Deficiency of Nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 reduces atherosclerosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-06-25

AUTHORS

Ann-Kathrin Vlacil, Jutta Schuett, Volker Ruppert, Muhidien Soufi, Raghav Oberoi, Kinan Shahin, Christian Wächter, Thomas Tschernig, Yu Lei, Fan Liu, Uwe J. F. Tietge, Bernhard Schieffer, Harald Schuett, Karsten Grote

ABSTRACT

Atherosclerosis is crucially fueled by inflammatory pathways including pattern recognition receptor (PRR)-related signaling of the innate immune system. Currently, the impact of the cytoplasmic PRRs nucleotide-binding oligomerization domain-containing protein (NOD) 1 and 2 is incompletely characterized. We, therefore, generated Nod1/Nod2 double knockout mice on a low-density lipoprotein receptor (Ldlr)-deficient background (= Ldlr−/−Nod1/2−/−) which were subsequently analyzed regarding experimental atherosclerosis, lipid metabolism, insulin resistance and gut microbiota composition. Compared to Ldlr−/− mice, Ldlr−/−Nod1/2−/− mice showed reduced plasma lipids and increased hepatic expression of the scavenger receptor LDL receptor-related protein 1 after feeding a high-fat diet for 12 weeks. Furthermore, intestinal cholesterol and its bacterial degradation product coprostanol were elevated in Ldlr−/−Nod1/2−/− mice, correlating with the increased abundance of Eubacterium coprostanoligenes as assessed by 3rd generation sequencing of the gut microbiota. Atherosclerotic plaques of Ldlr−/−Nod1/2−/− mice exhibited less lipid deposition and macrophage accumulation. Moreover, macrophages from Ldlr−/−Nod1/2−/− mice showed higher expression of the cholesterol efflux transporters Abca1 and Abcg1 and accordingly reduced foam cell formation. Deficiency of Nod1 and Nod2 led to reduced plaque lipid deposition and inflammatory cell infiltration in atherosclerotic plaques. This might be explained by diminished plasma lipid levels and foam cell formation due to altered expression of key regulators of the hepatic cholesterol pathway as well as differential intestinal cholesterol metabolism and microbiota composition. More... »

PAGES

47

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00395-020-0806-2

DOI

http://dx.doi.org/10.1007/s00395-020-0806-2

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32588196


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20 schema:description Atherosclerosis is crucially fueled by inflammatory pathways including pattern recognition receptor (PRR)-related signaling of the innate immune system. Currently, the impact of the cytoplasmic PRRs nucleotide-binding oligomerization domain-containing protein (NOD) 1 and 2 is incompletely characterized. We, therefore, generated Nod1/Nod2 double knockout mice on a low-density lipoprotein receptor (Ldlr)-deficient background (= Ldlr−/−Nod1/2−/−) which were subsequently analyzed regarding experimental atherosclerosis, lipid metabolism, insulin resistance and gut microbiota composition. Compared to Ldlr−/− mice, Ldlr−/−Nod1/2−/− mice showed reduced plasma lipids and increased hepatic expression of the scavenger receptor LDL receptor-related protein 1 after feeding a high-fat diet for 12 weeks. Furthermore, intestinal cholesterol and its bacterial degradation product coprostanol were elevated in Ldlr−/−Nod1/2−/− mice, correlating with the increased abundance of Eubacterium coprostanoligenes as assessed by 3rd generation sequencing of the gut microbiota. Atherosclerotic plaques of Ldlr−/−Nod1/2−/− mice exhibited less lipid deposition and macrophage accumulation. Moreover, macrophages from Ldlr−/−Nod1/2−/− mice showed higher expression of the cholesterol efflux transporters Abca1 and Abcg1 and accordingly reduced foam cell formation. Deficiency of Nod1 and Nod2 led to reduced plaque lipid deposition and inflammatory cell infiltration in atherosclerotic plaques. This might be explained by diminished plasma lipid levels and foam cell formation due to altered expression of key regulators of the hepatic cholesterol pathway as well as differential intestinal cholesterol metabolism and microbiota composition.
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26 schema:keywords ABCA1
27 ABCG1
28 Eubacterium coprostanoligenes
29 LDL receptor-related protein 1
30 NOD1
31 NOD2
32 PRRS
33 abundance
34 accumulation
35 altered expression
36 atherosclerosis
37 atherosclerotic plaques
38 background
39 cell formation
40 cell infiltration
41 cholesterol
42 cholesterol efflux transporters ABCA1
43 cholesterol metabolism
44 cholesterol pathway
45 composition
46 coprostanol
47 deficiency
48 deficient background
49 deposition
50 diet
51 domain-containing protein 1
52 double knockout mice
53 experimental atherosclerosis
54 expression
55 foam cell formation
56 formation
57 generation sequencing
58 gut microbiota
59 gut microbiota composition
60 hepatic expression
61 high expression
62 high-fat diet
63 immune system
64 impact
65 infiltration
66 inflammatory cell infiltration
67 inflammatory pathways
68 innate immune system
69 insulin resistance
70 intestinal cholesterol
71 intestinal cholesterol metabolism
72 key regulator
73 knockout mice
74 less lipid deposition
75 levels
76 lipid deposition
77 lipid levels
78 lipid metabolism
79 lipids
80 lipoprotein receptor
81 low-density lipoprotein receptor
82 macrophage accumulation
83 macrophages
84 metabolism
85 mice
86 microbiota
87 microbiota composition
88 nucleotides
89 oligomerization domain-containing protein 1
90 pathway
91 pattern recognition receptors
92 plaques
93 plasma lipid levels
94 plasma lipids
95 protein 1
96 receptors
97 recognition receptors
98 regulator
99 resistance
100 sequencing
101 signaling
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103 weeks
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