Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice

Donners, Marjo M. P. C.; Bai, Lili; Lutgens, Suzanne P. M.; Wijnands, Erwin; Johnson, Jason L.; Schurgers, Leon J.; Liu, Cong-Lin; Daemen, Mat J.A.P.; Cleutjens, Kitty B.J.M.; Shi, Guo‐Ping; Biessen, Erik A. L.; Heeneman, Sylvia

doi:10.1371/journal.pone.0162595

Cited by 9 publications

(9 citation statements)

References 29 publications

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“…It aims at minimizing potential complications which may ultimately lead to patient mortality. For instance, it aims to avoid hypovolemia, electrolyte imbalance, renal insufficiency and sepsis [24].…”

Section: Resultsmentioning

confidence: 99%

“…When cutaneous areas are nondetached, the must be kept dry and not manipulated. However, detached cutaneous areas should be covered with Vaseline gauze until reepithelization has occurred [24].…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, there was delayed wound healing in mice with a fibroblastspecific deletion of integrin B1, which binds extracellular matrix proteins, in mice that lack superoxide dismutase, an important ant oxidative enzyme, or IL-6 in mice that lack Toll-like Receptor 3, and have a defective recruitment of neutrophils and macrophages [23]. When mice lack matrix metalloproteinases, which degrade extracellular matrix proteins, or when mice are deficient in Natural Killer (NK) or T Cells, there is accelerated wound healing [24].…”

Section: Insights From Animals On the Immune System And Wound Healingmentioning

confidence: 99%

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Wound Care in Immunobullous Disease

Nadelmann¹,

Czernik²

2018

Autoimmune Bullous Diseases

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The chapter introduces the steps to achieving proper wound care in immunobullous disease. It describes the clinical characteristics and nature of "wounds" formed in pemphigus versus pemphigoid diseases. Namely, pemphigus diseases typically result in acantholysis in the epidermis and the formation of flaccid blisters. In contrast, bullous pemphigoid presents with basal keratinocyte hemidesmosomes in the dermoepidermal junction, which results in a split at the dermoepidermal junction and clinically forms tense blisters. Therefore, there is a separate protocol for treating the wounds in each of these diseases, which must take additional patient specific factors into consideration.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Insights From Animals On the Immune System And Wound Healingmentioning

confidence: 99%

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Wound Care in Immunobullous Disease

Nadelmann¹,

Czernik²

2018

Autoimmune Bullous Diseases

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“…The results of a recent study using a murine vein graft model suggested that CatS also contributes to vascular SMC proliferation and macrophage migration through degradation of elastic lamina to facilitate vein graft neointimal hyperplasia 59 ) . The role of cathepsins in neointima formation is further supported by the direct evidence that genetic deletions of CatS 60 , 61) ) and CatK 62 ) reduced neointimal lesion formation in response to injury, indicating a novel therapeutic strategy for the treatment of endovascular therapy-related restenosis by regulating CatS or CatK activity. Moreover, it has also been demonstrated that CatS and CatK degrade fibronectin, collagen type I, and laminin, and that the ability of SMCs transmigration through a basement membrane matrix gel can be inhibited by a selective Cat inhibitor 17 , 22 , 63 – 65 ) .…”

Section: Cathepsins In Restenosismentioning

confidence: 89%

Cysteine Protease Cathepsins in Atherosclerotic Cardiovascular Diseases

Dai

et al. 2018

J Atheroscler Thromb

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Atherosclerotic cardiovascular disease (ASCVD) is an inflammatory disease characterized by extensive arterial wall matrix protein degradation. Cysteine protease cathepsins play a pivotal role in extracellular matrix (ECM) remodeling and have been implicated in the development and progression of atherosclerosis-based cardiovascular diseases. An imbalance in expression between cathepsins (such as cathepsins S, K, L, C) and their inhibitor cystatin C may favor proteolysis of ECM in the pathogenesis of cardiovascular disease such as atherosclerosis, aneurysm formation, restenosis, and neovascularization. New insights into cathepsin functions have been made possible by the generation of knock-out mice and by the application of specific inhibitors. Inflammatory cytokines regulate the expression and activities of cathepsins in cultured vascular cells and macrophages. In addition, evaluations of the possibility of cathepsins as a diagnostic tool revealed that the circulating levels of cathepsin S, K, and L, and their endogenous inhibitor cystatin C could be promising biomarkers in the diagnosis of coronary artery disease, aneurysm, adiposity, peripheral arterial disease, and coronary artery calcification. In this review, we summarize the available information regarding the mechanistic contributions of cathepsins to ASCVD.

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“…All stainings were performed on adjacent plaque sections for vascular endothelial marker CD31 (Dako), macrophage marker CD68 (Dako), T-cell marker CD3 (Dako) and MGC marker (cathepsin K 41 ). MGCs were defined as cathepsin-K positive cells having 2 or more round nuclei.…”

Section: Methodsmentioning

confidence: 99%

Low human and murine Mcl-1 expression leads to a pro-apoptotic plaque phenotype enriched in giant-cells

Fontaine

Westra

Bot

et al. 2019

Sci Rep

Self Cite

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The anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) plays an important role in survival and differentiation of leukocytes, more specifically of neutrophils. Here, we investigated the impact of myeloid Mcl-1 deletion in atherosclerosis. Western type diet fed LDL receptor-deficient mice were transplanted with either wild-type (WT) or LysMCre Mcl-1fl/fl (Mcl-1−/−) bone marrow. Mcl-1 myeloid deletion resulted in enhanced apoptosis and lipid accumulation in atherosclerotic plaques. In vitro, Mcl-1 deficient macrophages also showed increased lipid accumulation, resulting in increased sensitivity to lipid-induced cell death. However, plaque size, necrotic core and macrophage content were similar in Mcl-1−/− compared to WT mice, most likely due to decreased circulating and plaque-residing neutrophils. Interestingly, Mcl-1−/− peritoneal foam cells formed up to 45% more multinucleated giant cells (MGCs) in vitro compared to WT, which concurred with an increased MGC presence in atherosclerotic lesions of Mcl-1−/− mice. Moreover, analysis of human unstable atherosclerotic lesions also revealed a significant inverse correlation between MGC lesion content and Mcl-1 gene expression, coinciding with the mouse data. Taken together, these findings suggest that myeloid Mcl-1 deletion leads to a more apoptotic, lipid and MGC-enriched phenotype. These potentially pro-atherogenic effects are however counteracted by neutropenia in circulation and plaque.

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Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice

Cited by 9 publications

References 29 publications

Wound Care in Immunobullous Disease

Wound Care in Immunobullous Disease

Cysteine Protease Cathepsins in Atherosclerotic Cardiovascular Diseases

Low human and murine Mcl-1 expression leads to a pro-apoptotic plaque phenotype enriched in giant-cells

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