ELECTRODE CUFF-INDUCED CHANGES IN DNA AND PDGF GENE-EXPRESSION IN THERAT CAROTID-ARTERY

Low current (0.25, 3 mA) stimulation through a miniature electrode cuf f encased around the carotid artery of the rat was used to induce inti mal hyperplasia, an important feature of the atherosclerotic plaque an d a phenomenon limiting the long term success of angioplasty. Compared to contralateral unstimulated arteries, 11-14 days of daily transmura l stimulation of cuffed arteries (20 min period) significantly increas ed the amount of extracted DNA (diphenylamine colorimetric assay). Low current (0.25 mA) was as effective as 3 mA in producing an increase i n extractable DNA. The cuff alone without applied current also stimula ted an increase in DNA content but to a smaller degree than in arterie s receiving current. Infusion of a calcium channel antagonist, diltiaz em, at a dose which achieved therapeutic drug levels, significantly re duced the amount of electrode cuff-induced DNA content but had no effe ct on the increase in DNA induced by the presence of the cuff without applied current. Gene expression of PDGF-A chain, PDGF-B chain and PDG F-beta receptor (betar) (Northern analysis of extracted carotid RNA) i ncreased within 4 h after electrical stimulation with 3 mA. Lower curr ent (0.25 mA) and the presence of the cuff also enhanced PDGF gene exp ression but with a delayed onset of several days. The pattern of gene expression for PDGF ligands and betar during the 11-14 days of stimula tion differed, but each remained above contralateral control levels. I t is concluded that the continued coexpression of PDGF and one of its receptors may contribute to induced hyperplastic changes.