Hypothesized pathways in pathogenesis of cardiovascular disease (WP3668)

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 [https://assays.cancer.gov/available_assays?wp_id=WP3668 CPTAC Assay Portal]
last edited


AAR&Co, Jmelius, Khanspers, AMTan, Fehrhart, and Eweitz

Cited In


Homo sapiens




Pathway Ontology: cardiovascular system disease pathway disease pathway

Disease Ontology: cardiovascular system disease


Label Type Compact Identifier
MAPK3 GeneProduct ensembl:ENSG00000102882
Calcium Calneurin Pathway Pathway wikipathways:N/A
SMAD4 GeneProduct ensembl:ENSG00000141646
MAPK8 GeneProduct ensembl:ENSG00000107643
MAPK1 GeneProduct ensembl:ENSG00000100030
TGFBR2 GeneProduct ensembl:ENSG00000163513
POSTN GeneProduct ensembl:ENSG00000133110
SHC1 GeneProduct ensembl:ENSG00000160691
RUNX2 GeneProduct ensembl:ENSG00000124813
FBN1 GeneProduct ensembl:ENSG00000166147
CTGF GeneProduct ensembl:ENSG00000118523
NR2C2 GeneProduct ensembl:ENSG00000177463
LTBP1 GeneProduct ensembl:ENSG00000049323
MAPK14 GeneProduct ensembl:ENSG00000112062
ANG2 GeneProduct ensembl:ENSG00000091879
ENG GeneProduct ensembl:ENSG00000106991
TGFBR3 GeneProduct ensembl:ENSG00000069702
TGFBR1 GeneProduct ensembl:ENSG00000106799
SMAD2 GeneProduct ensembl:ENSG00000175387
SMAD3 GeneProduct ensembl:ENSG00000166949
AGTR1 GeneProduct ensembl:ENSG00000144891
SERPINE1 GeneProduct ensembl:ENSG00000106366
FBN2 GeneProduct ensembl:ENSG00000138829
FBN3 GeneProduct ensembl:ENSG00000142449
LTBP2 GeneProduct ensembl:ENSG00000119681
FLNA GeneProduct ensembl:ENSG00000196924
SMAD2 GeneProduct ensembl:ENSG00000175387
SMAD3 GeneProduct ensembl:ENSG00000166949


  1. Doetschman T, Barnett JV, Runyan RB, Camenisch TD, Heimark RL, Granzier HL, et al. Transforming growth factor beta signaling in adult cardiovascular diseases and repair. Cell Tissue Res. 2012 Jan;347(1):203–23. PubMed Europe PMC Scholia