title: Amplified pathogenic actions of angiotensin II in cysteine-rich LIM-only protein 4-negative mouse hearts.
abstract: LIM domain proteins have been identified as essential modulators of cardiac biology and pathology; however, it is unclear which role the cysteine-rich LIM-only protein (CRP)4 plays in these processes. In studying CRP4 mutant mice, we found that their hearts developed normally, but lack of CRP4 exaggerated multiple parameters of the cardiac stress response to the neurohormone angiotensin II (Ang II). Aiming to dissect the molecular details, we found a link between CRP4 and the cardioprotective cGMP pathway, as well as a multiprotein complex comprising well-known hypertrophy-associated factors.Significant enrichment of the cysteine-rich intestinal protein (CRIP)1 in murine hearts lacking CRP4, as well as severe cardiac defects and premature death of CRIP1 and CRP4 morphant zebrafish embryos, further support the notion that depleting CRP4 is incompatible with a proper cardiac development and function. Together, amplified Ang II signaling identified CRP4 as a novel antiremodeling factor regulated, at least to some extent, by cardiac cGMP.-Straubinger, J., Boldt, K., Kuret, A., Deng, L., Krattenmacher, D., Bork, N., Desch, M., Feil, R., Feil, S., Nemer, M., Ueffing, M., Ruth, P., Just, S., Lukowski, R. Amplified pathogenic actions of angiotensin II in cysteine-rich LIM-only protein 4 negative mouse hearts.
authors.affiliation: Department of Pharmacology, Toxicology, and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, Tübingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Straubinger
authors.affiliation: Institute for Ophthalmic Research, Molecular Biology of Retinal Degenerations and Medical Proteome Center, University of Tübingen, Tübingen, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Boldt
authors.affiliation: Department of Pharmacology, Toxicology, and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, Tübingen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Kuret
authors.affiliation: Department of Pharmacology, Toxicology, and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, Tübingen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Deng
authors.affiliation: Molecular Cardiology, Department of Internal Medicine II, University of Ulm, Ulm, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Krattenmacher
authors.affiliation: Department of Pharmacology, Toxicology, and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, Tübingen, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Bork
authors.affiliation: Department of Pharmacology, Toxicology, and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Desch
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany; and.
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany; and.
authors.forename: Susanne
authors.initials: S
authors.lastname: Feil
authors.affiliation: Laboratory of Cardiac Development and Differentiation, Department of Biochemistry, Immunology, and Microbiology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Mona
authors.initials: M
authors.lastname: Nemer
authors.affiliation: Institute for Ophthalmic Research, Molecular Biology of Retinal Degenerations and Medical Proteome Center, University of Tübingen, Tübingen, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
authors.affiliation: Department of Pharmacology, Toxicology, and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.affiliation: Molecular Cardiology, Department of Internal Medicine II, University of Ulm, Ulm, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Just
authors.affiliation: Department of Pharmacology, Toxicology, and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, Tübingen, Germany; robert.lukowski@uni-tuebingen.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Lukowski
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000254:growth & development; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D015027:Zebrafish; D023084:alpha-Defensins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C489507:Crip1 protein, mouse; D060588:LIM Domain Proteins; D023084:alpha-Defensins; C401847:cryptdin 4, mouse; D000804:Angiotensin II; D006152:Cyclic GMP
keywords: BNP; CRP4; Crip1; cGMP; cardiac hypertrophy