loading...| Preferred Name |
Myocardial Infarction |
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| Synonyms |
PathwayType: signaling PMID: 21091074 Organ_System: cardiovascular system PMID: 23824949 PMID: 17991891 Notes: Headnote: Myocardial infarction (MI) results from prolonged ischemia or the interruption of coronary blood supply to a part of the heart resulting in death of the heart muscle. If blood flow is not restored to the heart muscle within 20 to 40 minutes, irreversible death of the heart muscle will begin to occur. Signaling description: Following MI, the dead heart muscle is eventually replaced by scar tissue. The maintenance of cardiac function is determined by cardiomyocyte death and recovery.The most common symptom of a heart attack is chest pain and important risk factors include: previous cardiovascular disease, older age, tobacco smoking, high blood pressure, high levels of cholesterol, diabetes, lack of physical activity and obesity, chronic kidney disease, excessive alcohol consumption, and long-term stress. Necrosis, apoptosis, and autophagy contribute to the death of cardiomyocytes. Apoptosis is a highly regulated process activated via death receptors in the plasma membrane or mitochondria permeabilization. Necrosis is generally an uncontrolled process that leads to mitochondrial swelling, cell rupture, and subsequent inflammation. Mitochondria play an important role in both apoptosis and necrosis and changes in their morphology can affect the susceptibility of cardiomyocytes to stress. Autophagy is an intracellular lysosomal degradative process. Ischemia leads to myocardial injury, and the following rapid release of HSPD1 and HMGB1from myocardium activate TLR4 and the advanced glycosylation end product specific receptor (AGER) signaling. Outcome effects: TLR4 signaling triggers the expression of a number of genes through the MYD88-dependent and TICAM-dependent pathways. TLR4-MYD88 signaling pathway leads to NF-kB activation via the IRAK4/IRAK1/TRAF6 axis. Further, NF-kB activates the BIRC2/BIRC3/BIRC5/XIAP complex, which prevents apoptosis; however, the activated DIABLO inhibits BIRC2 and XIAP, thus inducing apoptosis. In addition, the TLR4-TICAM and TNFRSF1A signaling pathways result in the activation of CASP9/CASP3 via MAP kinases (MAPKs). Outcome effects: Activated AGER participates in cardiomyocyte apoptosis through the activation of MAPK3/MAPK1 and autophagy through the activation of ATG13. Oxidative stress and acidification induce Ca2+ release, which, in turn induces oxidative stress leading to the generation of ROS, opening of mitochondrial permeability transition pores (mPTP), loss of mitochondrial membrane potential, release of CYCS from mitochondria, and activation of CASP9 and CASP3 involved in cardiomyocyte apoptosis and necrosis. In addition, ischemia and the presense of unfolded proteins promote endoplasmic reticulum (ER) stress. ER stress plays an important role in the progression of cardiovascular diseases including ischemic MI, as it causes the accumulation of misfolded proteins in the ER lumen, which attract chaperones such as HSPA5. Then, HSPA5 interacts with important ER transmembrane proteins including HSP90B1, EIF2AK3, ATF6, and ERN1. HSP90B1 facilitates ER-associated protein degradation via CANX. EIF2AK3, ATF6, and ERN1 induce apoptosis via ATF4 and XBP1. Highlighted proteins: Entities with increased levels are highlighted in red, and entities with decreased levels are highlighted in blue. Description: Myocardial infarction results from prolonged ischemia or the interruption of coronary blood supply to a part of the heart resulting in death of the heart muscle. Pathway is built manually using published studies. PMID: 15539639 Tissue: myocardium CellType: cardiac myocyte NodeType: Pathway Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-d40d1d40-940f-4dfd-8c48-1fbc7c92bda7 Organ: heart Pathway_Author: M. Zharkova ORCID:0000-0001-8706-9411 Source: Diseases |
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| ID |
urn:agi-pathway:uuid-d40d1d40-940f-4dfd-8c48-1fbc7c92bda7 |
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| database_cross_reference |
PS:PathwayType PS:Description PS:Tissue PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
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| has_exact_synonym |
