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Vascular Hypertrophy and Hypertension Caused by Transgenic Overexpression of Profilin 1
We have overexpressed either the cDNA of human profilin 1 or expressed the mutant (88R/L) in the blood vessels of transgenic FVB/N mice. Reverse transcription-PCR indicated selective overexpression of profilin 1 and 88R/L in vascular smooth muscle cells. Polyproline binding showed increased profilin...
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| Published in: | The Journal of biological chemistry 2007-12, Vol.282 (52), p.37632-37639 |
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| creator | Moustafa-Bayoumi, Moustafa Alhaj, Mazin A. El-Sayed, Osama Wisel, Sheik Chotani, Maqsood A. Abouelnaga, Zeinb A. Hassona, Mohamed D.H. Rigatto, Katya Morris, Mariana Nuovo, Gerard Zweier, Jay L. Goldschmidt-Clermont, Pascal Hassanain, Hamdy |
| description | We have overexpressed either the cDNA of human profilin 1 or expressed the mutant (88R/L) in the blood vessels of transgenic FVB/N mice. Reverse transcription-PCR indicated selective overexpression of profilin 1 and 88R/L in vascular smooth muscle cells. Polyproline binding showed increased profilin 1 and 88R/L proteins in transgenic mice compared with control (∼30%, p < 0.05). Rhodamine-phalloidin staining revealed increase stress fiber formation in vascular smooth muscle cells of profilin 1 compared with 88R/L and control. Hematoxylin and eosin staining showed clear signs of vascular hypertrophy in the aorta of profilin 1 mice versus 88R/L and control. However, there were no differences between 88R/L and control mice. Western blotting confirmed the activation of the hypertrophic signaling cascades in aortas of profilin 1 mice. Phospho-ERK1/2 was significantly higher in profilin 1 than 88R/L and control (512.3 and 361.7%, respectively, p < 0.05). Profilin 1 mice had significant increases in phospho-JNK as compared with 88R/L and control (371.4 and 346%, respectively, p < 0.05). However, there were no differences between 88R/L and control mice in both kinases. There was a significant increase in ROCK II kinase in the aorta of profilin 1 mice compared with controls (>400%, p < 0.05). Tail cuff and circadian monitoring of blood pressure showed significant increases in systolic and mean arterial blood pressures of profilin 1 mice starting at age 6 months compared with controls (∼25 mm Hg, p < 0.05). These results suggest that increased actin polymerization in blood vessels triggers activation of the hypertrophic signaling cascades and results in elevation of blood pressure at advanced age. |
| doi_str_mv | 10.1074/jbc.M703227200 |
| format | article |
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Reverse transcription-PCR indicated selective overexpression of profilin 1 and 88R/L in vascular smooth muscle cells. Polyproline binding showed increased profilin 1 and 88R/L proteins in transgenic mice compared with control (∼30%, p < 0.05). Rhodamine-phalloidin staining revealed increase stress fiber formation in vascular smooth muscle cells of profilin 1 compared with 88R/L and control. Hematoxylin and eosin staining showed clear signs of vascular hypertrophy in the aorta of profilin 1 mice versus 88R/L and control. However, there were no differences between 88R/L and control mice. Western blotting confirmed the activation of the hypertrophic signaling cascades in aortas of profilin 1 mice. Phospho-ERK1/2 was significantly higher in profilin 1 than 88R/L and control (512.3 and 361.7%, respectively, p < 0.05). Profilin 1 mice had significant increases in phospho-JNK as compared with 88R/L and control (371.4 and 346%, respectively, p < 0.05). However, there were no differences between 88R/L and control mice in both kinases. There was a significant increase in ROCK II kinase in the aorta of profilin 1 mice compared with controls (>400%, p < 0.05). Tail cuff and circadian monitoring of blood pressure showed significant increases in systolic and mean arterial blood pressures of profilin 1 mice starting at age 6 months compared with controls (∼25 mm Hg, p < 0.05). These results suggest that increased actin polymerization in blood vessels triggers activation of the hypertrophic signaling cascades and results in elevation of blood pressure at advanced age.