Spatiotemporal changes of tissue glycans depending on localization in cardiac aging

Yoko Itakura; Yasuko Hasegawa; Yurika Kikkawa; Yuina Murakami; Kosuke Sugiura; Chiaki Nagai-Okatani; Norihiko Sasaki; Mariko Umemura; Yuji Takahashi; Tohru Kimura; Atsushi Kuno; Toshiyuki Ishiwata; Masashi Toyoda

doi:10.1016/j.reth.2022.12.009

Spatiotemporal changes of tissue glycans depending on localization in cardiac aging

Regen Ther. 2023 Jan 7:22:68-78. doi: 10.1016/j.reth.2022.12.009. eCollection 2023 Mar.

Authors

Yoko Itakura¹, Yasuko Hasegawa², Yurika Kikkawa^{1

3}, Yuina Murakami^{1

4}, Kosuke Sugiura^{1

3}, Chiaki Nagai-Okatani⁵, Norihiko Sasaki¹, Mariko Umemura⁴, Yuji Takahashi⁴, Tohru Kimura³, Atsushi Kuno⁵, Toshiyuki Ishiwata², Masashi Toyoda¹

Affiliations

¹ Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
² Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
³ Laboratory of Stem Cell Biology, Department of Biosciences, Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0373, Japan.
⁴ Laboratory of Environmental Molecular Physiology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
⁵ Cellular and Molecular Biotechnology Research Institute, National Institutes of Advanced Industrial Science and Technology, 5 Central, Tsukuba, 1-1-1 Higashi, Tsukuba-city, Ibaraki 305-8565, Japan.

Abstract

Heart failure is caused by various factors, making the underlying pathogenic mechanisms difficult to identify. Since cardiovascular disease tends to worsen over time, early diagnosis is key for treatment. In addition, understanding the qualitative changes in the heart associated with aging, where information on the direct influences of aging on cardiovascular disease is limited, would also be useful for treatment and diagnosis. To fill these research gaps, the focus of our study was to detect the structural and functional molecular changes associated with the heart over time, with a focus on glycans, which reflect the type and state of cells.

Methods: We investigated glycan localization in the cardiac tissue of normal mice and their alterations during aging, using evanescent-field fluorescence-assisted lectin microarray, a technique based on lectin-glycan interaction, and lectin staining.

Results: The glycan profiles in the left ventricle showed differences between the luminal side (medial) and wall side (lateral) regions. The medial region was characterized by the presence of sialic acid residues. Moreover, age-related changes in glycan profiles were observed at a younger age in the medial region. The difference in the age-related decrease in the level of α-galactose stained with Griffonia simplicifolia lectin-IB4 in different regions of the left ventricle suggests spatiotemporal changes in the number of microvessels.

Conclusions: The glycan profile, which retains diverse glycan structures, is supported by many cell populations, and maintains cardiac function. With further research, glycan localization and changes have the potential to be developed as a marker of the signs of heart failure.

Keywords: ACG, Agrocybe cylindracea galectin; Aging; BPL, Bauhinia purpurea alba lectin; Calsepa, Calystegia sepium agglutinin; Cardiac tissue; ConA, Canavalia ensiformis lectin; DAPI, 4′,6-diamidino-2-phenylindole; DBA, Dolichos biflorus agglutinin; ECA, Erythrina cristagalli agglutinin; ECM, extracellular matrices; EMT, endothelial-to-mesenchymal transition; FITC, fluorescein isothiocyanate; GSL-I, Griffonia simplicifolia lectin I; Gal, galactose; GalNAc, N-acetylgalactosamine; GlcNAc, N-acetylglucosamine; Glycan profile; HE, hematoxylin-eosin; LEL, Lycopersicon esculentum lectin; LTL, Lotus tetragonolobus lectin; Lectin microarray; MAH, Maackia amurensis hemagglutinin; MAL-I, Maackia amurensis lectin I; Man, mannose; Microvessels; NPA, Narcissus pseudonarcissus agglutinin; PBS, phosphate-buffered saline; PCA, principal component analysis; PHA-L, Phaseolus vulgaris leucoagglutinin; PNA, Arachis hypogaea agglutinin; RCA120, Ricinus communis agglutinin I; SBA, Glycine max agglutinin; SNA, Sambucus nigra agglutinin; SSA, Sambucus sieboldiana agglutinin; STL, Solanum tuberosum lectin; TJA-I, Trichosanthes japonica agglutinin I; UDA, Urtica dioica; VVA, Vicia villosa agglutinin; WFA, Wisteria floribunda agglutinin; WGA, Triticum vulgaris agglutinin (wheat germ agglutinin); α-SMA, alpha smooth muscle actin.