia-reperfusion.
 ...
PMID:Ischemia-reperfusion injury activates early extracellular matrix processing and expression of endostatin in the heart with differential effects of temperature. 1925

Prolyl hydroxylases are members of the iron- and 2-oxoglutarate-dependent dioxygenase enzyme family. Collagen prolyl hydroxylase is well known for its involvement in scurvy, in which ascorbate deficiency inhibits the enzyme and results in characteristic signs of the disease. Several distinct prolyl hydroxylases that hydroxylate (and thereby regulate) the hypoxia-inducible factor (HIF) transcription factors were discovered in 2001. These HIF prolyl hydroxylases, termed prolyl hydroxylase domain enzymes (PHDs), are the subject of this forum. HIF coordinates the cellular response to hypoxia, and the PHDs have attracted widespread interest as potential therapeutic targets in a wide range of diseases including anemia, ischemic heart disease, stroke, cancer, and pulmonary hypertension. Novel PHD-based pharmaceutical agents are now undergoing clinical trials. As well as original data, this forum includes reviews discussing recent advances in the biochemistry and therapeutic manipulation of PHDs, the potential role of PHD inhibitors in neuroprotection, and the involvement of PHDs in the complex interaction between oxygen homeostasis and iron homeostasis.
 ...
PMID:Prolyl hydroxylases and therapeutics. 1976 7

Early healing after myocardial infarction (MI) is characterized by a strong inflammatory reaction. Most leukotrienes are pro-inflammatory and are therefore potential mediators of healing and remodeling after myocardial ischemia. The enzyme 5-lipoxygenase (5-LOX) has a key role in the transformation of arachidonic acid in leukotrienes. Thus, we tested the effect of 5-LOX on healing after MI. After chronic coronary artery ligation, early mortality was significantly increased in 5-LOX(-/-) when compared to matching wildtype (WT) mice due to left ventricular rupture. This effect could be reproduced in mice treated with the 5-LOX inhibitor Zileuton. A perfusion mismatch due to the vasoactive potential of leukotrienes is not responsible for left ventricular rupture since local blood flow assessed by magnetic resonance perfusion measurements was not different. However, after MI, there was an accentuation of the inflammatory reaction with an increase of pro-inflammatory macrophages. Yet, mortality was not changed in chimeric mice (WT vs. 5-LOX(-/-) bone marrow in 5-LOX(-/-) animals), indicating that an altered function of 5-LOX(-/-) inflammatory cells is not responsible for the phenotype. Collagen production and accumulation of fibroblasts were significantly reduced in 5-LOX(-/-) mice in vivo after MI. This might be due to an impaired migration of 5-LOX(-/-) fibroblasts, as shown in vitro to serum. In conclusion, a lack or inhibition of 5-LOX increases mortality after MI because of healing defects. This is not mediated by a change in local blood flow, but through an altered inflammation and/or fibroblast function.
...
PMID:5-Lipoxygenase facilitates healing after myocardial infarction. 2381 48

A great body of evidence has shown that extracellular matrix (ECM) alterations are present in the major types of cardiac diseases: ischemic heart disease, heart disease associated with pressure overload, heart disease associated with volume overload, and intrinsic myocardial disease or cardiomyopathy. Collagen, type I and III, is the principal structural protein found in the myocardium and its pro- or telopeptides are released into the circulation during the course of cardiovascular diseases. Therefore, these peptides may reflect collagen synthesis and break-down and also represent a much more useful tool to address ECM changes from a distance. Clinical trials have been performed during recent years to examine the usage of these peptides as diagnostic or prognostic biomarkers in heart failure (HF) patients. This review aims to summarize published data concerning cardiac ECM and its circulating biomarkers. Studies that focused on collagen metabolism related biomarkers in patients with HF are analyzed. Finally, limitations associated with the clinical use of the aforementioned biomarkers are also discussed.
...
PMID:Biomarkers of the extracellular matrix and of collagen fragments. 2500 52

The collagen matrix of the heart forms a network linking muscle fibers, muscle bundles, and intramyocardial blood vessels. Collagen turnover in the heart is normally a dynamic process that involves both collagen synthesis and degradation. Collagen breakdown generally involves its chemical digestion by matrix metalloproteinases (MMPs) which are activated in tissue repair, wound healing, and myocardial ischemia. We studied activation of MMPs by zymography in infarct (anterolateral wall) and non-infarct (septum) zones of rat hearts following coranary artery ligation, as well as in sham operated rats. Rats were sacrificed at 30 minutes, 1 hour, 2 hours, 4 hours, and 24 hours post infarction (six hearts for each time period). MMP activity was detected at different molecular weights, with bands at 54 kDa (MMP-1), 62 kDa (MMP-2), and 92 kDa (MMP-9) being the most prominent. MMP activities were indexed by densitometer optical reading. Activity was detected as early as 1 hour post infarct in the MI and remote zones at the 54 kDa (MMP-1) ( p < 0.01) and 62 kDa bands (MMP-2) ( p < 0.001), and at 2 hours post infarct in the infarct zone only at 92 kDa (MMP-9) ( p < 0.05). MMPs are activated early after infarction both in the infarct and importantly, non-infarct zones. This may contribute to collagen breakdown, infarct expansion, and left ventricular remodeling, known to occur early after infarction in experimental and clinical settings.
...
PMID:Early Activation of Metalloproteinases after Experimental Myocardial Infarction Occurs in Infarct and Non-infarct Zones. 2585 97

Mining data in depth of genome-wide sequencing data generated from pathological target tissues under disease conditions is necessary for seeking novel functional genes, and developing more biological study directions for the field. Based on our previous published RNA-seq data generated from acute myocardial ischemia and ischemia-reperfusion in rat heart, we re-analysed these two data sets using bioinformatics tools. All these raw fastq files were extracted from Illumina BCL using the Illumina CASAVA program. Four groups were obtained: UD (genes up-regulated in MI but down-regulated in I/R injury), DU (genes down-regulated in MI but up-regulated in I/R injury), UU (genes both up-regulated in MI and I/R injury), and DD (genes both down-regulated in MI and I/R injury) groups. The results showed that 304 common genes in the UD group, 236 common genes in the DU group, 318 common genes in the UU group, and 159 common genes in the DD group detected by comparing data sets of the MI and the I/R injury. We then listed the top 30 DEGs for each group, and carried out GO and KEGG analyses for enrichment and pathway studies for those top expressed genes. Further analysis of INTERPRO Protein Domains and Features enriched by DEGs showed that 20% of the Domains enriched were related to c-type lectin, and 17% of these domains are related to neurotransmitter-gated ion-channel. 15% of PFAM Protein Domains were about Neurotransmitter-gated ion-channel. There were only 8 SMART Protein Domains DEGs enriched and 37.5% of which were concerned about leucine-rich. Collagen involvement in Reactome Pathways accounted for 22.7%. We found that only a few DEGs in these two disease conditions have been reported in the literatures, suggesting that there are many new genes would be considered in the future studies. These analyses would provide some information for seeking more novel targets of these two clinic diseases, acute myocardial ischemia and myocardial ischemia/reperfusion.
 ...
PMID:Comparative study of gene expression profiles rooted in acute myocardial infarction and ischemic/reperfusion rat models. 3268 66


<< Previous 1 2