Photochemically Induced Endothelial Injury

Abstract

Thrombosis and intimal hyperplasia occur in the development of restenosis after coronary angioplasty or the progression of atherosclerosis. The development and use of animal models are thus important for understanding the mechanisms involved in thrombus formation and intimal thickening and for evaluating potential therapies. Photochemically induced thrombosis and neointima formation following endothelial injury are initiated by the reactions between a photosensitizer, rose bengal, and green light (wavelength, 540 nm). The basic mechanism for endothelial injury in this model is that the photoexcited dye produces a singlet molecular oxygen by “photodynamic type II” energy transfer to molecular oxygen. This highly reactive oxygen species may react with structural proteins and lipids in the cell membrane to initiate direct peroxidation reactions leading to endothelial membrane damage, thus providing the initial stimulus for platelet thrombus formation, followed by intimal hyperplasia. The models of such vascular diseases created in the mouse are valuable especially since a variety of transgenic or gene knockout mice is now available for identifying factors involved in the development of thrombosis and intimal hyperplasia.