Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization
Vascular smooth muscle cells (VSMCs) at capacitance arteries of hypertensive individuals and animals undergo marked age- and blood pressure-dependent polyploidization and hypertrophy. We show here that VSMCs at capacitance arteries of rat models of hypertension display high levels of Akt1/PKB protei...
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| Veröffentlicht in: | The Journal of clinical investigation 2000-10, Vol.106 (8), p.1011-1020 |
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| container_title | The Journal of clinical investigation |
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| creator | Hixon, M L Muro-Cacho, C Wagner, M W Obejero-Paz, C Millie, E Fujio, Y Kureishi, Y Hassold, T Walsh, K Gualberto, A |
| description | Vascular smooth muscle cells (VSMCs) at capacitance arteries of hypertensive individuals and animals undergo marked age- and blood pressure-dependent polyploidization and hypertrophy. We show here that VSMCs at capacitance arteries of rat models of hypertension display high levels of Akt1/PKB protein and activity. Gene transfer of Akt1 to VSMCs isolated from a normotensive rat strain was sufficient to abrogate the activity of the mitotic spindle cell-cycle checkpoint, promoting polyploidization and hypertrophy. Furthermore, the hypertrophic agent angiotensin II induced VSMC polyploidization in an Akt1-dependent manner. These results demonstrate that Akt1 regulates ploidy levels in VSMCs and contributes to vascular smooth muscle polyploidization and hypertrophy during hypertension. |
| doi_str_mv | 10.1172/JCI8252 |
| format | Article |
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We show here that VSMCs at capacitance arteries of rat models of hypertension display high levels of Akt1/PKB protein and activity. Gene transfer of Akt1 to VSMCs isolated from a normotensive rat strain was sufficient to abrogate the activity of the mitotic spindle cell-cycle checkpoint, promoting polyploidization and hypertrophy. Furthermore, the hypertrophic agent angiotensin II induced VSMC polyploidization in an Akt1-dependent manner. These results demonstrate that Akt1 regulates ploidy levels in VSMCs and contributes to vascular smooth muscle polyploidization and hypertrophy during hypertension.</description><identifier>ISSN: 0021-9738</identifier><identifier>DOI: 10.1172/JCI8252</identifier><identifier>PMID: 11032861</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Angiotensin II - pharmacology ; Animals ; Aorta - pathology ; Hypertension - genetics ; Hypertension - pathology ; Hypertrophy ; Mesenteric Arteries - pathology ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - pathology ; Mutagens - pharmacology ; Polyploidy ; Protein-Serine-Threonine Kinases - biosynthesis ; Protein-Serine-Threonine Kinases - genetics ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-akt ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Rats, Zucker ; Recombinant Proteins - biosynthesis ; Up-Regulation</subject><ispartof>The Journal of clinical investigation, 2000-10, Vol.106 (8), p.1011-1020</ispartof><rights>Copyright © 2000, American Society for Clinical Investigation 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c364t-3aa2390c25c198e9154b9dfea176465183d9156494c7ebb10dc177708d49b92b3</citedby><cites>FETCH-LOGICAL-c364t-3aa2390c25c198e9154b9dfea176465183d9156494c7ebb10dc177708d49b92b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC314338/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC314338/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11032861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hixon, M L</creatorcontrib><creatorcontrib>Muro-Cacho, C</creatorcontrib><creatorcontrib>Wagner, M W</creatorcontrib><creatorcontrib>Obejero-Paz, C</creatorcontrib><creatorcontrib>Millie, E</creatorcontrib><creatorcontrib>Fujio, Y</creatorcontrib><creatorcontrib>Kureishi, Y</creatorcontrib><creatorcontrib>Hassold, T</creatorcontrib><creatorcontrib>Walsh, K</creatorcontrib><creatorcontrib>Gualberto, A</creatorcontrib><title>Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Vascular smooth muscle cells (VSMCs) at capacitance arteries of hypertensive individuals and animals undergo marked age- and blood pressure-dependent polyploidization and hypertrophy. We show here that VSMCs at capacitance arteries of rat models of hypertension display high levels of Akt1/PKB protein and activity. Gene transfer of Akt1 to VSMCs isolated from a normotensive rat strain was sufficient to abrogate the activity of the mitotic spindle cell-cycle checkpoint, promoting polyploidization and hypertrophy. Furthermore, the hypertrophic agent angiotensin II induced VSMC polyploidization in an Akt1-dependent manner. These results demonstrate that Akt1 regulates ploidy levels in VSMCs and contributes to vascular smooth muscle polyploidization and hypertrophy during hypertension.