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Synchrotron infrared imaging of advanced glycation endproducts (AGEs) in cardiac tissue from mice fed high glycemic diets

Article type: Research Article

Authors: Birarda, Giovanni | Holman, Elizabeth A. | Fu, Shang | Weikel, Karen; | Hu, Ping | Blankenberg, Francis G. | Holman, Hoi-Ying; | Taylor, Allen

Affiliations: Berkeley Synchrotron Infrared Structural Biology Program, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA, USA | Department of Radiology and Pediatrics/Molecular Imaging Program at Stanford, Stanford, CA, USA | Laboratory for Nutrition and Vision Research, Jean Mayer USDA HNRCA at Tufts University, Tufts University, Boston, MA, USA | Boston Medical Center, Boston University School of Medicine, Boston, MA, USA

Note: [] Corresponding author: Hoi-Ying Holman, Berkeley Synchrotron Infrared Structural Biology (BSISB) Program, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA, USA. E-mail: [email protected]

Keywords: AGE, CVD, diabetes, fluorescence, glycemia, glycation, infrared, N•-(carboxymethyl)lysine, PAGE, pentosidine, RAGE, sugar

DOI: 10.3233/BSI-130057

Journal: Biomedical Spectroscopy and Imaging, vol. 2, no. 4, pp. 301-315, 2013

Published: 2013
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Abstract

Recent research findings correlate an increased risk for dieases such as diabetes, macular degeneration and cardiovascular disease (CVD) with diets that rapidly raise the blood sugar levels; these diets are known as high glycemic index (GI) diets which include white breads, sodas and sweet deserts. Lower glycemia diets are usually rich in fruits, non-starchy vegetables and whole grain products. The goal of our study was to compare and contrast the effects of a low vs. high glycemic diet using the biochemical composition and microstructure of the heart. The improved spatial resolution and signal-to-noise for SR-FTIR obtained through the coupling of the bright synchrotron infrared photon source to an infrared spectral microscope enabled the molecular-level observation of diet-related changes within unfixed fresh frozen histologic sections of mouse cardiac tissue. High and low glycemic index (GI) diets were started at the age of five-months and continued for one year, with the diets only differing in their starch distribution (high GI diet = 100% amylopectin versus low GI diet = 30% amylopectin/70% amylose). Serial cryosections of cardiac tissue for SR-FTIR imaging alternated with adjacent hematoxylin and eosin (H&E) stained sections allowed not only fine-scale chemical analyses of glycogen and glycolipid accumulation along a vein as well as protein glycation hotspots co-localizing with collagen cold spots but also the tracking of morphological differences occurring in tandem with these chemical changes. As a result of the bright synchrotron infrared photon source coupling, we were able to provide significant molecular evidence for a positive correlation between protein glycation and collagen degradation in our mouse model. Our results bring a new insight not only to the effects of long-term GI dietary practices of the public but also to the molecular and chemical foundation behind the cardiovascular disease pathogenesis commonly seen in diabetic patients.

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