Hypothesized Pathways in Pathogenesis of Cardiovascular Disease (Homo sapiens)

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1Endocardial and Epicardial EMT, neural crest migration, ECM remodeling, cell differentiation,development and maintenance of cardiovascular structure and functionValvular Heart DiseaseCardiomyopathyAortic AneurysmHypertensionAtherosclerosisKawasaki DiseaseTGFB Ligands, Receptors, Activators, EffectorsTarget Gene ExpressionTGFBR3ENGPOSTNNR2C2ANG2SERPINE1CTGFSHC1MAPK8RUNX2SMAD2AGTR1FBN1MAPK14TGFBR1MAPK1TGFBR2SMAD4MAPK3Calcium Calneurin PathwayLTBP1SMAD3PFBN2PFBN3LTBP2FLNAActin CytoskeletonSMAD2PSMAD3P


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.

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

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Ontology Terms



  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


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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


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NameTypeDatabase referenceComment
AGTR1GeneProductENSG00000144891 (Ensembl) Identifier Not Found
ANG2GeneProductENSG00000091879 (Ensembl)
CTGFGeneProductENSG00000118523 (Ensembl)
Calcium Calneurin PathwayPathwayN/A (WikiPathways) Identifer Not Found
ENGGeneProductENSG00000106991 (Ensembl)
FBN1GeneProductENSG00000166147 (Ensembl) Firbrillins Not Specified
FBN2GeneProductENSG00000138829 (Ensembl) Firbrillins Not Specified
FBN3GeneProductENSG00000142449 (Ensembl) Firbrillins Not Specified
FLNAGeneProductENSG00000196924 (Ensembl)
LTBP1GeneProductENSG00000049323 (Ensembl) LTBP Not Specified
LTBP2GeneProductENSG00000119681 (Ensembl) LTBP Not Specified
MAPK14GeneProductENSG00000112062 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MAPK8GeneProductENSG00000107643 (Ensembl)
NR2C2GeneProductENSG00000177463 (Ensembl)
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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