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

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

doi:10.3233/BSI-130057

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

Biomed Spectrosc Imaging. 2013;2(4):301-315. doi: 10.3233/BSI-130057.

Authors

Giovanni Birarda¹, Elizabeth A Holman², Shang Fu³, Karen Weikel⁴, Ping Hu¹, Francis G Blankenberg², Hoi-Ying Holman¹, Allen Taylor³

Affiliations

¹ Berkeley Synchrotron Infrared Structural Biology Program, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA, USA.
² Department of Radiology and Pediatrics/Molecular Imaging Program at Stanford, Stanford, CA, USA.
³ Laboratory for Nutrition and Vision Research, Jean Mayer USDA HNRCA at Tufts University, Tufts University, Boston, MA, USA.
⁴ 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.

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.

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

Abstract

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