Hypothesized pathways in pathogenesis of cardiovascular disease (Homo sapiens)

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1Valvular Heart DiseaseCardiomyopathyAortic AneurysmHypertensionAtherosclerosisKawasaki DiseaseTGFB Ligands, Receptors, Activators, EffectorsTarget Gene ExpressionEndocardial and Epicardial EMT, neural crest migration, ECM remodeling, cell differentiation,development and maintenance of cardiovascular structure and functionTGFBR2LTBPsp38SHCACTGFSMAD4PeriostinSMAD3TGFBR3ERK1RUNX2ERK2FibrillinsTGFBR1SMAD2JNK1EndoglinCalcium Calneurin PathwayAT1/2RPAI-1ANG2Tak1


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 the previously mentioned 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 signalling 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.

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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

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NameTypeDatabase referenceComment
ANG2GeneProductENSG00000091879 (Ensembl)
AT1/2RGeneProductIdentifier Not Found
CTGFGeneProductENSG00000118523 (Ensembl)
Calcium Calneurin PathwayPathwayN/A (WikiPathways) Identifer Not Found
ERK1GeneProduct5595 (NCBI Protein)
ERK2GeneProduct5594 (NCBI Protein)
EndoglinProteinF5GX88 (Uniprot-TrEMBL)
FibrillinsProteinF6U495 (Uniprot-TrEMBL) Firbrillins Not Specified
JNK1GeneProduct5599 (NCBI Protein)
LTBPsGeneProductENSG00000049323 (Ensembl) LTBP Not Specified
PAI-1ProteinQ5VU21 (Uniprot-TrEMBL)
PeriostinProteinB1ALD9 (Uniprot-TrEMBL)
RUNX2GeneProductENSG00000124813 (Ensembl)
SHCAGeneProduct6464 (NCBI Protein)
SMAD2GeneProductENSG00000175387 (Ensembl)
SMAD3GeneProductENSG00000166949 (Ensembl)
SMAD4GeneProductENSG00000141646 (Ensembl)
TGFBR1GeneProductENSG00000106799 (Ensembl)
TGFBR2GeneProductENSG00000163513 (Ensembl)
TGFBR3GeneProductENSG00000069702 (Ensembl)
Tak1GeneProduct7182 (NCBI Protein)
p38GeneProduct1432 (NCBI Protein)

Annotated Interactions

No annotated interactions

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