</description><subject>Angiotensin II - pharmacology</subject><subject>Animals</subject><subject>Aorta - pathology</subject><subject>Hypertension - genetics</subject><subject>Hypertension - pathology</subject><subject>Hypertrophy</subject><subject>Mesenteric Arteries - pathology</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Mutagens - pharmacology</subject><subject>Polyploidy</subject><subject>Protein-Serine-Threonine Kinases - biosynthesis</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Proto-Oncogene Proteins</subject><subject>Proto-Oncogene Proteins c-akt</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Rats, Inbred WKY</subject><subject>Rats, Zucker</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Up-Regulation</subject><issn>0021-9738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkLtOwzAUhj2AaCmIN0DemEp9bOfigQEqLoVKMMDEEDm22wScOLKTSuHpCbTiMh3pP_9F-hA6AXIOkNDZ_XyR0ojuoTEhFKYiYekIHYbwRghwHvEDNAIgjKYxjNHr5XsLs6eHK9w13qw7K9vS1dgaqQNuHd7IoAbR41A51xa46oKyBitjLS76xvjWu6bosaw1bpztG-tKXX58txyh_ZW0wRzv7gS93Fw_z--my8fbxfxyOVUs5u2USUmZIIpGCkRqBEQ8F3plJCQxjyNImR60mAuuEpPnQLSCJElIqrnIBc3ZBF1se5sur4xWpm69tFnjy0r6PnOyzP5_6rLI1m6TMeCMpUP-bJtX3oXgzeonCiT7QprtkA7O079Lv74dT_YJGud1HQ</recordid><startdate>20001001</startdate><enddate>20001001</enddate><creator>Hixon, M L</creator><creator>Muro-Cacho, C</creator><creator>Wagner, M W</creator><creator>Obejero-Paz, C</creator><creator>Millie, E</creator><creator>Fujio, Y</creator><creator>Kureishi, Y</creator><creator>Hassold, T</creator><creator>Walsh, K</creator><creator>Gualberto, A</creator><general>American Society for Clinical Investigation</general><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>5PM</scope></search><sort><creationdate>20001001</creationdate><title>Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization</title><author>Hixon, M L ; Muro-Cacho, C ; Wagner, M W ; Obejero-Paz, C ; Millie, E ; Fujio, Y ; Kureishi, Y ; Hassold, T ; Walsh, K ; Gualberto, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c364t-3aa2390c25c198e9154b9dfea176465183d9156494c7ebb10dc177708d49b92b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Angiotensin II - pharmacology</topic><topic>Animals</topic><topic>Aorta - pathology</topic><topic>Hypertension - genetics</topic><topic>Hypertension - pathology</topic><topic>Hypertrophy</topic><topic>Mesenteric Arteries - pathology</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscle, Smooth, Vascular - pathology</topic><topic>Mutagens - pharmacology</topic><topic>Polyploidy</topic><topic>Protein-Serine-Threonine Kinases - biosynthesis</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Proto-Oncogene Proteins</topic><topic>Proto-Oncogene Proteins c-akt</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Rats, Inbred WKY</topic><topic>Rats, Zucker</topic><topic>Recombinant Proteins - biosynthesis</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hixon, M L</creatorcontrib><creatorcontrib>Muro-Cacho, C</creatorcontrib><creatorcontrib>Wagner, M W</creatorcontrib><creatorcontrib>Obejero-Paz, C</creatorcontrib><creatorcontrib>Millie, E</creatorcontrib><creatorcontrib>Fujio, Y</creatorcontrib><creatorcontrib>Kureishi, Y</creatorcontrib><creatorcontrib>Hassold, T</creatorcontrib><creatorcontrib>Walsh, K</creatorcontrib><creatorcontrib>Gualberto, A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hixon, M L</au><au>Muro-Cacho, C</au><au>Wagner, M W</au><au>Obejero-Paz, C</au><au>Millie, E</au><au>Fujio, Y</au><au>Kureishi, Y</au><au>Hassold, T</au><au>Walsh, K</au><au>Gualberto, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2000-10-01</date><risdate>2000</risdate><volume>106</volume><issue>8</issue><spage>1011</spage><epage>1020</epage><pages>1011-1020</pages><issn>0021-9738</issn><abstract>Vascular smooth muscle cells (VSMCs) at capacitance arteries of hypertensive individuals and animals undergo marked age- and blood pressure-dependent polyploidization and hypertrophy. We show here that VSMCs at capacitance arteries of rat models of hypertension display high levels of Akt1/PKB protein and activity. Gene transfer of Akt1 to VSMCs isolated from a normotensive rat strain was sufficient to abrogate the activity of the mitotic spindle cell-cycle checkpoint, promoting polyploidization and hypertrophy. Furthermore, the hypertrophic agent angiotensin II induced VSMC polyploidization in an Akt1-dependent manner. These results demonstrate that Akt1 regulates ploidy levels in VSMCs and contributes to vascular smooth muscle polyploidization and hypertrophy during hypertension.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>11032861</pmid><doi>10.1172/JCI8252</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Angiotensin II - pharmacology Animals Aorta - pathology Hypertension - genetics Hypertension - pathology Hypertrophy Mesenteric Arteries - pathology Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - pathology Mutagens - pharmacology Polyploidy Protein-Serine-Threonine Kinases - biosynthesis Protein-Serine-Threonine Kinases - genetics Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Rats Rats, Inbred SHR Rats, Inbred WKY Rats, Zucker Recombinant Proteins - biosynthesis Up-Regulation |
| title | Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization |
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