Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]

Publication Date:
2018-04-26
Publisher:
American Heart Association (AHA)
Print ISSN:
1079-5642
Electronic ISSN:
1524-4636
Topics:
Medicine
Keywords:
Cell Biology/Structural Biology, Inflammation, Atherosclerosis
Published by:
http://www.americanheart.org/
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autor Samantha E. Adamson, Renata Polanowska-Grabowska, Kathryn Marqueen, Rachael Griffiths, Jerry Angdisen, Sarah R. Breevoort, Ira G. Schulman, Norbert Leitinger
beschreibung Objective—Inflammatory macrophages promote the development of atherosclerosis. We have identified the adaptor protein Dab2 (disabled homolog 2) as a regulator of phenotypic polarization in macrophages. The absence of Dab2 in myeloid cells promotes an inflammatory phenotype, but the impact of myeloid Dab2 deficiency on atherosclerosis has not been shown.Approach and Results—To determine the role of myeloid Dab2 in atherosclerosis, Ldlr−/− mice were reconstituted with either Dab2-positive or Dab2-deficient bone marrow and fed a western diet. Consistent with our previous finding that Dab2 inhibits NFκB (nuclear factor κ-light-chain-enhancer of activated B cells) signaling in macrophages, Ldlr−/− mice reconstituted with Dab2-deficient bone marrow had increased systemic inflammation as evidenced by increased serum IL-6 (interleukin-6) levels and increased inflammatory cytokine expression levels in liver. Serum lipid levels were significantly lower in Ldlr−/− mice reconstituted with Dab2-deficient bone marrow, and further examination of livers from these mice revealed drastically increased inflammatory tissue damage and massive infiltration of immune cells. Surprisingly, the atherosclerotic lesion burden in Ldlr−/− mice reconstituted with Dab2-deficient bone marrow was decreased compared with Ldlr−/− mice reconstituted with wild-type bone marrow. Further analysis of aortic root sections revealed increased macrophage content and evidence of increased apoptosis in lesions from Ldlr−/− mice reconstituted with Dab2-deficient bone marrow but no difference in collagen or α-smooth muscle actin content.Conclusions—Dab2 deficiency in myeloid cells promotes inflammation in livers and atherosclerotic plaques in a mouse model of atherosclerosis. Nevertheless, decreased serum lipids as a result of massive inflammatory liver damage may preclude an appreciable increase in atherosclerotic lesion burden in mice reconstituted with Dab2-deficient bone marrow.
citation_standardnr 6244206
datenlieferant ipn_articles
feed_id 324
feed_publisher American Heart Association (AHA)
feed_publisher_url http://www.americanheart.org/
insertion_date 2018-04-26
journaleissn 1524-4636
journalissn 1079-5642
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Heart Association (AHA)
quelle Arteriosclerosis, Thrombosis, and Vascular Biology
relation http://atvb.ahajournals.org/content/38/5/1020.short?rss=1
schlagwort Cell Biology/Structural Biology, Inflammation, Atherosclerosis
search_space articles
shingle_author_1 Samantha E. Adamson, Renata Polanowska-Grabowska, Kathryn Marqueen, Rachael Griffiths, Jerry Angdisen, Sarah R. Breevoort, Ira G. Schulman, Norbert Leitinger
shingle_author_2 Samantha E. Adamson, Renata Polanowska-Grabowska, Kathryn Marqueen, Rachael Griffiths, Jerry Angdisen, Sarah R. Breevoort, Ira G. Schulman, Norbert Leitinger
shingle_author_3 Samantha E. Adamson, Renata Polanowska-Grabowska, Kathryn Marqueen, Rachael Griffiths, Jerry Angdisen, Sarah R. Breevoort, Ira G. Schulman, Norbert Leitinger
shingle_author_4 Samantha E. Adamson, Renata Polanowska-Grabowska, Kathryn Marqueen, Rachael Griffiths, Jerry Angdisen, Sarah R. Breevoort, Ira G. Schulman, Norbert Leitinger
shingle_catch_all_1 Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]
Cell Biology/Structural Biology, Inflammation, Atherosclerosis
