Hypothesized pathways in pathogenesis of cardiovascular disease (WP3668)
Homo sapiens
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 [https://assays.cancer.gov/available_assays?wp_id=WP3668 CPTAC Assay Portal]
Authors
AAR&Co , Jonathan Mélius , Kristina Hanspers , Andika Tan , Friederike Ehrhart , Eric Weitz , and Egon WillighagenActivity
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Cited In
- Understanding signaling and metabolic paths using semantified and harmonized information about biological interactions (2022).
- Comprehensive Statistical and Bioinformatics Analysis in the Deciphering of Putative Mechanisms by Which Lipid-Associated GWAS Loci Contribute to Coronary Artery Disease (2022).
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Organisms
Homo sapiensCommunities
DiseasesAnnotations
Pathway Ontology
cardiovascular system disease pathway cardiomyopathy pathway disease pathwayDisease Ontology
Kawasaki disease heart valve disease cardiovascular system disease hypertension atherosclerosis aortic aneurysm cardiomyopathyCell Type Ontology
endocardial cellLabel | Type | Compact URI | Comment |
---|---|---|---|
MAPK3 | GeneProduct | ensembl:ENSG00000102882 | |
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 | Firbrillins Not Specified |
CTGF | GeneProduct | ensembl:ENSG00000118523 | |
NR2C2 | GeneProduct | ensembl:ENSG00000177463 | |
LTBP1 | GeneProduct | ensembl:ENSG00000049323 | LTBP Not Specified |
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 | Identifier Not Found |
SERPINE1 | GeneProduct | ensembl:ENSG00000106366 | |
FBN2 | GeneProduct | ensembl:ENSG00000138829 | Firbrillins Not Specified |
FBN3 | GeneProduct | ensembl:ENSG00000142449 | Firbrillins Not Specified |
LTBP2 | GeneProduct | ensembl:ENSG00000119681 | LTBP Not Specified |
FLNA | GeneProduct | ensembl:ENSG00000196924 |
References
- Transforming growth factor beta signaling in adult cardiovascular diseases and repair. Doetschman T, Barnett JV, Runyan RB, Camenisch TD, Heimark RL, Granzier HL, et al. Cell Tissue Res. 2012 Jan;347(1):203–23. PubMed Europe PMC Scholia