Genetic Evidence Supporting a Critical Role of Endothelial Caveolin-1 during the Progression of Atherosclerosis
The accumulation of LDL-derived cholesterol in the artery wall is the initiating event that causes atherosclerosis. However, the mechanisms that lead to the initiation of atherosclerosis are still poorly understood. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene...
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| Veröffentlicht in: | Cell metabolism 2009-07, Vol.10 (1), p.48-54 |
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| creator | Fernández-Hernando, Carlos Yu, Jun Suárez, Yajaira Rahner, Christoph Dávalos, Alberto Lasunción, Miguel A. Sessa, William C. |
| description | The accumulation of LDL-derived cholesterol in the artery wall is the initiating event that causes atherosclerosis. However, the mechanisms that lead to the initiation of atherosclerosis are still poorly understood. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in promoting atherogenesis. Mice were generated lacking Cav-1 and apoE but expressing endothelial-specific Cav-1 in the double knockout background. Genetic ablation of
Cav-1 on an
apoE knockout background inhibits the progression of atherosclerosis, while re-expression of Cav-1 in the endothelium promotes lesion expansion. Mechanistically, the loss of Cav-1 reduces LDL infiltration into the artery wall, promotes nitric oxide production, and reduces the expression of leukocyte adhesion molecules, effects completely reversed in transgenic mice. In summary, this unique model provides physiological evidence supporting the important role of endothelial Cav-1 expression in regulating the entry of LDL into the vessel wall and the initiation of atherosclerosis. |
| doi_str_mv | 10.1016/j.cmet.2009.06.003 |
| format | Article |
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Cav-1 on an
apoE knockout background inhibits the progression of atherosclerosis, while re-expression of Cav-1 in the endothelium promotes lesion expansion. Mechanistically, the loss of Cav-1 reduces LDL infiltration into the artery wall, promotes nitric oxide production, and reduces the expression of leukocyte adhesion molecules, effects completely reversed in transgenic mice. In summary, this unique model provides physiological evidence supporting the important role of endothelial Cav-1 expression in regulating the entry of LDL into the vessel wall and the initiation of atherosclerosis.</description><identifier>ISSN: 1550-4131</identifier><identifier>ISSN: 1932-7420</identifier><identifier>EISSN: 1932-7420</identifier><identifier>DOI: 10.1016/j.cmet.2009.06.003</identifier><identifier>PMID: 19583953</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Apolipoprotein E ; Apolipoproteins E - deficiency ; Apolipoproteins E - genetics ; Apolipoproteins E - metabolism ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; Caveolin 1 - deficiency ; Caveolin 1 - genetics ; Caveolin 1 - metabolism ; Cholesterol, LDL - metabolism ; Disease Progression ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - pathology ; HUMDISEASE ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Nitric Oxide - metabolism</subject><ispartof>Cell metabolism, 2009-07, Vol.10 (1), p.48-54</ispartof><rights>2009 Elsevier Inc.</rights><rights>2009 Elsevier Inc. All rights reserved. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c550t-eb1d07f76bc62ee19222d28a911b6094c4b1a3f03d58e5f4d35fa098e34570e3</citedby><cites>FETCH-LOGICAL-c550t-eb1d07f76bc62ee19222d28a911b6094c4b1a3f03d58e5f4d35fa098e34570e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cmet.2009.06.003$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19583953$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fernández-Hernando, Carlos</creatorcontrib><creatorcontrib>Yu, Jun</creatorcontrib><creatorcontrib>Suárez, Yajaira</creatorcontrib><creatorcontrib>Rahner, Christoph</creatorcontrib><creatorcontrib>Dávalos, Alberto</creatorcontrib><creatorcontrib>Lasunción, Miguel A.</creatorcontrib><creatorcontrib>Sessa, William C.</creatorcontrib><title>Genetic Evidence Supporting a Critical Role of Endothelial Caveolin-1 during the Progression of Atherosclerosis</title><title>Cell metabolism</title><addtitle>Cell Metab</addtitle><description>The accumulation of LDL-derived cholesterol in the artery wall is the initiating event that causes atherosclerosis. However, the mechanisms that lead to the initiation of atherosclerosis are still poorly understood. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in promoting atherogenesis. Mice were generated lacking Cav-1 and apoE but expressing endothelial-specific Cav-1 in the double knockout background. Genetic ablation of
Cav-1 on an