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M703227200</identifier><identifier>PMID: 17942408</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Actins - chemistry ; Animals ; Aorta - metabolism ; Aortic Valve - cytology ; Blood Pressure ; Gene Expression Regulation ; Hypertension - genetics ; Hypertrophy - genetics ; MAP Kinase Signaling System ; Mice ; Mice, Transgenic ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - metabolism ; Models, Biological ; Myocytes, Smooth Muscle - cytology ; Profilins - biosynthesis ; Profilins - genetics ; Signal Transduction</subject><ispartof>The Journal of biological chemistry, 2007-12, Vol.282 (52), p.37632-37639</ispartof><rights>2007 © 2007 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-5173dcd8689cf77493ebb84da150d16e6bfeb4b2ed6f2aadcc9c99b4dcd4120b3</citedby><cites>FETCH-LOGICAL-c396t-5173dcd8689cf77493ebb84da150d16e6bfeb4b2ed6f2aadcc9c99b4dcd4120b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17942408$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moustafa-Bayoumi, Moustafa</creatorcontrib><creatorcontrib>Alhaj, Mazin A.</creatorcontrib><creatorcontrib>El-Sayed, Osama</creatorcontrib><creatorcontrib>Wisel, Sheik</creatorcontrib><creatorcontrib>Chotani, Maqsood A.</creatorcontrib><creatorcontrib>Abouelnaga, Zeinb A.</creatorcontrib><creatorcontrib>Hassona, Mohamed D.H.</creatorcontrib><creatorcontrib>Rigatto, Katya</creatorcontrib><creatorcontrib>Morris, Mariana</creatorcontrib><creatorcontrib>Nuovo, Gerard</creatorcontrib><creatorcontrib>Zweier, Jay L.</creatorcontrib><creatorcontrib>Goldschmidt-Clermont, Pascal</creatorcontrib><creatorcontrib>Hassanain, Hamdy</creatorcontrib><title>Vascular Hypertrophy and Hypertension Caused by Transgenic Overexpression of Profilin 1</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>We have overexpressed either the cDNA of human profilin 1 or expressed the mutant (88R/L) in the blood vessels of transgenic FVB/N mice. Reverse transcription-PCR indicated selective overexpression of profilin 1 and 88R/L in vascular smooth muscle cells. Polyproline binding showed increased profilin 1 and 88R/L proteins in transgenic mice compared with control (∼30%, p < 0.05). Rhodamine-phalloidin staining revealed increase stress fiber formation in vascular smooth muscle cells of profilin 1 compared with 88R/L and control. Hematoxylin and eosin staining showed clear signs of vascular hypertrophy in the aorta of profilin 1 mice versus 88R/L and control. However, there were no differences between 88R/L and control mice. Western blotting confirmed the activation of the hypertrophic signaling cascades in aortas of profilin 1 mice. Phospho-ERK1/2 was significantly higher in profilin 1 than 88R/L and control (512.3 and 361.7%, respectively, p < 0.05). Profilin 1 mice had significant increases in phospho-JNK as compared with 88R/L and control (371.4 and 346%, respectively, p < 0.05). However, there were no differences between 88R/L and control mice in both kinases. There was a significant increase in ROCK II kinase in the aorta of profilin 1 mice compared with controls (>400%, p < 0.05). Tail cuff and circadian monitoring of blood pressure showed significant increases in systolic and mean arterial blood pressures of profilin 1 mice starting at age 6 months compared with controls (∼25 mm Hg, p < 0.05). These results suggest that increased actin polymerization in blood vessels triggers activation of the hypertrophic signaling cascades and results in elevation of blood pressure at advanced age.