Objective—Inflammatory macrophages promote the development of atherosclerosis. We have identified the adaptor protein Dab2 (disabled homolog 2) as a regulator of phenotypic polarization in macrophages. The absence of Dab2 in myeloid cells promotes an inflammatory phenotype, but the impact of myeloid Dab2 deficiency on atherosclerosis has not been shown.Approach and Results—To determine the role of myeloid Dab2 in atherosclerosis, Ldlr−/− mice were reconstituted with either Dab2-positive or Dab2-deficient bone marrow and fed a western diet. Consistent with our previous finding that Dab2 inhibits NFκB (nuclear factor κ-light-chain-enhancer of activated B cells) signaling in macrophages, Ldlr−/− mice reconstituted with Dab2-deficient bone marrow had increased systemic inflammation as evidenced by increased serum IL-6 (interleukin-6) levels and increased inflammatory cytokine expression levels in liver. Serum lipid levels were significantly lower in Ldlr−/− mice reconstituted with Dab2-deficient bone marrow, and further examination of livers from these mice revealed drastically increased inflammatory tissue damage and massive infiltration of immune cells. Surprisingly, the atherosclerotic lesion burden in Ldlr−/− mice reconstituted with Dab2-deficient bone marrow was decreased compared with Ldlr−/− mice reconstituted with wild-type bone marrow. Further analysis of aortic root sections revealed increased macrophage content and evidence of increased apoptosis in lesions from Ldlr−/− mice reconstituted with Dab2-deficient bone marrow but no difference in collagen or α-smooth muscle actin content.Conclusions—Dab2 deficiency in myeloid cells promotes inflammation in livers and atherosclerotic plaques in a mouse model of atherosclerosis. Nevertheless, decreased serum lipids as a result of massive inflammatory liver damage may preclude an appreciable increase in atherosclerotic lesion burden in mice reconstituted with Dab2-deficient bone marrow.
Samantha E. Adamson, Renata Polanowska-Grabowska, Kathryn Marqueen, Rachael Griffiths, Jerry Angdisen, Sarah R. Breevoort, Ira G. Schulman, Norbert Leitinger
American Heart Association (AHA)
1079-5642
10795642
1524-4636
15244636
shingle_catch_all_2 Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]
Cell Biology/Structural Biology, Inflammation, Atherosclerosis
Objective—Inflammatory macrophages promote the development of atherosclerosis. We have identified the adaptor protein Dab2 (disabled homolog 2) as a regulator of phenotypic polarization in macrophages. The absence of Dab2 in myeloid cells promotes an inflammatory phenotype, but the impact of myeloid Dab2 deficiency on atherosclerosis has not been shown.Approach and Results—To determine the role of myeloid Dab2 in atherosclerosis, Ldlr−/− mice were reconstituted with either Dab2-positive or Dab2-deficient bone marrow and fed a western diet. Consistent with our previous finding that Dab2 inhibits NFκB (nuclear factor κ-light-chain-enhancer of activated B cells) signaling in macrophages, Ldlr−/− mice reconstituted with Dab2-deficient bone marrow had increased systemic inflammation as evidenced by increased serum IL-6 (interleukin-6) levels and increased inflammatory cytokine expression levels in liver. Serum lipid levels were significantly lower in Ldlr−/− mice reconstituted with Dab2-deficient bone marrow, and further examination of livers from these mice revealed drastically increased inflammatory tissue damage and massive infiltration of immune cells. Surprisingly, the atherosclerotic lesion burden in Ldlr−/− mice reconstituted with Dab2-deficient bone marrow was decreased compared with Ldlr−/− mice reconstituted with wild-type bone marrow. Further analysis of aortic root sections revealed increased macrophage content and evidence of increased apoptosis in lesions from Ldlr−/− mice reconstituted with Dab2-deficient bone marrow but no difference in collagen or α-smooth muscle actin content.Conclusions—Dab2 deficiency in myeloid cells promotes inflammation in livers and atherosclerotic plaques in a mouse model of atherosclerosis. Nevertheless, decreased serum lipids as a result of massive inflammatory liver damage may preclude an appreciable increase in atherosclerotic lesion burden in mice reconstituted with Dab2-deficient bone marrow.
