This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Atherosclerosis is a progressive disease that is characterized by the accumulation of lipids, monocytes, fibrous constituents, and various other inflammatory cells in the arterial wall. These deposits form vascular lesions known as atheromatous plaques, which contain necrotic cores and are separated from the arterial intima by a fibrous cap made up of collagen and smooth muscle cells. When these plaques become vulnerable to rupture, they release the inflammatory elements of the necrotic core into the artery, causing thrombosis and obstruction of arterial blood flow. We analyzed plaque structure and development in diseased tissue samples of post-mortem human aortas through multiphoton microscopy (MPM). Specifically, we observed second-harmonic generation (SHG) signals from collagen in the fibrous cap, which is slowly degraded during plaque development. By analyzing collagen structure and degradation, different stages of vulnerable plaque growth and development can be discerned. This study provides a useful method for diagnosing atherosclerosis at even its earliest stages.
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