Hypothesized pathways in pathogenesis of cardiovascular disease (Homo sapiens)

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1TGFB ligands, Receptors, Activators, EffectorsTarget gene expressionMAPK8NR2C2Development and maintenance of cardiovascular structure and functionRUNX2SMAD2LTBP1ENGTGFBR3FBN1TGFBR1Calcium calneurin pathwayANG2MAPK3MAPK14SMAD3MAPK1SHC1Heart valve diseaseEndocardial and epicardial EMTCTGFTGFBR2ECM remodelingPOSTNSERPINE1SMAD4AGTR1PPFBN2FBN3LTBP2FLNAActin cytoskeletonSMAD2PSMAD3PCardiomyopathyAortic aneurysmHypertensionAtherosclerosisKawasaki diseaseNeural crest migrationCell differentiation


Description

The pathways hypothesized to be involved in cardiovascular diseases begin with LTBPs and fibrillins activating a TGFBR complex. The complex can begin the canonical TGFB pathway involving SMAD proteins that target gene expression for proteins involved in endocardial and epicardial EMT, neural crest migration, ECM remodeling, cell differentiation, development and maintenance of cardiovascular structure and function. The non-canonical TGFB pathway involves the calcium-calneurin signaling pathway that also affects those functions. The TGFBR complex also activates SHCA and Tak1, which promote the function of a complex (ERK1/2, JNK1, and p38) to regulate the previously mentioned cell functions and influence the development of cardiovascular diseases. These diseases are additionally influenced by a signaling pathway involving the activation of TGFB ligands, receptors, activators, and effectors by ANG2/AT1/2R complex. This pathway is based on figure 1 from Doetschman et al.


Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Ontology Terms

 

Bibliography

  1. Doetschman T, Barnett JV, Runyan RB, Camenisch TD, Heimark RL, Granzier HL, Conway SJ, Azhar M; ''Transforming growth factor beta signaling in adult cardiovascular diseases and repair.''; Cell Tissue Res, 2012 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
128974view23:45, 25 February 2024EweitzColor biological process nodes with #088, economize layout
128973view23:42, 25 February 2024EweitzVisually distinguish biological process nodes via #077, rounding
128972view23:29, 25 February 2024EweitzNodulize biological processes
128971view23:09, 25 February 2024EweitzModified description
128970view23:02, 25 February 2024EweitzOntology Term : 'endocardial cell' added !
128969view23:00, 25 February 2024EweitzUpgrade disease nodes
128968view22:24, 25 February 2024EweitzOntology Term : 'Kawasaki disease' added !
128967view22:24, 25 February 2024EweitzOntology Term : 'atherosclerosis' added !
128966view22:23, 25 February 2024EweitzOntology Term : 'hypertension' added !
128965view22:23, 25 February 2024EweitzOntology Term : 'aortic aneurysm' added !
128964view22:21, 25 February 2024EweitzOntology Term : 'cardiomyopathy' added !
128963view22:20, 25 February 2024EweitzOntology Term : 'cardiomyopathy pathway' added !
128962view22:20, 25 February 2024EweitzOntology Term : 'heart valve disease' added !
128961view20:03, 25 February 2024EweitzFix invalid pathway node, standardize case
123393view06:23, 23 July 2022EgonwRemoved an "N/A" identifier
117756view12:52, 22 May 2021EweitzModified title
108207view11:12, 29 November 2019FehrhartOntology Term : 'disease pathway' added !
106596view19:35, 10 September 2019KhanspersModified description
105620view04:58, 10 August 2019KhanspersModified description
97639view14:21, 31 May 2018AMTanOntology Term : 'cardiovascular system disease' added !
90185view18:37, 21 October 2016Khanspersfixed unconnected
90100view17:38, 13 October 2016Khanspersupdate
88723view19:15, 12 August 2016AAR&CoAdded Data Nodes
88722view19:06, 12 August 2016AAR&CoPeriodical save, work in progress
88721view18:43, 12 August 2016AAR&CoEdited Interactions and Labels
88720view18:40, 12 August 2016AAR&CoPeriodical save, work in progress
88655view15:13, 12 August 2016JmeliusOntology Term : 'cardiovascular system disease pathway' added !
85961view20:03, 21 June 2016AAR&CoModified description
85960view19:58, 21 June 2016AAR&CoModified description
85959view19:55, 21 June 2016AAR&CoEditing Interactions
85958view19:53, 21 June 2016AAR&CoEditing Cell Positioning
85957view19:51, 21 June 2016AAR&CoNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AGTR1GeneProductENSG00000144891 (Ensembl) Identifier Not Found
ANG2GeneProductENSG00000091879 (Ensembl)
Aortic aneurysmQ616003 (Wikidata)
AtherosclerosisQ12252367 (Wikidata)
CTGFGeneProductENSG00000118523 (Ensembl)
Calcium calneurin pathwayPathway
CardiomyopathyQ847583 (Wikidata)
Cell differentiationQ210861 (Wikidata)
Development and maintenance

of cardiovascular structure

and function
ECM remodeling
ENGGeneProductENSG00000106991 (Ensembl)
Endocardial and epicardial EMTQ14883191 (Wikidata)
FBN1GeneProductENSG00000166147 (Ensembl) Firbrillins Not Specified
FBN2GeneProductENSG00000138829 (Ensembl) Firbrillins Not Specified
FBN3GeneProductENSG00000142449 (Ensembl) Firbrillins Not Specified
FLNAGeneProductENSG00000196924 (Ensembl)
Heart valve diseaseQ1130519 (Wikidata)
HypertensionQ41861 (Wikidata)
Kawasaki diseaseQ265936 (Wikidata)
LTBP1GeneProductENSG00000049323 (Ensembl) LTBP Not Specified
LTBP2GeneProductENSG00000119681 (Ensembl) LTBP Not Specified
MAPK14GeneProductENSG00000112062 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MAPK8GeneProductENSG00000107643 (Ensembl)
NR2C2GeneProductENSG00000177463 (Ensembl)
Neural crest migrationGO:0001755 (Other)
POSTNGeneProductENSG00000133110 (Ensembl)
RUNX2GeneProductENSG00000124813 (Ensembl)
SERPINE1GeneProductENSG00000106366 (Ensembl)
SHC1GeneProductENSG00000160691 (Ensembl)
SMAD2GeneProductENSG00000175387 (Ensembl)
SMAD3GeneProductENSG00000166949 (Ensembl)
SMAD4GeneProductENSG00000141646 (Ensembl)
TGFBR1GeneProductENSG00000106799 (Ensembl)
TGFBR2GeneProductENSG00000163513 (Ensembl)
TGFBR3GeneProductENSG00000069702 (Ensembl)

Annotated Interactions

No annotated interactions

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