Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice
Lipopolysaccharide (LPS), which is released from gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in v...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2007-11, Vol.116 (19), p.2173-2181 |
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| creator | WESTERTERP, Marit BERBEE, Jimmy F. P PIRES, Nuno M. M VAN MIERLO, Geertje J. D KLEEMANN, Robert ROMIJN, Johannes A HAVEKES, Louis M RENSEN, Patrick C. N |
| description | Lipopolysaccharide (LPS), which is released from gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated the effect of endogenous apoCI expression on LPS-induced atherosclerosis in mice.
Twelve-week-old apoe-/- apoc1-/- and apoe-/- apoc1+/+ mice received weekly intraperitoneal injections of LPS (50 microg) or vehicle for a period of 10 weeks, and atherosclerosis development was assessed in the aortic root. LPS administration did not affect atherosclerotic lesion area in apoe-/- apoc1-/- mice but increased it in apoe-/- apoc1+/+ mice. In fact, apoCI expression increased the LPS-induced atherosclerotic lesion area by 60% (P |
| doi_str_mv | 10.1161/circulationaha.107.693382 |
| format | Article |
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Twelve-week-old apoe-/- apoc1-/- and apoe-/- apoc1+/+ mice received weekly intraperitoneal injections of LPS (50 microg) or vehicle for a period of 10 weeks, and atherosclerosis development was assessed in the aortic root. LPS administration did not affect atherosclerotic lesion area in apoe-/- apoc1-/- mice but increased it in apoe-/- apoc1+/+ mice. In fact, apoCI expression increased the LPS-induced atherosclerotic lesion area by 60% (P<0.05), concomitant with an increase in LPS-induced plasma levels of fibrinogen and E-selectin. This indicated that apoCI increased the LPS-induced inflammatory state, both systemically (ie, fibrinogen) and at the level of the vessel wall (ie, E-selectin). In addition, both macrophage-derived apoCI and HDL-associated apoCI increased the LPS-induced tumor necrosis factor-alpha response by macrophages in vitro.
We conclude that apoCI is crucially involved in LPS-induced atherosclerosis in apoe-/- mice, which mainly relates to an increased inflammatory response toward LPS. We anticipate that apoCI plasma levels contribute to accelerated atherosclerosis development in individuals who have chronic infection.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/circulationaha.107.693382</identifier><identifier>PMID: 17967778</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Apolipoproteins C - genetics ; Apolipoproteins C - metabolism ; Atherosclerosis (general aspects, experimental research) ; Atherosclerosis - genetics ; Atherosclerosis - immunology ; Atherosclerosis - pathology ; Biological and medical sciences ; Biomarkers - blood ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cells, Cultured ; Cholesterol, HDL - blood ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Drug toxicity and drugs side effects treatment ; E-Selectin - blood ; Female ; Fibrinogen - metabolism ; Hypercholesterolemia - genetics ; Hypercholesterolemia - immunology ; Hypercholesterolemia - pathology ; Lipopolysaccharides - pharmacology ; Macrophages, Peritoneal - metabolism ; Macrophages, Peritoneal - pathology ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Monocytes - pathology ; Pharmacology. Drug treatments ; T-Lymphocytes - pathology ; Toxicity: blood ; Tumor Necrosis Factor-alpha - metabolism ; Vasculitis - genetics ; Vasculitis - immunology ; Vasculitis - pathology</subject><ispartof>Circulation (New York, N.Y.), 2007-11, Vol.116 (19), p.2173-2181</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-93307d489b8a666faf762acd8e0e9ef1b6da59ded1e7b87b823308a74e3169793</citedby><cites>FETCH-LOGICAL-c536t-93307d489b8a666faf762acd8e0e9ef1b6da59ded1e7b87b823308a74e3169793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19281822$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17967778$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WESTERTERP, Marit</creatorcontrib><creatorcontrib>BERBEE, Jimmy F. P</creatorcontrib><creatorcontrib>PIRES, Nuno M. M</creatorcontrib><creatorcontrib>VAN MIERLO, Geertje J. D</creatorcontrib><creatorcontrib>KLEEMANN, Robert</creatorcontrib><creatorcontrib>ROMIJN, Johannes A</creatorcontrib><creatorcontrib>HAVEKES, Louis M</creatorcontrib><creatorcontrib>RENSEN, Patrick C. N</creatorcontrib><title>Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Lipopolysaccharide (LPS), which is released from gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated the effect of endogenous apoCI expression on LPS-induced atherosclerosis in mice.
