Transient down-regulation of L-type Ca2+ channel and dystrophin expressionafter balloon injury in rat aortic cells

Objective: Migration and proliferation of arterial smooth muscle cells are critical responses during restenosis after balloon angioplasty. We investig ated the changes in the expression of Ca2+ channels and dystrophin, two det erminants of contraction, after balloon injury of rat aortas. Methods: Prol iferation and migration of aortic myocytes were triggered in vivo by the pa ssage of an inflated balloon catheter in the aortas of 12-week-old male Wis tar rats. We used the whole-cell patch clamp technique to investigate Ba2currents (I-Ba) through Ca2+ channels in single cells freshly isolated from media and neointima at various times after injury (days 2, 7, 15, 30 and 4 5). Results: No T-type Ca2+ channel current was recorded in any cell at any time. In contrast, a dihydropyridine (DHP)-sensitive L-type I(Ba)was recor ded consistently in the media of intact aorta. After aortic injury, I-Ba de creased dramatically (at days 2 and 7) but recovered over time to reach nor mal amplitude on days 30 and 45. In the neointima, I-Ba was absent on day 1 5 but also increased gradually over time as observed at days 30 and 45. The use of a specific antibody directed against the L-type Ca2+ channel alpha (1C) subunit showed, both by immunostaining and by Western blotting, no exp ression of the Ca2+ channel protein on day 15. Parallel immunodetection of dystrophin showed that this marker of the contractile phenotype of SMCs was also not detectable at this stage in neointimal cells. Both proteins were re-expressed at days 45 and 63. Balloon injury induces a transient down-reg ulation of I-Ba in arterial cells. Conclusions: Cell dedifferentiation and proliferation in vivo abolish the expression of L-type Ca2+ channels and dy strophin in neointimal cells. These changes may be critical in the regulati on of Ca2+ homeostasis and, thereby, contraction of the arterial SMCs durin g restenosis following angioplasty. (C) 2001 Elsevier Science B.V. All righ ts reserved.