Electrode cuff-induced changes in DNA and PDGF gene expression in the rat carotid artery

Low current (0.25, 3 mA) stimulation through a miniature electrode cuff encased around the carotid artery of the rat was used to induce intimal hyperplasia, an important feature of the atherosclerotic plaque and a phenomenon limiting the long term success of angioplasty. Compared to contralateral unstimulated arteries, 11-14 days of daily transmural stimulation of cuffed arteries (20 min period) significantly increased the amount of extracted DNA (diphenylamine colorimetric assay). Low current (0.25 mA) was as effective as 3 mA in producing an increase in extractable DNA. The cuff alone without applied current also stimulated an increase in DNA content but to a smaller degree than in arteries receiving current. Infusion of a calcium channel antagonist, diltiazem, at a dose which achieved therapeutic drug levels, significantly reduced the amount of electrode cuff-induced DNA content but had no effect 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 PDGF-beta receptor (beta r) (Northern analysis of extracted carotid RNA) increased within 4 h after electrical stimulation with 3 mA. Lower current (0.25 mA) and the presence of the cuff also enhanced PDGF gene expression but with a delayed onset of several days. The pattern of gene expression for PDGF ligands and beta r during the 11-14 days of stimulation differed, but each remained above contralateral control levels. It is concluded that the continued coexpression of PDGF and one of its receptors may contribute to induced hyperplastic changes.