Journal Article

DZNE-2020-05025

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Ursodeoxycholic acid impairs atherogenesis and promotes plaque regression by cholesterol crystal dissolution in mice.

Bode, N. ; Grebe, A. ; Kerksiek, A. ; Lütjohann, D. ; Werner, N. ; Nickenig, G. ; Latz, E.DZNE* ; Zimmer, S. (Corresponding author)

2016
Academic Press Orlando, Fla.

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Please use a persistent id in citations: doi:10.1016/j.bbrc.2016.07.047

Abstract: Atherosclerosis is a chronic inflammatory disease driven primarily by a continuous retention of cholesterol within the subendothelial space where it precipitates to form cholesterol crystals (CC). These CC trigger a complex inflammatory response through activation of the NLRP3 inflammasome and promote lesion development. Here we examined whether increasing cholesterol solubility with ursodeoxycholic acid (UDCA) affects vascular CC formation and ultimately atherosclerotic lesion development. UDCA mediated intracellular CC dissolution in macrophages and reduced IL-1β production. In ApoE(-/-) mice, UDCA treatment not only impaired atherosclerotic plaque development but also mediated regression of established vascular lesions. Importantly, mice treated with UDCA had decreased CC-depositions in atherosclerotic plaques compared to controls. Together, our data demonstrate that UDCA impaired CC and NLRP3 dependent inflammation by increasing cholesterol solubility and diminished atherosclerosis in mice.

Keyword(s): Animals (MeSH) ; Atherosclerosis: drug therapy (MeSH) ; Atherosclerosis: metabolism (MeSH) ; Atherosclerosis: pathology (MeSH) ; Cholagogues and Choleretics: administration & dosage (MeSH) ; Cholesterol: chemistry (MeSH) ; Cholesterol: metabolism (MeSH) ; Crystallization (MeSH) ; Dose-Response Relationship, Drug (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; NLR Family, Pyrin Domain-Containing 3 Protein: metabolism (MeSH) ; Plaque, Atherosclerotic: drug therapy (MeSH) ; Plaque, Atherosclerotic: metabolism (MeSH) ; Plaque, Atherosclerotic: pathology (MeSH) ; Treatment Outcome (MeSH) ; Ursodeoxycholic Acid: administration & dosage (MeSH) ; Ursodeoxycholic Acid: chemistry (MeSH) ; Cholagogues and Choleretics ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nlrp3 protein, mouse ; Ursodeoxycholic Acid ; Cholesterol

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Contributing Institute(s):

1. Innate Immunity in Neurodegeneration (AG Latz)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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