Itakura Yoko, Hasegawa Yasuko, Kikkawa Yurika, Murakami Yuina, Sugiura Kosuke, Nagai-Okatani Chiaki, Sasaki Norihiko, Umemura Mariko, Takahashi Yuji, Kimura Tohru, Kuno Atsushi, Ishiwata Toshiyuki, Toyoda Masashi
Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
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.
Regen Ther. 2023 Jan 7;22:68-78. doi: 10.1016/j.reth.2022.12.009. eCollection 2023 Mar.
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.
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.
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 lectin-IB4 in different regions of the left ventricle suggests spatiotemporal changes in the number of microvessels.
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.
心力衰竭由多种因素引起,导致潜在的致病机制难以确定。由于心血管疾病往往会随着时间的推移而恶化,早期诊断是治疗的关键。此外,了解与衰老相关的心脏质性变化(目前关于衰老对心血管疾病直接影响的信息有限)对于治疗和诊断也很有用。为了填补这些研究空白,我们研究的重点是检测心脏随时间推移而发生的结构和功能分子变化,重点关注聚糖,聚糖可反映细胞的类型和状态。
我们使用基于凝集素 - 聚糖相互作用的技术——倏逝场荧光辅助凝集素微阵列和凝集素染色,研究正常小鼠心脏组织中的聚糖定位及其在衰老过程中的变化。
左心室的聚糖谱在腔侧(内侧)和壁侧(外侧)区域之间存在差异。内侧区域的特征是存在唾液酸残基。此外,在内侧区域,在较年轻的年龄就观察到了聚糖谱的年龄相关变化。左心室不同区域中用凝集素 - IB4染色的α - 半乳糖水平的年龄相关下降差异表明微血管数量存在时空变化。
聚糖谱保留了多种聚糖结构,由许多细胞群体支持,并维持心脏功能。随着进一步研究,聚糖定位和变化有可能被开发为心力衰竭迹象的标志物。