Plaque-associated endothelial dysfunction in apolipoprotein E-deficient mice on a regular diet. Effect of human apolipoprotein AI
Apolipoprotein E-deficient mice (apoE(-/-)) on a regular diet become hypercholesterolemic and develop atherosclerosis, but endothelium-dependent relaxation remains undisturbed for up to 6 months. We investigated whether vasomotor dysfunction develops in aged apoE(-/-), whether the defect was systemi...
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| Veröffentlicht in: | Cardiovascular research 2003-07, Vol.59 (1), p.189-199 |
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| creator | CRAUWELS, Herta M VAN HOVE, Cor E HOLVOET, Paul HERMAN, Arnold G BULT, Hidde |
| description | Apolipoprotein E-deficient mice (apoE(-/-)) on a regular diet become hypercholesterolemic and develop atherosclerosis, but endothelium-dependent relaxation remains undisturbed for up to 6 months. We investigated whether vasomotor dysfunction develops in aged apoE(-/-), whether the defect was systemic (hypercholesterolemia-dependent) or focal (plaque-related), and the effect of human apolipoprotein AI transgenesis (apoAI/E(-/-)).
Arteries of apoE(-/-) (n=5), apoAI/E(-/-) (n=6) and C57Bl/6J (WT, n=4) mice (18 months) were systematically dissected for isometric tension recording and subsequent morphometry.
Acetylcholine (ACh)-induced relaxation was impaired (P |
| doi_str_mv | 10.1016/S0008-6363(03)00353-5 |
| format | Article |
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Arteries of apoE(-/-) (n=5), apoAI/E(-/-) (n=6) and C57Bl/6J (WT, n=4) mice (18 months) were systematically dissected for isometric tension recording and subsequent morphometry.
Acetylcholine (ACh)-induced relaxation was impaired (P<0.01) in atherosclerotic segments of apoE(-/-) (26+/-14%) as compared to WT mice (93+/-2%). Similar reduced (P<0.01) responses to adenosine 5'-triphosphate (apoE(-/-) 38+/-14, WT 94+/-3%) and the calcium ionophore A23187 (apoE(-/-) 19+/-6%, WT 97+/-2%) pointed to a post-receptor defect. Indeed, responses to exogenous nitric oxide were impaired in atherosclerotic segments as well (apoE(-/-) 71+/-7%, WT 92+/-1%, P<0.05). Furthermore, relaxations inversely correlated with plaque size (ACh r(s)=-0.74, P<0.01). In adjacent plaque-free segments however, responses to ACh (apoE(-/-) 92+/-3%, WT 97+/-1%) and all other agents were preserved, despite the prolonged hypercholesterolemia. ApoAI improved vasomotor responses in atherosclerotic segments. However, negative correlations between maximal relaxation and plaque area remained in apoAI/E(-/-) mice (ACh r(s)=-0.67, P<0.01). Indeed, covariate analysis of variance did not point to direct protection of vasomotor function by apoAI when the smaller lesions were taken into account.
Endothelial dysfunction in apoE(-/-) mice is not affected by hypercholesterolemia alone, but is strictly associated with plaque formation. Human apoAI transgenesis-known to raise HDL-attenuated atherogenesis, thereby indirectly improving relaxation responses in apoE(-/-) mice.</description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1016/S0008-6363(03)00353-5</identifier><identifier>PMID: 12829190</identifier><identifier>CODEN: CVREAU</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Aorta, Thoracic ; Apolipoprotein A-I - genetics ; Apolipoproteins E - deficiency ; Arteriosclerosis - metabolism ; Arteriosclerosis - pathology ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Carotid Arteries ; Cholesterol - blood ; Dose-Response Relationship, Drug ; Endothelium, Vascular - metabolism ; Humans ; Hypolipoproteinemias - metabolism ; Hypolipoproteinemias - pathology ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Phenylephrine - pharmacology ; Vasoconstrictor Agents - pharmacology</subject><ispartof>Cardiovascular research, 2003-07, Vol.59 (1), p.189-199</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-a7d2b37b9cfdf65cdafec77c005c7d9b1f34a8d7e07c27d36803a1a147ca3e153</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14941083$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12829190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CRAUWELS, Herta M</creatorcontrib><creatorcontrib>VAN HOVE, Cor E</creatorcontrib><creatorcontrib>HOLVOET, Paul</creatorcontrib><creatorcontrib>HERMAN, Arnold G</creatorcontrib><creatorcontrib>BULT, Hidde</creatorcontrib><title>Plaque-associated endothelial dysfunction in apolipoprotein E-deficient mice on a regular diet. Effect of human apolipoprotein AI</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>Apolipoprotein E-deficient mice (apoE(-/-)) on a regular diet become hypercholesterolemic and develop atherosclerosis, but endothelium-dependent relaxation remains undisturbed for up to 6 months. We investigated whether vasomotor dysfunction develops in aged apoE(-/-), whether the defect was systemic (hypercholesterolemia-dependent) or focal (plaque-related), and the effect of human apolipoprotein AI transgenesis (apoAI/E(-/-)).
