PhotoPoint photodynamic therapy promotes stabilization of atherosclerotic plaques and inhibits plaque progression

PhotoPoint 光动力疗法促进动脉粥样硬化斑块稳定并抑制斑块进展

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作者:Ron Waksman, Pauline E McEwan, Travis I Moore, Rajbabu Pakala, Frank D Kolodgie, David G Hellinga, Rufus C Seabron, Steven J Rychnovsky, Jeffrey Vasek, Robert W Scott, Renu Virmani

Background

Photodynamic therapy, a combination of photosensitizer and targeted light to promote cell apoptosis, has been shown to reduce atherosclerotic plaque inflammation.

Conclusions

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.

Methods

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.

Results

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. Conclusions: 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.

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