Vascular effects of cardiotrophin-1: a role in hypertension?

Abstract

AIMS:

To investigate cardiotrophin-1 (CT-1) effects and regulation in vascular smooth muscle cells (VSMCs) in vitro and in aortic tunica media ex vivo in normotensive Wistar rats and spontaneously hypertensive rats (SHRs).

METHODS AND RESULTS:

CT-1 expression was quantified by real-time reverse-transcription PCR and western blotting. CT-1-activated intracellular pathways were assessed by western bloting analysis. Proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ki67 immunodetection, and cell hypertrophy by planimetry. Extracellular matrix components were quantified by real-time reverse-transcription PCR and western blot, and metalloproteinases activities by zymography. VSMCs from Wistar rats and SHRs expressed spontaneously CT-1 at the mRNA and the protein level, with a two-fold more increase in SHRs. CT-1 phosphorylated p42/44 mitogen-activated protein kinase, p38 mitogen-activated protein kinase, Akt and Stat-3 in both strains. CT-1 stimulated VSMCs proliferation and hypertrophy in both strains, with an enhanced stimulation in SHRs. CT-1 increased the secretion of collagen type I and fibronectin in VSMCs and aortic tunica media of Wistar rats and SHRs, with greater magnitude in SHRs. In SHRs VSMCs in vitro and ex vivo, CT-1 increased the secretion of collagen type III and elastin and the expression of tissue inhibitors of metalloproteinases, without altering metalloproteinase activity. These effects were blocked by CT-1 receptor antibodies. Aldosterone treatment increased CT-1 expression in VSMCs and aortic tunica media from both strains, with a greater magnitude in SHRs.

CONCLUSION:

CT-1 induces VSMCs proliferation, hypertrophy and extracellular matrix production, and is upregulated in hypertension and by aldosterone. CT-1 may represent a new target of vascular wall remodeling in hypertension.

• Authors: Natalia Lopez-Andres, Maria A Fortuno, Javier Diez, Faiez Zannad, Patrick Lacolley, Patrick Rossignol
• Journal: Journal of hypertension (J Hypertens) Vol. 28 Issue 6 Pg. 1261-72 (Jun 2010) ISSN: 1473-5598 [Electronic] England
• PMID: 20216087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• cardiotrophin 1

Topics

• Animals
• Blotting, Western
• Cell Proliferation
• Cells, Cultured
• Cytokines (physiology)
• Hypertension (physiopathology)
• Muscle, Smooth, Vascular (metabolism, pathology)
• Rats
• Rats, Inbred SHR
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction