Physiological and pathological hypertrophy of the heart (WP1528)

Homo sapiens

Pathways in physiological and pathological hypertrophy of the heart. Largely based on the article from [ Wang et al, 'Signal transduction in cardiac hypertrophy--dissecting compensatory versus pathological pathways utilizing a transgenic approach.] Hypertrohpy of the heart can be a physiological compensation for exercise, but it can also be a pathological compensation for hypertension and stress. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


Maartje Levels , Susan Coort , Alex Pico , Kristina Hanspers , Friederike Ehrhart , Egon Willighagen , Andika Tan , and Eric Weitz


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Homo sapiens




Pathway Ontology

hypertrophic cardiomyopathy pathway

Cell Type Ontology

cardiac muscle cell

Disease Ontology

heart disease


Label Type Compact URI Comment
PE Metabolite hmdb:HMDB0002182
Calcium Metabolite hmdb:HMDB0000464
MKK3 GeneProduct ncbigene:5606
MYEF2 GeneProduct ncbigene:50804
MAPK14 GeneProduct ncbigene:1432
PRKCB GeneProduct ncbigene:5579
LIFR GeneProduct ncbigene:3977
JNK GeneProduct ncbigene:5599
CAMK2D GeneProduct ncbigene:817
CTF1 GeneProduct ncbigene:1489
JUN GeneProduct ncbigene:3725
PPP3CB GeneProduct ncbigene:5532
PKCE GeneProduct ncbigene:5581
RAC1 GeneProduct ncbigene:5879
EDN1 GeneProduct ncbigene:1906
FOS GeneProduct ncbigene:2353
MAPK11 GeneProduct ncbigene:5600
RHOA GeneProduct ncbigene:387
NFAT3 GeneProduct ncbigene:4776
JNK GeneProduct ncbigene:5599
PPP3CA GeneProduct ncbigene:5530
STAT3 GeneProduct ncbigene:6774
MAPK14 GeneProduct ncbigene:1432
GATA4 GeneProduct ncbigene:2626
MAPK1 GeneProduct ncbigene:5594
AGT GeneProduct ncbigene:183
IL6ST GeneProduct ncbigene:3572
CALM1 Protein ncbigene:801


  1. Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. Assembly of sarcomeric units in series VIA gp130/leukemia inhibitory factor receptor-dependent pathways. Wollert KC, Taga T, Saito M, Narazaki M, Kishimoto T, Glembotski CC, et al. J Biol Chem. 1996 Apr 19;271(16):9535–45. PubMed Europe PMC Scholia
  2. Cardiotrophin-1 and the role of gp130-dependent signaling pathways in cardiac growth and development. Wollert KC, Chien KR. J Mol Med (Berl). 1997 Jul;75(7):492–501. PubMed Europe PMC Scholia
  3. Cardiac hypertrophy induced by mitogen-activated protein kinase kinase 7, a specific activator for c-Jun NH2-terminal kinase in ventricular muscle cells. Wang Y, Su B, Sah VP, Brown JH, Han J, Chien KR. J Biol Chem. 1998 Mar 6;273(10):5423–6. PubMed Europe PMC Scholia
  4. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, et al. Cell. 1998 Apr 17;93(2):215–28. PubMed Europe PMC Scholia
  5. Calcineurin and human heart failure. Lim HW, Molkentin JD. Nat Med. 1999 Mar;5(3):246–7. PubMed Europe PMC Scholia
  6. Prevention of cardiac hypertrophy by calcineurin inhibition: hope or hype? Olson EN, Molkentin JD. Circ Res. 1999 Apr 2;84(6):623–32. PubMed Europe PMC Scholia
  7. Signaling pathways for cardiac hypertrophy and failure. Hunter JJ, Chien KR. N Engl J Med. 1999 Oct 21;341(17):1276–83. PubMed Europe PMC Scholia
  8. Signal transduction during cardiac hypertrophy: the role of G alpha q, PLC beta I, and PKC. Jalili T, Takeishi Y, Walsh RA. Cardiovasc Res. 1999 Oct;44(1):5–9. PubMed Europe PMC Scholia
  9. Small guanine nucleotide-binding proteins and myocardial hypertrophy. Clerk A, Sugden PH. Circ Res. 2000 May 26;86(10):1019–23. PubMed Europe PMC Scholia
  10. Transgenic overexpression of constitutively active protein kinase C epsilon causes concentric cardiac hypertrophy. Takeishi Y, Ping P, Bolli R, Kirkpatrick DL, Hoit BD, Walsh RA. Circ Res. 2000 Jun 23;86(12):1218–23. PubMed Europe PMC Scholia
  11. Advances in the molecular mechanisms of heart failure. MacLellan WR. Curr Opin Cardiol. 2000 May;15(3):128–35. PubMed Europe PMC Scholia
  12. Calcineurin and beyond: cardiac hypertrophic signaling. Molkentin JD. Circ Res. 2000 Oct 27;87(9):731–8. PubMed Europe PMC Scholia
  13. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. Bueno OF, De Windt LJ, Tymitz KM, Witt SA, Kimball TR, Klevitsky R, et al. EMBO J. 2000 Dec 1;19(23):6341–50. PubMed Europe PMC Scholia
  14. Signal transduction in cardiac hypertrophy--dissecting compensatory versus pathological pathways utilizing a transgenic approach. Wang Y. Curr Opin Pharmacol. 2001 Apr;1(2):134–40. PubMed Europe PMC Scholia
  15. Regulation of cardiac hypertrophy by intracellular signalling pathways. Heineke J, Molkentin JD. Nat Rev Mol Cell Biol. 2006 Aug;7(8):589–600. PubMed Europe PMC Scholia