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J Am Heart Assoc. 2014 Mar 10;3(2):e000626. doi: 10.1161/JAHA.113.000626.

Arterial wall stress controls NFAT5 activity in vascular smooth muscle cells.

Author information

1
Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.

Abstract

BACKGROUND:

Nuclear factor of activated T-cells 5 (NFAT5) has recently been described to control the phenotype of vascular smooth muscle cells (VSMCs). Although an increase in wall stress or stretch (eg, elicited by hypertension) is a prototypic determinant of VSMC activation, the impact of this biomechanical force on the activity of NFAT5 is unknown. This study intended to reveal the function of NFAT5 and to explore potential signal transduction pathways leading to its activation in stretch-stimulated VSMCs.

METHODS AND RESULTS:

Human arterial VSMCs were exposed to biomechanical stretch and subjected to immunofluorescence and protein-biochemical analyses. Stretch promoted the translocation of NFAT5 to the nucleus within 24 hours. While the protein abundance of NFAT5 was regulated through activation of c-Jun N-terminal kinase under these conditions, its translocation required prior activation of palmitoyltransferases. DNA microarray and ChiP analyses identified the matrix molecule tenascin-C as a prominent transcriptional target of NFAT5 under these conditions that stimulates migration of VSMCs. Analyses of isolated mouse femoral arteries exposed to hypertensive perfusion conditions verified that NFAT5 translocation to the nucleus is followed by an increase in tenascin-C abundance in the vessel wall.

CONCLUSIONS:

Collectively, our data suggest that biomechanical stretch is sufficient to activate NFAT5 both in native and cultured VSMCs where it regulates the expression of tenascin-C. This may contribute to an improved migratory activity of VSMCs and thus promote maladaptive vascular remodeling processes such as hypertension-induced arterial stiffening.

KEYWORDS:

NFAT5; hypertension; tenascin‐C; vascular smooth muscle cells; wall stress

PMID:
24614757
PMCID:
PMC4187483
DOI:
10.1161/JAHA.113.000626
[Indexed for MEDLINE]
Free PMC Article

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