Samantha E. Adamson, Renata Polanowska-Grabowska, Kathryn Marqueen, Rachael Griffiths, Jerry Angdisen, Sarah R. Breevoort, Ira G. Schulman, Norbert Leitinger
American Heart Association (AHA)
1079-5642
10795642
1524-4636
15244636
shingle_catch_all_3 Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]
Cell Biology/Structural Biology, Inflammation, Atherosclerosis
Objective—Inflammatory macrophages promote the development of atherosclerosis. We have identified the adaptor protein Dab2 (disabled homolog 2) as a regulator of phenotypic polarization in macrophages. The absence of Dab2 in myeloid cells promotes an inflammatory phenotype, but the impact of myeloid Dab2 deficiency on atherosclerosis has not been shown.Approach and Results—To determine the role of myeloid Dab2 in atherosclerosis, Ldlr−/− mice were reconstituted with either Dab2-positive or Dab2-deficient bone marrow and fed a western diet. Consistent with our previous finding that Dab2 inhibits NFκB (nuclear factor κ-light-chain-enhancer of activated B cells) signaling in macrophages, Ldlr−/− mice reconstituted with Dab2-deficient bone marrow had increased systemic inflammation as evidenced by increased serum IL-6 (interleukin-6) levels and increased inflammatory cytokine expression levels in liver. Serum lipid levels were significantly lower in Ldlr−/− mice reconstituted with Dab2-deficient bone marrow, and further examination of livers from these mice revealed drastically increased inflammatory tissue damage and massive infiltration of immune cells. Surprisingly, the atherosclerotic lesion burden in Ldlr−/− mice reconstituted with Dab2-deficient bone marrow was decreased compared with Ldlr−/− mice reconstituted with wild-type bone marrow. Further analysis of aortic root sections revealed increased macrophage content and evidence of increased apoptosis in lesions from Ldlr−/− mice reconstituted with Dab2-deficient bone marrow but no difference in collagen or α-smooth muscle actin content.Conclusions—Dab2 deficiency in myeloid cells promotes inflammation in livers and atherosclerotic plaques in a mouse model of atherosclerosis. Nevertheless, decreased serum lipids as a result of massive inflammatory liver damage may preclude an appreciable increase in atherosclerotic lesion burden in mice reconstituted with Dab2-deficient bone marrow.
Samantha E. Adamson, Renata Polanowska-Grabowska, Kathryn Marqueen, Rachael Griffiths, Jerry Angdisen, Sarah R. Breevoort, Ira G. Schulman, Norbert Leitinger
American Heart Association (AHA)
1079-5642
10795642
1524-4636
15244636
shingle_catch_all_4 Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]
Cell Biology/Structural Biology, Inflammation, Atherosclerosis
Objective—Inflammatory macrophages promote the development of atherosclerosis. We have identified the adaptor protein Dab2 (disabled homolog 2) as a regulator of phenotypic polarization in macrophages. The absence of Dab2 in myeloid cells promotes an inflammatory phenotype, but the impact of myeloid Dab2 deficiency on atherosclerosis has not been shown.Approach and Results—To determine the role of myeloid Dab2 in atherosclerosis, Ldlr−/− mice were reconstituted with either Dab2-positive or Dab2-deficient bone marrow and fed a western diet. Consistent with our previous finding that Dab2 inhibits NFκB (nuclear factor κ-light-chain-enhancer of activated B cells) signaling in macrophages, Ldlr−/− mice reconstituted with Dab2-deficient bone marrow had increased systemic inflammation as evidenced by increased serum IL-6 (interleukin-6) levels and increased inflammatory cytokine expression levels in liver. Serum lipid levels were significantly lower in Ldlr−/− mice reconstituted with Dab2-deficient bone marrow, and further examination of livers from these mice revealed drastically increased inflammatory tissue damage and massive infiltration of immune cells. Surprisingly, the atherosclerotic lesion burden in Ldlr−/− mice reconstituted with Dab2-deficient bone marrow was decreased compared with Ldlr−/− mice reconstituted with wild-type bone marrow. Further analysis of aortic root sections revealed increased macrophage content and evidence of increased apoptosis in lesions from Ldlr−/− mice reconstituted with Dab2-deficient bone marrow but no difference in collagen or α-smooth muscle actin content.Conclusions—Dab2 deficiency in myeloid cells promotes inflammation in livers and atherosclerotic plaques in a mouse model of atherosclerosis. Nevertheless, decreased serum lipids as a result of massive inflammatory liver damage may preclude an appreciable increase in atherosclerotic lesion burden in mice reconstituted with Dab2-deficient bone marrow.
Samantha E. Adamson, Renata Polanowska-Grabowska, Kathryn Marqueen, Rachael Griffiths, Jerry Angdisen, Sarah R. Breevoort, Ira G. Schulman, Norbert Leitinger
American Heart Association (AHA)
1079-5642
10795642
1524-4636
15244636
shingle_title_1 Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]
shingle_title_2 Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]
shingle_title_3 Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]
shingle_title_4 Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]
timestamp 2025-06-30T23:34:33.463Z
titel Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]
titel_suche Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief ReportHighlights [Basic Sciences]
topic WW-YZ
uid ipn_articles_6244206