PREVENTION OF LATE LUMEN LOSS AFTER CORONARY ANGIOPLASTY BY PHOTODYNAMIC THERAPY - ROLE OF ACTIVATED NEUTROPHILS

Restenosis after coronary angioplasty arises from fibrocellular intima l hyperplasia and possibly failure of the artery to enlarge adequately . Which mechanisms underlie this process is only partly understood. No drugs have been clinically effective in reducing the incidence of res tenosis. Since recently, photodynamic therapy (PDT) is being investiga ted as a possible treatment for intimal hyperplasia. PDT involves the systemic administration of a light-excitable photosensitizer that is t aken up rather preferentially by rapidly proliferating cells. During l aser irradiation light energy is transferred from the photosensitizer to oxygen generating the highly reactive singlet oxygen. This potent o xidizer can cause severe cellular damage. After PDT of a balloon-injur ed artery from the rat and rabbit the media remained acellular for sev eral weeks to months, and intimal hyperplasia did not occur. The endot helial lining regenerated by two weeks, but why smooth muscle cells di d not repopulated the media is not known. Neutrophils seem to play an important role in the prevention of restenosis after coronary angiopla sty, since the activation status of this type of phagocyte is directly related to vessel diameter at late follow-up. Furthermore, it has bee n observed that neutrophils adhere to the microvascular wall upon PDT in vivo. In vitro findings suggest that the increased neutrophil adher ence was not dependent on a decreased release of the anti-adhesive fac tors NO and prostacyclin by the PDT-treated endothelial cells. Further more, PDT did not stimulate the expression of P-selectin by the endoth elial cells, one of the adhesion receptors for neutrophils. The endoth elial cells only retract upon PDT allowing the adherence of neutrophil s by their beta(2)-integrin adhesion receptors to the subendothelial m atrix. On the basis of these findings, we presume that the successful prevention of intimal hyperplasia by PDT partly depends on the presenc e of the neutrophil at the site of the lesion.