BACKGROUND: Angioplasty stimulates proliferation and migration of vascular smooth muscle cells (VSMC), leading to neointimal thickening and @entity1094 . In a @entity35 model of @entity130 ( @entity130 ), we investigated whether alterations in expression of @entity141 -activated K+ channels (KCa) contribute to intimal @entity1373 and @entity1094 . METHODS AND RESULTS: Function and expression of KCa in mature medial and neointimal VSMC were characterized in situ by combined single-cell RT-PCR and patch-clamp analysis. Mature medial VSMC exclusively expressed large-conductance KCa ( @entity9476 ) channels. Two weeks after @entity130 , expression of @entity9476 was significantly reduced in neointimal VSMC, whereas expression of intermediate-conductance KCa (IKCa1) channels was upregulated. In the aortic VSMC cell line, A7r5 epidermal growth factor (EGF) induced IKCa1 upregulation and EGF-stimulated proliferation was suppressed by the selective IKCa1 blocker @entity45495 . Daily in vivo administration of @entity45495 to @entity35 significantly reduced intimal @entity1373 by approximately 40% at 1, 2, and 6 weeks after @entity130 . Two weeks of treatment with the related compound @entity1449 was equally effective. Reduction of intimal @entity1373 was accompanied by decreased neointimal cell content, with no change in the rate of apoptosis or collagen content. CONCLUSIONS: The switch toward IKCa1 expression may promote excessive neointimal VSMC proliferation. Blockade of IKCa1 could therefore represent a new therapeutic strategy to prevent @entity256 after angioplasty.

Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for XXXX .

@entity1449 :: ('MESH:D003022', 'Chemical') :: ['clotrimazole'] @entity1094 :: ('MESH:D006083', 'Disease') :: ['vascular restenosis'] @entity9476 :: ('83731(Tax:10116)', 'Gene') :: ['BKCa'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity1373 :: ('MESH:D006965', 'Disease') :: ['hyperplasia'] @entity45495 :: ('MESH:C411671', 'Chemical') :: ['TRAM-34'] @entity256 :: ('MESH:D023903', 'Disease') :: ['restenosis'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity130 :: ('MESH:D014947', 'Disease') :: ['BCI', 'balloon catheter injury']
@entity256 :: (MESH:D023903,Disease) :: ['restenosis']
