Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration

Adhikara, Imam Manggalya; Yagi, Kazuichi; Mayasari, Dyah Samti; Ikeda, Koji; Kitagawa, Hiroshi; Miyata, Okiko; Igarashi, Michihiro; Hatakeyama, Kinta; Asada, Yujiro; Hirata, Ken‐ichi; Emoto, Noriaki

doi:10.1016/j.bbrc.2018.12.068

Cited by 7 publications

(3 citation statements)

References 27 publications

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“…Formalin fixed, parrafin‐embedded heart sections were stained with Masson trichrome 28 and Alcian Blue 18 as described previously. Fibrosis area in the heart was quantified using Image J software.…”

Section: Methodsmentioning

confidence: 99%

“… 17 Deletion of ChGn‐2 was previously shown to reduce and shorten the length of CS chain in mouse tissues. 18 , 19 , 20 This reduction of CS‐GAGs chain showed beneficial effects in the prevention of atherosclerosis by reducing the oxidized LDL accumulation in the intima and on the macrophage surface. 18 , 19 On the other hand, another perspective was reported that CS administration attenuated atherosclerosis in ApoE‐deficient mice potentially by inhibiting foam cell formation of macrophages.…”

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confidence: 96%

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ChGn‐2 Plays a Cardioprotective Role in Heart Failure Caused by Acute Pressure Overload

Haryono

Ikeda

Nugroho

et al. 2022

JAHA

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Background Cardiac extracellular matrix is critically involved in cardiac homeostasis, and accumulation of chondroitin sulfate glycosaminoglycans (CS‐GAGs) was previously shown to exacerbate heart failure by augmenting inflammation and fibrosis at the chronic phase. However, the mechanism by which CS‐GAGs affect cardiac functions remains unclear, especially at the acute phase. Methods and Results We explored a role of CS‐GAG in heart failure using mice with target deletion of ChGn‐2 (chondroitin sulfate N‐acetylgalactosaminyltransferase‐2) that elongates CS chains of glycosaminoglycans. Heart failure was induced by transverse aortic constriction in mice. The role of CS‐GAG derived from cardiac fibroblasts in cardiomyocyte death was analyzed. Cardiac fibroblasts were subjected to cyclic mechanical stretch that mimics increased workload in the heart. Significant CS‐GAGs accumulation was detected in the heart of wild‐type mice after transverse aortic constriction, which was substantially reduced in ChGn‐2 ‐/‐ mice. Loss of ChGn‐2 deteriorated the cardiac dysfunction caused by pressure overload, accompanied by augmented cardiac hypertrophy and increased cardiomyocyte apoptosis. Cyclic mechanical stretch increased ChGn‐2 expression and enhanced glycosaminoglycan production in cardiac fibroblasts. Conditioned medium derived from the stretched cardiac fibroblasts showed cardioprotective effects, which was abolished by CS‐GAGs degradation. We found that CS‐GAGs elicits cardioprotective effects via dual pathway; direct pathway through interaction with CD44, and indirect pathway through binding to and activating insulin‐like growth factor‐1. Conclusions Our data revealed the cardioprotective effects of CS‐GAGs; therefore, CS‐GAGs may play biphasic role in the development of heart failure; cardioprotective role at acute phase despite its possible unfavorable role in the advanced phase.

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Section: Methodsmentioning

confidence: 99%

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confidence: 96%

ChGn‐2 Plays a Cardioprotective Role in Heart Failure Caused by Acute Pressure Overload

Haryono

Ikeda

Nugroho

et al. 2022

JAHA

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“…In addition, decorin, which is a small CS/DSPG, interacts with type I collagen accumulated in atherosclerotic lesions and binds to LDL to enhance the retention of lipoproteins in the arterial wall (Pentikainen et al, 1997). There is also direct evidence that CS/DSPGs are involved in arteriosclerosis, the absence of chondroitin sulfate N-acetylgalactosaminyltransferase-2 can reduce lipoprotein retention in the early stage of atherosclerosis and reduce the migration of aortic smooth muscle cells (Adhikara et al, 2019). CSPG binds to lipoproteins mainly through its GAG chain.…”

Section: Atherosclerosismentioning

confidence: 99%

Chondroitin Sulfate/Dermatan Sulfate-Protein Interactions and Their Biological Functions in Human Diseases: Implications and Analytical Tools

Zhang

2021

Front. Cell Dev. Biol.

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Chondroitin sulfate (CS) and dermatan sulfate (DS) are linear anionic polysaccharides that are widely present on the cell surface and in the cell matrix and connective tissue. CS and DS chains are usually attached to core proteins and are present in the form of proteoglycans (PGs). They not only are important structural substances but also bind to a variety of cytokines, growth factors, cell surface receptors, adhesion molecules, enzymes and fibrillary glycoproteins to execute series of important biological functions. CS and DS exhibit variable sulfation patterns and different sequence arrangements, and their molecular weights also vary within a large range, increasing the structural complexity and diversity of CS/DS. The structure-function relationship of CS/DS PGs directly and indirectly involves them in a variety of physiological and pathological processes. Accumulating evidence suggests that CS/DS serves as an important cofactor for many cell behaviors. Understanding the molecular basis of these interactions helps to elucidate the occurrence and development of various diseases and the development of new therapeutic approaches. The present article reviews the physiological and pathological processes in which CS and DS participate through their interactions with different proteins. Moreover, classic and emerging glycosaminoglycan (GAG)-protein interaction analysis tools and their applications in CS/DS-protein characterization are also discussed.

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Lipid: Extracellular Matrix Interactions as Therapeutic Targets in the Atherosclerosis of Diabetes

Kamato

Little

2023

Contemporary Diabetes

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Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration

Cited by 7 publications

References 27 publications

ChGn‐2 Plays a Cardioprotective Role in Heart Failure Caused by Acute Pressure Overload

ChGn‐2 Plays a Cardioprotective Role in Heart Failure Caused by Acute Pressure Overload

Chondroitin Sulfate/Dermatan Sulfate-Protein Interactions and Their Biological Functions in Human Diseases: Implications and Analytical Tools

Lipid: Extracellular Matrix Interactions as Therapeutic Targets in the Atherosclerosis of Diabetes

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