Bone marrow‐specific caspase‐1/11 deficiency inhibits atherosclerosis development in Ldlr−/− mice

Hendrikx, Tim; Jeurissen, Mike L. J.; Gorp, Patrick J. van; Gijbels, Marion J.J.; Walenbergh, Sofie M. A.; Houben, Tom; Gorp, Rick van; Pöttgens, Chantal; Stienstra, Rinke; Netea, Mihai G.; Hofker, Marten H.; Donners, Marjo M. P. C.; Shiri-Sverdlov, Ronit

doi:10.1111/febs.13279

Cited by 62 publications

(44 citation statements)

References 37 publications

(55 reference statements)

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“…Bone marrow-derived macrophages (BMDMs) were isolated as described previously26. Cells were grown in 12-well plates (Greiner Bio-One) on coverslips (Ø 20 mm; Thermo Scientific).…”

Section: Methodsmentioning

confidence: 99%

Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

Walenbergh

Houben

Rensen

et al. 2016

Sci Rep

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Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver. Yet, the link between plasma CatD to adult NASH was not examined. In the current manuscript, we investigated whether plasma CatD in adults correlates with NASH development and regression. Biopsies were histologically evaluated for inflammation and NAFLD in three complementary cohorts of adults (total n = 248). CatD and alanine aminotransferase (ALT) were measured in plasma. Opposite to our previous observations with childhood NASH, we observed increased levels of plasma CatD in patients with NASH compared to adults without hepatic inflammation. Furthermore, after surgical intervention, we found a reduction of plasma CatD compared to baseline. Our observations highlight a distinct pathophysiology between NASH in children and adults. The observation that plasma CatD correlated with NASH development and regression is promising for NASH diagnosis.

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“…Bone marrow-derived macrophages (BMDMs) were isolated as described previously26. Cells were grown in 12-well plates (Greiner Bio-One) on coverslips (Ø 20 mm; Thermo Scientific).…”

Section: Methodsmentioning

confidence: 99%

Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

Walenbergh

Houben

Rensen

et al. 2016

Sci Rep

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“…In particular, NLR pyrin domain containing 3 (NLRP3), a member of the NLR family, recognizes various DAMPs to form an NLRP3 inflammasome molecular complex in the cytosol and leads to inflammatory responses. Indeed, recent studies demonstrated that NLRP3 inflammasome-driven inflammatory responses contributed to the progression of atherosclerosis 10–13) . This study highlighted the present state of knowledge on the role of NLRP3 inflammasomes in the pathogenesis of atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Role of NLRP3 Inflammasomes in Atherosclerosis

Karasawa

Takahashi

2017

J Atheroscler Thromb

228

155

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Inflammation with macrophage infiltration is a key feature of atherosclerosis. Although the mechanisms had been unclear, emerging evidence unveiled that NLRP3 inflammasomes, which regulate caspase-1 activation and subsequent processing of pro-IL-1β, trigger vascular wall inflammatory responses and lead to progression of atherosclerosis. NLRP3 inflammasomes are activated by various danger signals, such as cholesterol crystals, calcium phosphate crystals, and oxidized low-density lipoprotein in macrophages, to initiate inflammatory responses in the atherosclerotic lesion. Recent studies have further clarified the regulatory mechanisms and the potential therapeutic agents that target NLRP3 inflammasomes. In this study, we reviewed the present state of knowledge on the role of NLRP3 inflammasomes in the pathogenesis of atherosclerosis and discussed the therapeutic approaches that target NLRP3 inflammasomes.

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“…Reducing the lipid core within the plaque improves plaque stability [72]. Also, specifically silencing mouse bone marrow caspase-1/11 gene can significantly reduce the necrotic lipid core of plaque and enhance plaque stability [81]. Studies have found that MCC950, an NLRP3 inflammation inhibitor, can significantly improve the stability of mouse platelets because it inhibits the inflammatory response of macrophages [82].…”

Section: Nlrp3 Inflammasome Andmentioning

confidence: 99%

NLRP3 Inflammasome: A Potential Alternative Therapy Target for Atherosclerosis

Yang

Yin

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Atherosclerosis (AS) is a complex and chronic inflammatory disease that occurs in multiple systems of the human body. It is an important pathological basis for a variety of diseases and a serious threat to human health. So far, many theories have been formed to explain the pathogenesis of atherosclerosis, among which “inflammation theory” has gradually become a research focus. This theory presents that inflammatory response runs through the whole progress of AS, inflammatory cells play as the main executors of AS, and inflammatory mediators are the key molecules of AS. In the inflammatory process of atherosclerosis, the role of NLRP3 in the atherosclerosis has gradually got the attention of researchers. NLRP3 is a kind of signal-transductional pattern recognition receptors (PRRs). After recognizing and binding to the damage factors, NLRP3 inflammasome will be assembled to activate IL-1β and caspase-1 pathways, resulting in promoting the inflammation process of AS, reducing the stability of the plaques, and finally increasing the incidence of adverse cardiovascular events. Taken above, the article will review the potential benefits of drugs targeting the NLRP3 inflammasome in the therapy of AS.

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Bone marrow‐specific caspase‐1/11 deficiency inhibits atherosclerosis development in Ldlr^−/− mice

Cited by 62 publications

References 37 publications

Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

Role of NLRP3 Inflammasomes in Atherosclerosis

NLRP3 Inflammasome: A Potential Alternative Therapy Target for Atherosclerosis

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