apoE knockout background inhibits the progression of atherosclerosis, while re-expression of Cav-1 in the endothelium promotes lesion expansion. Mechanistically, the loss of Cav-1 reduces LDL infiltration into the artery wall, promotes nitric oxide production, and reduces the expression of leukocyte adhesion molecules, effects completely reversed in transgenic mice. In summary, this unique model provides physiological evidence supporting the important role of endothelial Cav-1 expression in regulating the entry of LDL into the vessel wall and the initiation of atherosclerosis.</description><subject>Animals</subject><subject>Apolipoprotein E</subject><subject>Apolipoproteins E - deficiency</subject><subject>Apolipoproteins E - genetics</subject><subject>Apolipoproteins E - metabolism</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - pathology</subject><subject>Caveolin 1 - deficiency</subject><subject>Caveolin 1 - genetics</subject><subject>Caveolin 1 - metabolism</subject><subject>Cholesterol, LDL - metabolism</subject><subject>Disease Progression</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endothelium, Vascular - pathology</subject><subject>HUMDISEASE</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Nitric Oxide - metabolism</subject><issn>1550-4131</issn><issn>1932-7420</issn><issn>1932-7420</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuLFDEUhYMoztj6B1xIrdxVmXd1QIShaUdhQNHZh1RyqydNOmmTqob596boxsdGN0m495zDzf0Qek1wRzCR7_adPcDUUYxVh2WHMXuCrolitO05xU_rWwjccsLIFXpRyr4KJFPsOboiSqyZEuwapVuIMHnbbE_eQbTQfJ-Px5QnH3eNaTbZ16YJzbcUoEljs40uTQ8QfK1tzAlS8LEljZvzYqid5mtOuwyl-BQXw02t5VRsWE5fXqJnowkFXl3uFbr_uL3ffGrvvtx-3tzctbbOPLUwEIf7sZeDlRSAKEqpo2ujCBkkVtzygRg2YubEGsTIHROjwWoNjIseA1uhD-fY4zwcwFmIUzZBH7M_mPyok_H67070D3qXTpr2TBDS14C3l4CcfsxQJn3wxUIIJkKai5Y9l4Rx9l8hxYRTWiGsED0LbV1EyTD-moZgvfDUe73w1AtPjaWuuKrpzZ__-G25AKyC92cB1GWePGRdrF84Op_BTtol_6_8n0FZs6c</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>Fernández-Hernando, Carlos</creator><creator>Yu, Jun</creator><creator>Suárez, Yajaira</creator><creator>Rahner, Christoph</creator><creator>Dávalos, Alberto</creator><creator>Lasunción, Miguel A.</creator><creator>Sessa, William C.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090701</creationdate><title>Genetic Evidence Supporting a Critical Role of Endothelial Caveolin-1 during the Progression of Atherosclerosis</title><author>Fernández-Hernando, Carlos ; Yu, Jun ; Suárez, Yajaira ; Rahner, Christoph ; Dávalos, Alberto ; Lasunción, Miguel A. ; Sessa, William C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c550t-eb1d07f76bc62ee19222d28a911b6094c4b1a3f03d58e5f4d35fa098e34570e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Apolipoprotein E</topic><topic>Apolipoproteins E - deficiency</topic><topic>Apolipoproteins E - genetics</topic><topic>Apolipoproteins E - metabolism</topic><topic>Atherosclerosis - metabolism</topic><topic>Atherosclerosis - pathology</topic><topic>Caveolin 1 - deficiency</topic><topic>Caveolin 1 - genetics</topic><topic>Caveolin 1 - metabolism</topic><topic>Cholesterol, LDL - metabolism</topic><topic>Disease Progression</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Endothelium, Vascular - pathology</topic><topic>HUMDISEASE</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Nitric Oxide - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fernández-Hernando, Carlos</creatorcontrib><creatorcontrib>Yu, Jun</creatorcontrib><creatorcontrib>Suárez, Yajaira</creatorcontrib><creatorcontrib>Rahner, Christoph</creatorcontrib><creatorcontrib>Dávalos, Alberto</creatorcontrib><creatorcontrib>Lasunción, Miguel A.</creatorcontrib><creatorcontrib>Sessa, William C.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fernández-Hernando, Carlos</au><au>Yu, Jun</au><au>Suárez, Yajaira</au><au>Rahner, Christoph</au><au>Dávalos, Alberto</au><au>Lasunción, Miguel A.</au><au>Sessa, William C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Evidence Supporting a Critical Role of Endothelial Caveolin-1 during the Progression of Atherosclerosis</atitle><jtitle>Cell metabolism</jtitle><addtitle>Cell Metab</addtitle><date>2009-07-01</date><risdate>2009</risdate><volume>10</volume><issue>1</issue><spage>48</spage><epage>54</epage><pages>48-54</pages><issn>1550-4131</issn><issn>1932-7420</issn><eissn>1932-7420</eissn><abstract>The accumulation of LDL-derived cholesterol in the artery wall is the initiating event that causes atherosclerosis. 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Cav-1 on an
apoE knockout background inhibits the progression of atherosclerosis, while re-expression of Cav-1 in the endothelium promotes lesion expansion. Mechanistically, the loss of Cav-1 reduces LDL infiltration into the artery wall, promotes nitric oxide production, and reduces the expression of leukocyte adhesion molecules, effects completely reversed in transgenic mice. In summary, this unique model provides physiological evidence supporting the important role of endothelial Cav-1 expression in regulating the entry of LDL into the vessel wall and the initiation of atherosclerosis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19583953</pmid><doi>10.1016/j.cmet.2009.06.003</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Apolipoprotein E Apolipoproteins E - deficiency Apolipoproteins E - genetics Apolipoproteins E - metabolism Atherosclerosis - metabolism Atherosclerosis - pathology Caveolin 1 - deficiency Caveolin 1 - genetics Caveolin 1 - metabolism Cholesterol, LDL - metabolism Disease Progression Endothelium, Vascular - metabolism Endothelium, Vascular - pathology HUMDISEASE Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Nitric Oxide - metabolism |
| title | Genetic Evidence Supporting a Critical Role of Endothelial Caveolin-1 during the Progression of Atherosclerosis |
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