The Use of Human Vascular Tissue Microarrays for Measurement of Advanced Glycation End Products

Marc K. Halushka ^1*, Elizabeth Selvin ¹, Jie Lu ¹, Anne M. Macgregor ¹ and Toby C. Cornish ¹

¹ Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, Maryland (MKH,JL,AMM,TCC), and Departments of Epidemiology and Medicine, Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins University School of Medicine, Baltimore, Maryland (ES)

^* To whom correspondence should be addressed. E-mail: mhalush1{at}jhmi.edu.

Submitted on November 20, 2008
Accepted on 27 January 2009

	Abstract

Advanced glycation end products (AGEs) are present in the vasculature and associate with vascular disease. We determined levels of AGEs in 8 distinct adult vascular tissues using tissue microarray (TMA) technology and associated these levels with clinical characteristics. Medium-to-large caliber blood vessels were harvested from 100 adult autopsies to create 17 TMAs. AGE levels were evaluated by immunohistochemistry (IHC) using a polyclonal anti-AGE antibody on over 700 unique blood vessels. Slides were digitally scanned and quantitative analysis was performed using a color deconvolution image analysis technique. Medial AGE staining was strongly correlated between all 8 blood vessels. In the media, AGE staining levels were significantly higher at older ages (p = 0.009), in Caucasian subjects (p < 0.001) and with longer post mortem interval (PMI) (p < 0.0001). These associations remained significant after simultaneous adjustment for age, race/ethnicity, PMI and diabetes status. Diabetes was associated with elevated AGE levels, but only after adjustment for confounding by clinical variables including race/ethnicity, hypertension and kidney function. This extensive vascular study demonstrates that AGE accumulation in the macrovasculature is a global process affecting atherosclerosis-prone and resistant vessels. It also suggests ethnicity has a previously undescribed role in vascular tissue AGE levels. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

Key Words: advanced glycation end products, blood vessels, immunohistochemistry, diabetes

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