Inducible expression of the signal transduction protein 14-3-3γ in injured arteries and stimulated human vascular smooth muscle cells

Although the 14-3-3 family of proteins have been shown to be key signal transduction proteins involved in regulation of cellular growth and proliferation, little has been reported on their expression in pathophysiological states. We hypothesized that expression of one isoform, 14-3-3γ, would also be increased in vascular proliferative diseases. We observed 14-3-3γ expression induced in human coronary artery vasculopathy (CAV) as compared with coronary arteries isolated from normal and end-stage heart failure patients. 14-3-3γ is acutely expressed in aortic medial smooth muscle cells in experimental models of arterial injury including rat cardiac allografts balloon angioplasty-injured swine coronary arteries. In each case, 14-3-3γ protein expression is induced by 3 days and peaks at 7-10 days post-injury. Expression of this protein in cultured human vascular smooth muscle cells (VSMC) is associated with cytokine-induced VSMC activation, rather than direct injury to the VSMC themselves, and is unique among other 14-3-3 family proteins. Potential 14-3-3γ protein-protein interactions are also differentially regulated by cytokine stimulation. This study indicates that 14-3-3γ expression is induced in arterial trauma by cytokines, and suggests that this protein may play an important role in progression of vascular proliferative diseases.