Twelve-week-old apoe-/- apoc1-/- and apoe-/- apoc1+/+ mice received weekly intraperitoneal injections of LPS (50 microg) or vehicle for a period of 10 weeks, and atherosclerosis development was assessed in the aortic root. LPS administration did not affect atherosclerotic lesion area in apoe-/- apoc1-/- mice but increased it in apoe-/- apoc1+/+ mice. In fact, apoCI expression increased the LPS-induced atherosclerotic lesion area by 60% (P<0.05), concomitant with an increase in LPS-induced plasma levels of fibrinogen and E-selectin. This indicated that apoCI increased the LPS-induced inflammatory state, both systemically (ie, fibrinogen) and at the level of the vessel wall (ie, E-selectin). In addition, both macrophage-derived apoCI and HDL-associated apoCI increased the LPS-induced tumor necrosis factor-alpha response by macrophages in vitro.
We conclude that apoCI is crucially involved in LPS-induced atherosclerosis in apoe-/- mice, which mainly relates to an increased inflammatory response toward LPS. We anticipate that apoCI plasma levels contribute to accelerated atherosclerosis development in individuals who have chronic infection.</description><subject>Animals</subject><subject>Apolipoproteins C - genetics</subject><subject>Apolipoproteins C - metabolism</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Atherosclerosis - genetics</subject><subject>Atherosclerosis - immunology</subject><subject>Atherosclerosis - pathology</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cells, Cultured</subject><subject>Cholesterol, HDL - blood</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>E-Selectin - blood</subject><subject>Female</subject><subject>Fibrinogen - metabolism</subject><subject>Hypercholesterolemia - genetics</subject><subject>Hypercholesterolemia - immunology</subject><subject>Hypercholesterolemia - pathology</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Macrophages, Peritoneal - metabolism</subject><subject>Macrophages, Peritoneal - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Mutant Strains</subject><subject>Monocytes - pathology</subject><subject>Pharmacology. Drug treatments</subject><subject>T-Lymphocytes - pathology</subject><subject>Toxicity: blood</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Vasculitis - genetics</subject><subject>Vasculitis - immunology</subject><subject>Vasculitis - pathology</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtr3DAUhUVpaaZp_0JxF-3OU0uy9VgakzYDQwMlWZs70jWjRrZcyx6YfX54NZ2BkFVA6Pmdc3U5hHyhxZpSQb8bN5nFw-zCAHtY00KuheZcsTdkRStW5mXF9VuyKopC55IzdkU-xPgnHQWX1XtyRaUWUkq1Ik_1GLwbwziFGd2QNfkmczEz02IceH_M3HAI_oA2bbL_YPDHCMbsYXIWczfYxaRXmPc4hWj8aU4GFg_ow9jjMJ-U8LLKTf44BPMYljnrncGP5F0HPuKny3pNHn7c3De3-fbu56apt7mpuJjz1GIhban0ToEQooNOCgbGKixQY0d3wkKlLVqKcqfSYEmgQJbIqdBS82vy7eyb_vF3wTi3vYsGvYcBwxJboUopCy5fBWlyq5goE6jPoEltxwm7dpxcD9OxpUV7yqptNr-bh219v7n7Vd_W6Vq256yS9vOlyLLr0T4rL-Ek4OsFgGjAdxMMxsVnTjNFFWP8H9nfpAg</recordid><startdate>20071106</startdate><enddate>20071106</enddate><creator>WESTERTERP, Marit</creator><creator>BERBEE, Jimmy F. 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Miscellaneous</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>E-Selectin - blood</topic><topic>Female</topic><topic>Fibrinogen - metabolism</topic><topic>Hypercholesterolemia - genetics</topic><topic>Hypercholesterolemia - immunology</topic><topic>Hypercholesterolemia - pathology</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Macrophages, Peritoneal - metabolism</topic><topic>Macrophages, Peritoneal - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Mutant Strains</topic><topic>Monocytes - pathology</topic><topic>Pharmacology. Drug treatments</topic><topic>T-Lymphocytes - pathology</topic><topic>Toxicity: