Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-β1 transgene in the heart

Hidehiro Nakajima, Hisako O. Nakajima, Olga Salcher, Andrea S. Dittiè, Klaus Dembowsky, Shaoliang Jing, Loren Field

Research output: Contribution to journalArticle

189 Citations (Scopus)

Abstract

Increased transforming growth factor (TGF)-βv1 activity has been observed during pathologic cardiac remodeling in a variety of animal models. In an effort to establish a causal role of TGF-β1 in this process, transgenic mice with elevated levels of active myocardial TGF-β1 were generated. The cardiac-restricted α-myosin heavy chain promoter was used to target expression of a mutant TGF-β1 cDNA harboring a cysteine-to-serine substitution at amino acid residue 33. This alteration blocks covalent tethering of the TGF-β1 latent complex to the extracellular matrix, thereby rendering a large proportion (>60%) of the transgene-encoded TGF-β1 constitutively active. Although similar levels of active TGF-β1 were present in the transgenic atria and ventricles, overt fibrosis was observed only in the atria. Surprisingly, increased active TGF-β1 levels inhibited ventricular fibroblast DNA synthesis in uninjured hearts and delayed wound healing after myocardial injury. These data suggest that increased TGF-β1 activity by itself is insufficient to promote ventricular fibrosis in the adult mouse ventricle.

Original languageEnglish
Pages (from-to)571-579
Number of pages9
JournalCirculation Research
Volume86
Issue number5
StatePublished - Mar 17 2000

Fingerprint

Transforming Growth Factors
Transgenes
Fibrosis
Cardiac Myosins
Myosin Heavy Chains
Amino Acid Substitution
Wound Healing
Serine
Transgenic Mice
Extracellular Matrix
Cysteine
Animal Models
Complementary DNA
Fibroblasts
DNA
Wounds and Injuries

Keywords

  • Cardiac fibroblast proliferation
  • Collagen
  • Cytokine
  • Extracellular matrix
  • Heart failure

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Nakajima, H., Nakajima, H. O., Salcher, O., Dittiè, A. S., Dembowsky, K., Jing, S., & Field, L. (2000). Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-β1 transgene in the heart. Circulation Research, 86(5), 571-579.

Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-β1 transgene in the heart. / Nakajima, Hidehiro; Nakajima, Hisako O.; Salcher, Olga; Dittiè, Andrea S.; Dembowsky, Klaus; Jing, Shaoliang; Field, Loren.

In: Circulation Research, Vol. 86, No. 5, 17.03.2000, p. 571-579.

Research output: Contribution to journalArticle

Nakajima, H, Nakajima, HO, Salcher, O, Dittiè, AS, Dembowsky, K, Jing, S & Field, L 2000, 'Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-β1 transgene in the heart', Circulation Research, vol. 86, no. 5, pp. 571-579.
Nakajima H, Nakajima HO, Salcher O, Dittiè AS, Dembowsky K, Jing S et al. Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-β1 transgene in the heart. Circulation Research. 2000 Mar 17;86(5):571-579.
Nakajima, Hidehiro ; Nakajima, Hisako O. ; Salcher, Olga ; Dittiè, Andrea S. ; Dembowsky, Klaus ; Jing, Shaoliang ; Field, Loren. / Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-β1 transgene in the heart. In: Circulation Research. 2000 ; Vol. 86, No. 5. pp. 571-579.
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