Inhibition of Ca 2+ ‐calcineurin/Nuclear Factor of Activated T‐cells (NFAT) signaling reduces the expression of TRPC1 but not TRPC6 in vascular smooth muscle

Occlusive vascular disease is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. We have recently shown that TRPC1 and TRPC6, mammalian homologs of Drosophila transient receptor potential, are both upregulated Ca 2+ ‐channels in the adaptive injury response of blood vessels. So far, the factors controlling TRPC expression are largely unknown. In this study, we investigate the involvement of the NFAT signaling pathway in the regulation of TRPC expression. Western blot analysis revealed that NFAT inhibition during organ culture of intact mouse aorta for 3 days yielded decreased TRPC1 expression. This effect was more pronounced in the abdominal than in the thoracic aorta. Accordingly, NFAT activity, as assessed in arteries from NFAT‐luciferase transgenic mice, is lower in the thoracic regions of the aorta. TRPC6 expression was not affected by NFAT inhibition. Several NFAT‐dependent binding elements were identified in the promoter region of TRPC1 but none in the promoter region of TRPC6. We also show that STIM1, a proposed key regulator of TRPC1 channel activity, is expressed in native arteries and modulated during organ culture of native vessels.