Effects of AGE/RAGE on Monocytes in Arteriogenesis

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DESCRIPTION (provided by applicant): By the year 2010 it is projected that the total number of people worldwide with diabetes will reach 221 million, with as many as 80% of these patients succumb to complications closely associated with vascular disease. The capacity to form collateral blood vessels is vital to compensate for tissue ischemia resulting from vascular occlusive disease, and this ability is significantly decreased in the diabetic patient. The formation of advanced glycation endproducts (AGEs) occurs in the normal process of aging, but is enhanced in the chronic hyperglycemic state of diabetes. AGEs have been implicated in the development of diabetic vascular complications. Monocytes play an important role in the arteriogenic process and during collateral growth and are known to be affected by AGEs. The specific aims of this project are to examine the effects of monocyte expression of the receptor for AGE in diabetic mice on arteriogenesis via hind-limb ischemia appraised by microcomputed tomography, and to examine the functional consequences of AGE/RAGE stimulation on the inherent motility of monocytes derived from the above model.