PhotoPoint Photodynamic Therapy Promotes Stabilization of Atherosclerotic Plaques and Inhibits Plaque Progression

Abstract

The purpose of this study was to determine how photodynamic therapy (PDT) promotes stabilization and reduction of regional atherosclerosis. Photodynamic therapy, a combination of photosensitizer and targeted light to promote cell apoptosis, has been shown to reduce atherosclerotic plaque inflammation. Forty New Zealand White rabbits were fed with cholesterol. The iliac arteries were balloon denuded and randomized to receive either PhotoPoint PDT treatment (photosensitizer and light) (Miravant Medical Technologies, Santa Barbara, California), photosensitizer (MV0611) alone, or light alone and were then compared at 7 and 28 days. Arteries were examined for evidence of plaque volume, cell number, macrophage and smooth muscle cell (SMC) content, and plaque cell proliferation. Compared with contralateral iliac artery controls at 7 days, plaque progression was reduced by approximately 35% (p < 0.01); plaque progression was further reduced to approximately 53% (p < 0.01) by 28 days, leading to an increase in lumen patency (p < 0.05). At 7 days after PDT, percent plaque area occupied by macrophages decreased by approximately 98% (p < 0.001) and SMCs by approximately 72% (p < 0.05). At 28 days after PDT, removal of macrophages was sustained (approximately 92% decrease, p < 0.001) and plaques were repopulated with non-proliferating SMCs (approximately 220% increase, p < 0.001). There was no evidence of negative or expansive arterial remodeling, thrombosis, or aneurysm formation. Photodynamic therapy simultaneously reduces plaque inflammation and promotes repopulation of plaques with a SMC-rich stable plaque cell phenotype while reducing disease progression. These early healing responses suggest that PDT is a promising therapy for the treatment of acute coronary syndromes.