Corticosteroid Cardioprotection Pathway

Preferred Label : Corticosteroid Cardioprotection Pathway;

NCIt related terms : Corticosteroids and cardioprotection;

Alternative definition : BIOCARTA: Myocardial infarction damages heart tissue both during the initial ischemia and the subsequent reperfusion of tissues with oxygen. Corticosteroids can protect cardiac tissue from damage following a heart attack, but the mechanisms by which corticosteroids are cardioprotective have not been clear and negative side effects such as reduced wound healing may result from their use. Corticosteroids exert a variety of actions through binding to the glucocorticoid receptor (GR), a member of the steroid hormone receptor gene family. GR acts as a ligand-dependent transcription factor, but some of the cardioprotective effects mediated by GR-bound corticosteroids are non-transcriptional in nature. Glucocorticoids are commonly used as anti-inflammatory drugs in a variety of conditions, and some of their effects in the heart result from inhibition of the inflammatory response of heart tissue to ischemia and reperfusion. NF-kB is a transcription factor involved in signaling by inflammatory factors such as TNF, and is repressed by glucocorticoids. Annexin-1 is a calcium-dependent phospholipid binding protein whose expression is induced by corticosteroids and inhibits the infiltration of neutrophils into tissue, blocking reperfusion-induced inflammatory heart damage. A non-transcriptional cardioprotective effect of glucocorticoids is activation of NO production by endothelial nitric oxide synthase (eNOS). Glucocorticoids activate eNOS through activation of PI3 kinase and AKT and increased NO produced by eNOS can diffuse into surrounding tissues to prevent clotting and cause vasodilation. The beta-2 adrenergic receptor can also activate PI3 kinase and may synergize with glucocorticoids in this pathway. The atrial natriuretic factor (ANF) is a peptide secreted by the atrial wall in response to increased atrial pressure such as occurs during cardiac failure and to be decreased by myocardial infarction. Glucocorticoids increase the secretion of ANF by acting at the transcriptional level to increase expression of the pro-ANF peptide, perhaps inducing increased water excretion in the kidneys to reduce blood volume and reduce atrial pressure. The exploration of glucocorticoid responses may allow the identification of compounds that retain the cardioprotective activities but do not inhibit wound healing. Alternative mechanisms of eNOS activation may also provide a route to identify cardioprotective drugs. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_gcrPathway;

Details

Origin ID

C39091;

UMLS CUI

C1511530;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- 3-Phosphoinositide-Dependent Protein Kinase 1 [NCIt concept]
- Atrial Natriuretic Factor [NCIt concept]
- B2 Bradykinin Receptor [NCIt concept]
- Beta-2 Adrenergic Receptor [NCIt concept]
- Caveolin-1 [NCIt concept]
- Glucocorticoid Receptor [NCIt concept]
- Guanine Nucleotide-Binding Protein G(s) Subunit Alpha Isoforms Short [NCIt concept]
- Guanine Nucleotide-Binding Protein G(s) Subunit Alpha Isoforms XLas [NCIt concept]
- Heat Shock Protein HSP 90-Alpha [NCIt concept]
- Nitric Oxide Synthase, Endothelial [NCIt concept]
- Phosphatidylinositol 3-Kinase Regulatory Subunit Alpha [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Isoform [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma Isoform [NCIt concept]
- RAC-Alpha Serine/Threonine Kinase [NCIt concept]
- Transcription Factor p65 [NCIt concept]
pathway_has_gene_element
- ADRB2 wt Allele [NCIt concept]
- AKT1 wt Allele [NCIt concept]
- BDKRB1 wt Allele [NCIt concept]
- BDKRB2 wt Allele [NCIt concept]
- CAV1 wt Allele [NCIt concept]
- GNAS wt Allele [NCIt concept]
- HSP90AA1 wt Allele [NCIt concept]
- NOS3 wt Allele [NCIt concept]
- NPPA wt Allele [NCIt concept]
- NR3C1 wt Allele [NCIt concept]
- PDPK1 wt Allele [NCIt concept]
- PIK3CA wt Allele [NCIt concept]
- PIK3CG wt Allele [NCIt concept]
- PIK3R1 wt Allele [NCIt concept]
- RELA wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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