blood</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Vasculitis - genetics</topic><topic>Vasculitis - immunology</topic><topic>Vasculitis - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WESTERTERP, Marit</creatorcontrib><creatorcontrib>BERBEE, Jimmy F. P</creatorcontrib><creatorcontrib>PIRES, Nuno M. M</creatorcontrib><creatorcontrib>VAN MIERLO, Geertje J. D</creatorcontrib><creatorcontrib>KLEEMANN, Robert</creatorcontrib><creatorcontrib>ROMIJN, Johannes A</creatorcontrib><creatorcontrib>HAVEKES, Louis M</creatorcontrib><creatorcontrib>RENSEN, Patrick C. 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N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2007-11-06</date><risdate>2007</risdate><volume>116</volume><issue>19</issue><spage>2173</spage><epage>2181</epage><pages>2173-2181</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Lipopolysaccharide (LPS), which is released from gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated the effect of endogenous apoCI expression on LPS-induced atherosclerosis in mice.
Twelve-week-old apoe-/- apoc1-/- and apoe-/- apoc1+/+ mice received weekly intraperitoneal injections of LPS (50 microg) or vehicle for a period of 10 weeks, and atherosclerosis development was assessed in the aortic root. LPS administration did not affect atherosclerotic lesion area in apoe-/- apoc1-/- mice but increased it in apoe-/- apoc1+/+ mice. In fact, apoCI expression increased the LPS-induced atherosclerotic lesion area by 60% (P<0.05), concomitant with an increase in LPS-induced plasma levels of fibrinogen and E-selectin. This indicated that apoCI increased the LPS-induced inflammatory state, both systemically (ie, fibrinogen) and at the level of the vessel wall (ie, E-selectin). In addition, both macrophage-derived apoCI and HDL-associated apoCI increased the LPS-induced tumor necrosis factor-alpha response by macrophages in vitro.
We conclude that apoCI is crucially involved in LPS-induced atherosclerosis in apoe-/- mice, which mainly relates to an increased inflammatory response toward LPS. We anticipate that apoCI plasma levels contribute to accelerated atherosclerosis development in individuals who have chronic infection.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>17967778</pmid><doi>10.1161/circulationaha.107.693382</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2007-11, Vol.116 (19), p.2173-2181 |
| issn | 0009-7322 1524-4539 |
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| source | MEDLINE; American Heart Association Journals; EZB Electronic Journals Library; Journals@Ovid Complete |
| subjects | Animals Apolipoproteins C - genetics Apolipoproteins C - metabolism Atherosclerosis (general aspects, experimental research) Atherosclerosis - genetics Atherosclerosis - immunology Atherosclerosis - pathology Biological and medical sciences Biomarkers - blood Blood and lymphatic vessels Cardiology. Vascular system Cells, Cultured Cholesterol, HDL - blood Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Drug toxicity and drugs side effects treatment E-Selectin - blood Female Fibrinogen - metabolism Hypercholesterolemia - genetics Hypercholesterolemia - immunology Hypercholesterolemia - pathology Lipopolysaccharides - pharmacology Macrophages, Peritoneal - metabolism Macrophages, Peritoneal - pathology Male Medical sciences Mice Mice, Inbred C57BL Mice, Mutant Strains Monocytes - pathology Pharmacology. Drug treatments T-Lymphocytes - pathology Toxicity: blood Tumor Necrosis Factor-alpha - metabolism Vasculitis - genetics Vasculitis - immunology Vasculitis - pathology |
| title | Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice |
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