PathwayType: signaling PMID: 21091074 Organ_System: cardiovascular system PMID: 23824949 PMID: 17991891 Notes: Headnote: Myocardial infarction (MI) results from prolonged ischemia or the interruption of coronary blood supply to a part of the heart resulting in death of the heart muscle. If blood flow is not restored to the heart muscle within 20 to 40 minutes, irreversible death of the heart muscle will begin to occur. Signaling description: Following MI, the dead heart muscle is eventually replaced by scar tissue. The maintenance of cardiac function is determined by cardiomyocyte death and recovery.The most common symptom of a heart attack is chest pain and important risk factors include: previous cardiovascular disease, older age, tobacco smoking, high blood pressure, high levels of cholesterol, diabetes, lack of physical activity and obesity, chronic kidney disease, excessive alcohol consumption, and long-term stress. Necrosis, apoptosis, and autophagy contribute to the death of cardiomyocytes. Apoptosis is a highly regulated process activated via death receptors in the plasma membrane or mitochondria permeabilization. Necrosis is generally an uncontrolled process that leads to mitochondrial swelling, cell rupture, and subsequent inflammation. Mitochondria play an important role in both apoptosis and necrosis and changes in their morphology can affect the susceptibility of cardiomyocytes to stress. Autophagy is an intracellular lysosomal degradative process. Ischemia leads to myocardial injury, and the following rapid release of HSPD1 and HMGB1from myocardium activate TLR4 and the advanced glycosylation end product specific receptor (AGER) signaling. Outcome effects: TLR4 signaling triggers the expression of a number of genes through the MYD88-dependent and TICAM-dependent pathways. TLR4-MYD88 signaling pathway leads to NF-kB activation via the IRAK4/IRAK1/TRAF6 axis. Further, NF-kB activates the BIRC2/BIRC3/BIRC5/XIAP complex, which prevents apoptosis; however, the activated DIABLO inhibits BIRC2 and XIAP, thus inducing apoptosis. In addition, the TLR4-TICAM and TNFRSF1A signaling pathways result in the activation of CASP9/CASP3 via MAP kinases (MAPKs). Outcome effects: Activated AGER participates in cardiomyocyte apoptosis through the activation of MAPK3/MAPK1 and autophagy through the activation of ATG13. Oxidative stress and acidification induce Ca2+ release, which, in turn induces oxidative stress leading to the generation of ROS, opening of mitochondrial permeability transition pores (mPTP), loss of mitochondrial membrane potential, release of CYCS from mitochondria, and activation of CASP9 and CASP3 involved in cardiomyocyte apoptosis and necrosis. In addition, ischemia and the presense of unfolded proteins promote endoplasmic reticulum (ER) stress. ER stress plays an important role in the progression of cardiovascular diseases including ischemic MI, as it causes the accumulation of misfolded proteins in the ER lumen, which attract chaperones such as HSPA5. Then, HSPA5 interacts with important ER transmembrane proteins including HSP90B1, EIF2AK3, ATF6, and ERN1. HSP90B1 facilitates ER-associated protein degradation via CANX. EIF2AK3, ATF6, and ERN1 induce apoptosis via ATF4 and XBP1. Highlighted proteins: Entities with increased levels are highlighted in red, and entities with decreased levels are highlighted in blue. Description: Myocardial infarction results from prolonged ischemia or the interruption of coronary blood supply to a part of the heart resulting in death of the heart muscle. Pathway is built manually using published studies. PMID: 15539639 Tissue: myocardium CellType: cardiac myocyte NodeType: Pathway Organ: heart Pathway_Author: M. Zharkova ORCID:0000-0001-8706-9411 Source: Diseases |
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| id |
urn:agi-pathway:uuid-d40d1d40-940f-4dfd-8c48-1fbc7c92bda7 |
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| label |
Myocardial Infarction |
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| notation |
uuid-d40d1d40-940f-4dfd-8c48-1fbc7c92bda7 |
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| prefLabel |
Myocardial Infarction |
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| treeView |
urn:agi-folder:cardiovascular_system urn:agi-folder:endoplasmic_reticulum urn:agi-folder:mitochondria urn:agi-folder:m urn:agi-folder:myocardial_ischemia urn:agi-folder:myocardium |
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| subClassOf |
urn:agi-folder:cardiovascular_system urn:agi-folder:endoplasmic_reticulum urn:agi-folder:mitochondria urn:agi-folder:m urn:agi-folder:myocardial_ischemia urn:agi-folder:myocardium |