Correlation of C4ST-1 and ChGn-2 expression with chondroitin sulfate chain elongation in atherosclerosis

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• 作者：Vita Yanti Anggraeni^a ; Noriaki Emoto^a ; ^b ; ^{emoto@med.kobe-u.ac.jp} ; Keiko Yagi^b ; Dyah Samti Mayasari^a ; Kazuhiko Nakayama^b ; Tomomi Izumikawa^c ; Hiroshi Kitagawa^c ; Ken-ichi Hirata^a
• 关键词：Atherosclerosis ; Proteoglycans ; Glycosaminoglycans ; Chondroitin sulfate ; Chondroitin 4-O-sulfotransferase-1 ; Chondroitin N-acetylgalactosaminyltransferase-2
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：4 March 2011
• 年：2011
• 卷：406
• 期：1
• 页码：36-41
• 全文大小：1589 K

文摘

Subendothelial retention of lipoproteins by proteoglycans (PGs) is the initiating event in atherosclerosis. The elongation of chondroitin sulfate (CS) chains is associated with increased low-density lipoprotein (LDL) binding and progression of atherosclerosis. Recently, it has been shown that 2 Golgi enzymes, chondroitin 4-O-sulfotransferase-1 (C4ST-1) and chondroitin N-acetylgalactosaminyltransferase-2 (ChGn-2), play a critical role in CS chain elongation. However, the roles of C4ST-1 and ChGn-2 during the progression of atherosclerosis are not known. The aim of this study was to analyze the expression of C4ST-1 and ChGn-2 in atherosclerotic lesions in vivo and determine whether their expression correlated with CS chain elongation.

Low-density lipoprotein receptor knockout (LDLr KO) mice were fed a western diet for 2, 4, and 8 weeks to stimulate development of atherosclerosis. The binding of LDL and CS PG in this mouse model was confirmed by chondroitinase ABC (ChABC) digestion and apolipoprotein B (apo B) staining. Gel filtration analysis revealed that the CS chains began to elongate as early as 2 weeks after beginning a western diet and continued as the atherosclerosis progressed. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) showed that the mRNA levels of C4ST-1 and ChGn-2 increased after 8 weeks of this diet. In contrast, the mRNA levels of their homologs, C4ST-2 and ChGn-1, were unchanged. In addition, immunohistochemical analysis demonstrated that the expression of C4ST-1 and ChGn-2 appeared to have similar site-specific patterns and coincided with biglycan expression at the aortic root.

Our results suggested that C4ST-1 and ChGn-2 may be involved in the elongation of CS chains in the arterial wall during the progression of atherosclerosis. Therefore, modulating their expression and activity might be a novel therapeutic strategy for atherosclerosis.