</description><subject>Actins - chemistry</subject><subject>Animals</subject><subject>Aorta - metabolism</subject><subject>Aortic Valve - cytology</subject><subject>Blood Pressure</subject><subject>Gene Expression Regulation</subject><subject>Hypertension - genetics</subject><subject>Hypertrophy - genetics</subject><subject>MAP Kinase Signaling System</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Models, Biological</subject><subject>Myocytes, Smooth Muscle - cytology</subject><subject>Profilins - biosynthesis</subject><subject>Profilins - genetics</subject><subject>Signal Transduction</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNqF0Etv1DAUBWALgehQ2LKELBC7DNePxPESjaBFKioSLbCz_LiZcZWJp_akdP49LhmpK4Q3lqXvHvkeQl5TWFKQ4sONdcuvEjhjkgE8IQsKHa95Q389JQsARmvFmu6EvMj5BsoRij4nJ1QqwQR0C_Lzh8luGkyqzg87TPsUd5tDZUZ_fOOYQxyrlZky-soeqqtkxrzGMbjq8g4T3u8S5r8m9tW3FPswhLGiL8mz3gwZXx3vU3L9-dPV6ry-uDz7svp4UTuu2n3dUMm9813bKddLKRRHazvhDW3A0xZb26MVlqFve2aMd045pawoM4IysPyUvJ9zdyneTpj3ehuyw2EwI8Yp61ZBRzml_4VUCQkSRIHLGboUc07Y610KW5MOmoJ-6FyXzvVj52XgzTF5slv0j_xYcgHvZrAJ683vkFDbEN0Gt5p1TDdMc9lyVtjbmfUmarNOIevr7wwoh5KhQD3s0M0CS6N3AZPOLuDo0JdQt9c-hn998g_gA6Yc</recordid><startdate>20071228</startdate><enddate>20071228</enddate><creator>Moustafa-Bayoumi, Moustafa</creator><creator>Alhaj, Mazin A.</creator><creator>El-Sayed, Osama</creator><creator>Wisel, Sheik</creator><creator>Chotani, Maqsood A.</creator><creator>Abouelnaga, Zeinb A.</creator><creator>Hassona, Mohamed D.H.</creator><creator>Rigatto, Katya</creator><creator>Morris, Mariana</creator><creator>Nuovo, Gerard</creator><creator>Zweier, Jay L.</creator><creator>Goldschmidt-Clermont, Pascal</creator><creator>Hassanain, Hamdy</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20071228</creationdate><title>Vascular Hypertrophy and Hypertension Caused by Transgenic Overexpression of Profilin 1</title><author>Moustafa-Bayoumi, Moustafa ; Alhaj, Mazin A. ; El-Sayed, Osama ; Wisel, Sheik ; Chotani, Maqsood A. ; Abouelnaga, Zeinb A. ; Hassona, Mohamed D.H. ; Rigatto, Katya ; Morris, Mariana ; Nuovo, Gerard ; Zweier, Jay L. ; Goldschmidt-Clermont, Pascal ; Hassanain, Hamdy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-5173dcd8689cf77493ebb84da150d16e6bfeb4b2ed6f2aadcc9c99b4dcd4120b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Actins - chemistry</topic><topic>Animals</topic><topic>Aorta - metabolism</topic><topic>Aortic Valve - cytology</topic><topic>Blood Pressure</topic><topic>Gene Expression Regulation</topic><topic>Hypertension - genetics</topic><topic>Hypertrophy - genetics</topic><topic>MAP Kinase Signaling System</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Models, Biological</topic><topic>Myocytes, Smooth Muscle - cytology</topic><topic>Profilins - biosynthesis</topic><topic>Profilins - genetics</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moustafa-Bayoumi, Moustafa</creatorcontrib><creatorcontrib>Alhaj, Mazin A.</creatorcontrib><creatorcontrib>El-Sayed, Osama</creatorcontrib><creatorcontrib>Wisel, Sheik</creatorcontrib><creatorcontrib>Chotani, Maqsood A.</creatorcontrib><creatorcontrib>Abouelnaga, Zeinb A.</creatorcontrib><creatorcontrib>Hassona, Mohamed D.H.</creatorcontrib><creatorcontrib>Rigatto, Katya</creatorcontrib><creatorcontrib>Morris, Mariana</creatorcontrib><creatorcontrib>Nuovo, Gerard</creatorcontrib><creatorcontrib>Zweier, Jay L.</creatorcontrib><creatorcontrib>Goldschmidt-Clermont, Pascal</creatorcontrib><creatorcontrib>Hassanain, Hamdy</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</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><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moustafa-Bayoumi, