Elastin Insufficiency Predisposes Mice to Impaired Glucose Metabolism

DeMarsilis, Antea J.; Walji, Tezin A.; Maedeker, Justine A.; Stoka, Kellie V.; Kozel, Beth A.; Mecham, Robert P.; Wagenseil, Jessica E.; Craft, Clarissa S.

doi:10.4172/1747-0862.1000129

Cited by 8 publications

(7 citation statements)

References 29 publications

(37 reference statements)

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“…2D) significantly. Previously, several studies have demonstrated that elastic fiber integrity is an important factor for glucose and lipid homeostasis (8,15). Therefore, we suppose that EDPs produced by NE may be involved in NAFLD progression.…”

Section: Increase Of Ne Activity Is Responsible For Elastin Fragmentamentioning

confidence: 84%

“…This widely expressed receptor complex comprises a peripheral EDP-binding subunit, the so-called elastin binding protein (EBP), a protective protein/cathepsin A, and neuraminidase-1 (Neu-1), whose enzymatic activity is required for ERC signaling (7). Elastin knockout mice have been shown to exhibit diabetes (8), suggesting that elastic fiber aging may influence the development of diseases characteristic of the metabolic syndrome. Nevertheless, no study has yet investigated the role of EDPs and their receptors in liver physiology and NASH development.…”

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confidence: 99%

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Production of Elastin-Derived Peptides Contributes to the Development of Nonalcoholic Steatohepatitis

et al. 2018

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Affecting more than 30% of the Western population, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including nonalcoholic steatohepatitis (NASH), cancer, hypertension, and atherosclerosis. Insulin resistance and obesity are described as potential causes of NAFLD. However, we surmised that factors such as extracellular matrix remodeling of large blood vessels, skin, or lungs may also participate in the progression of liver diseases. We studied the effects of elastin-derived peptides (EDPs), biomarkers of aging, on NAFLD progression. We evaluated the consequences of EDP accumulation in mice and of elastin receptor complex (ERC) activation on lipid storage in hepatocytes, inflammation, and fibrosis development. The accumulation of EDPs induces hepatic lipogenesis (i.e., SREBP1c and ACC), inflammation (i.e., Kupffer cells, IL-1β, and TGF-β), and fibrosis (collagen and elastin expression). These effects are induced by inhibition of the LKB1-AMPK pathway by ERC activation. In addition, pharmacological inhibitors of EDPs demonstrate that this EDP-driven lipogenesis and fibrosis relies on engagement of the ERC. Our data reveal a major role of EDPs in the development of NASH, and they provide new clues for understanding the relationship between NAFLD and vascular aging.

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Section: Increase Of Ne Activity Is Responsible For Elastin Fragmentamentioning

confidence: 84%

mentioning

confidence: 99%

Production of Elastin-Derived Peptides Contributes to the Development of Nonalcoholic Steatohepatitis

et al. 2018

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“…In detail, MMP-12 (macrophage elastase) is one of the major MMPs degrading elastin in mice [88]. Under HFD, CD11c adipose macrophages (M2) express immense levels of MMP-12 [68,89]; although the literature supports that elastin downregulation aggravates IR in obese WAT [90,91].…”

Section: Structure Of Extracellular Matrix In the Adipose Tissue Amentioning

confidence: 99%

Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases

Ruiz‐Ojeda

Méndez-Gutiérrez

Aguilera

et al. 2019

IJMS

182

154

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The extracellular matrix (ECM) is a network of different proteins and proteoglycans that controls differentiation, migration, repair, survival, and development, and it seems that its remodeling is required for healthy adipose tissue expansion. Obesity drives an excessive lipid accumulation in adipocytes, which provokes immune cells infiltration, fibrosis (an excess of deposition of ECM components such as collagens, elastin, and fibronectin) and inflammation, considered a consequence of local hypoxia, and ultimately insulin resistance. To understand the mechanism of this process is a challenge to treat the metabolic diseases. This review is focused at identifying the putative role of ECM in adipose tissue, describing its structure and components, its main tissue receptors, and how it is affected in obesity, and subsequently the importance of an appropriate ECM remodeling in adipose tissue expansion to prevent metabolic diseases.

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“…Eln ϩ/Ϫ mice have indications of diastolic dysfunction, which may be linked to compromised arterial Windkessel function and decreased cardiac perfusion during diastole (95). Eln ϩ/Ϫ mice have impaired glucose metabolism (28) and altered susceptibility to atherosclerotic plaque accumulation (108,174). Genetic modifiers of the Eln ϩ/Ϫ cardiovascular phenotype have been identified by outcrossing Eln ϩ/Ϫ mice.…”

Section: Mouse Models Of Genetic Elastinopathiesmentioning

confidence: 99%

Elastin, arterial mechanics, and cardiovascular disease

Cocciolone

Hawes

Staiculescu

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

230

161

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Large, elastic arteries are composed of cells and a specialized extracellular matrix that provides reversible elasticity and strength. Elastin is the matrix protein responsible for this reversible elasticity that reduces the workload on the heart and dampens pulsatile flow in distal arteries. Here, we summarize the elastin protein biochemistry, self-association behavior, cross-linking process, and multistep elastic fiber assembly that provide large arteries with their unique mechanical properties. We present measures of passive arterial mechanics that depend on elastic fiber amounts and integrity such as the Windkessel effect, structural and material stiffness, and energy storage. We discuss supravalvular aortic stenosis and autosomal dominant cutis laxa-1, which are genetic disorders caused by mutations in the elastin gene. We present mouse models of supravalvular aortic stenosis, autosomal dominant cutis laxa-1, and graded elastin amounts that have been invaluable for understanding the role of elastin in arterial mechanics and cardiovascular disease. We summarize acquired diseases associated with elastic fiber defects, including hypertension and arterial stiffness, diabetes, obesity, atherosclerosis, calcification, and aneurysms and dissections. We mention animal models that have helped delineate the role of elastic fiber defects in these acquired diseases. We briefly summarize challenges and recent advances in generating functional elastic fibers in tissue-engineered arteries. We conclude with suggestions for future research and opportunities for therapeutic intervention in genetic and acquired elastinopathies.

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Elastin Insufficiency Predisposes Mice to Impaired Glucose Metabolism

Cited by 8 publications

References 29 publications

Production of Elastin-Derived Peptides Contributes to the Development of Nonalcoholic Steatohepatitis

Production of Elastin-Derived Peptides Contributes to the Development of Nonalcoholic Steatohepatitis

Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases

Elastin, arterial mechanics, and cardiovascular disease

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