Arteries of apoE(-/-) (n=5), apoAI/E(-/-) (n=6) and C57Bl/6J (WT, n=4) mice (18 months) were systematically dissected for isometric tension recording and subsequent morphometry.
Acetylcholine (ACh)-induced relaxation was impaired (P<0.01) in atherosclerotic segments of apoE(-/-) (26+/-14%) as compared to WT mice (93+/-2%). Similar reduced (P<0.01) responses to adenosine 5'-triphosphate (apoE(-/-) 38+/-14, WT 94+/-3%) and the calcium ionophore A23187 (apoE(-/-) 19+/-6%, WT 97+/-2%) pointed to a post-receptor defect. Indeed, responses to exogenous nitric oxide were impaired in atherosclerotic segments as well (apoE(-/-) 71+/-7%, WT 92+/-1%, P<0.05). Furthermore, relaxations inversely correlated with plaque size (ACh r(s)=-0.74, P<0.01). In adjacent plaque-free segments however, responses to ACh (apoE(-/-) 92+/-3%, WT 97+/-1%) and all other agents were preserved, despite the prolonged hypercholesterolemia. ApoAI improved vasomotor responses in atherosclerotic segments. However, negative correlations between maximal relaxation and plaque area remained in apoAI/E(-/-) mice (ACh r(s)=-0.67, P<0.01). Indeed, covariate analysis of variance did not point to direct protection of vasomotor function by apoAI when the smaller lesions were taken into account.
Endothelial dysfunction in apoE(-/-) mice is not affected by hypercholesterolemia alone, but is strictly associated with plaque formation. Human apoAI transgenesis-known to raise HDL-attenuated atherogenesis, thereby indirectly improving relaxation responses in apoE(-/-) mice.</description><subject>Animals</subject><subject>Aorta, Thoracic</subject><subject>Apolipoprotein A-I - genetics</subject><subject>Apolipoproteins E - deficiency</subject><subject>Arteriosclerosis - metabolism</subject><subject>Arteriosclerosis - pathology</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Carotid Arteries</subject><subject>Cholesterol - blood</subject><subject>Dose-Response Relationship, Drug</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Humans</subject><subject>Hypolipoproteinemias - metabolism</subject><subject>Hypolipoproteinemias - pathology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Phenylephrine - pharmacology</subject><subject>Vasoconstrictor Agents - pharmacology</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNplkMFKHTEUhoO06K31EZRsWtrF2GSSTGaWItdWECrYrsO5yYmmZCbXSWbhsm9url7qohAIB77z_5yPkFPOzjnj3bc7xljfdKITX5j4yphQolEHZMW1Uo1opXpHVv-QI_Ih5z91VErLQ3LE274d-MBW5O9thMcFG8g52QAFHcXJpfKAMUCk7in7ZbIlpImGicI2xbBN2zkVrOO6ceiDDTgVOgaLtFJAZ7xfIszUBSzndO092kKTpw_LCP9FXFx_JO89xIwn-_-Y_L5a_7r80dz8_H59eXHTWClkaUC7diP0ZrDe-U5ZBzVXa1tvstoNG-6FhN5pZNq22omuZwI4cKktCORKHJPPr7m1ul6cixlDthgjTJiWbLSQvO3avoLqFbRzynlGb7ZzGGF-MpyZnXvz4t7sxBpW38692RWc7QuWzYjubWsvuwKf9gBkC9HPMNmQ3zg5SM56IZ4BR7iPFg</recordid><startdate>20030701</startdate><enddate>20030701</enddate><creator>CRAUWELS, Herta M</creator><creator>VAN HOVE, Cor E</creator><creator>HOLVOET, Paul</creator><creator>HERMAN, Arnold G</creator><creator>BULT, Hidde</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20030701</creationdate><title>Plaque-associated endothelial dysfunction in apolipoprotein E-deficient mice on a regular diet. Effect of human apolipoprotein AI</title><author>CRAUWELS, Herta M ; VAN HOVE, Cor E ; HOLVOET, Paul ; HERMAN, Arnold G ; BULT, Hidde</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-a7d2b37b9cfdf65cdafec77c005c7d9b1f34a8d7e07c27d36803a1a147ca3e153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Aorta, Thoracic</topic><topic>Apolipoprotein A-I - genetics</topic><topic>Apolipoproteins E - deficiency</topic><topic>Arteriosclerosis - metabolism</topic><topic>Arteriosclerosis - pathology</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Carotid Arteries</topic><topic>Cholesterol - blood</topic><topic>Dose-Response Relationship, Drug</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Humans</topic><topic>Hypolipoproteinemias - metabolism</topic><topic>Hypolipoproteinemias - pathology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Phenylephrine - pharmacology</topic><topic>Vasoconstrictor Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CRAUWELS, Herta M</creatorcontrib><creatorcontrib>VAN HOVE, Cor E</creatorcontrib><creatorcontrib>HOLVOET, Paul</creatorcontrib><creatorcontrib>HERMAN, Arnold G</creatorcontrib><creatorcontrib>BULT, Hidde</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CRAUWELS, Herta M</au><au>VAN HOVE, Cor E</au><au>HOLVOET, Paul</au><au>HERMAN, Arnold G</au><au>BULT, Hidde</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plaque-associated endothelial dysfunction in apolipoprotein E-deficient mice on a regular diet. Effect of human apolipoprotein AI</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2003-07-01</date><risdate>2003</risdate><volume>59</volume><issue>1</issue><spage>189</spage><epage>199</epage><pages>189-199</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><coden>CVREAU</coden><abstract>Apolipoprotein E-deficient mice (apoE(-/-)) on a regular diet become hypercholesterolemic and develop atherosclerosis, but endothelium-dependent relaxation remains undisturbed for up to 6 months. We investigated whether vasomotor dysfunction develops in aged apoE(-/-), whether the defect was systemic (hypercholesterolemia-dependent) or focal (plaque-related), and the effect of human apolipoprotein AI transgenesis (apoAI/E(-/-)).
Arteries of apoE(-/-) (n=5), apoAI/E(-/-) (n=6) and C57Bl/6J (WT, n=4) mice (18 months) were systematically dissected for isometric tension recording and subsequent morphometry.
Acetylcholine (ACh)-induced relaxation was impaired (P<0.01) in atherosclerotic segments of apoE(-/-) (26+/-14%) as compared to WT mice (93+/-2%). Similar reduced (P<0.01) responses to adenosine 5'-triphosphate (apoE(-/-) 38+/-14, WT 94+/-3%) and the calcium ionophore A23187 (apoE(-/-) 19+/-6%, WT 97+/-2%) pointed to a post-receptor defect. Indeed, responses to exogenous nitric oxide were impaired in atherosclerotic segments as well (apoE(-/-) 71+/-7%, WT 92+/-1%, P<0.05). Furthermore, relaxations inversely correlated with plaque size (ACh r(s)=-0.74, P<0.01). In adjacent plaque-free segments however, responses to ACh (apoE(-/-) 92+/-3%, WT 97+/-1%) and all other agents were preserved, despite the prolonged hypercholesterolemia. ApoAI improved vasomotor responses in atherosclerotic segments. However, negative correlations between maximal relaxation and plaque area remained in apoAI/E(-/-) mice (ACh r(s)=-0.67, P<0.01). Indeed, covariate analysis of variance did not point to direct protection of vasomotor function by apoAI when the smaller lesions were taken into account.
Endothelial dysfunction in apoE(-/-) mice is not affected by hypercholesterolemia alone, but is strictly associated with plaque formation. Human apoAI transgenesis-known to raise HDL-attenuated atherogenesis, thereby indirectly improving relaxation responses in apoE(-/-) mice.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>12829190</pmid><doi>10.1016/S0008-6363(03)00353-5</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Aorta, Thoracic Apolipoprotein A-I - genetics Apolipoproteins E - deficiency Arteriosclerosis - metabolism Arteriosclerosis - pathology Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Carotid Arteries Cholesterol - blood Dose-Response Relationship, Drug Endothelium, Vascular - metabolism Humans Hypolipoproteinemias - metabolism Hypolipoproteinemias - pathology Medical sciences Mice Mice, Inbred C57BL Mice, Transgenic Phenylephrine - pharmacology Vasoconstrictor Agents - pharmacology |
| title | Plaque-associated endothelial dysfunction in apolipoprotein E-deficient mice on a regular diet. Effect of human apolipoprotein AI |
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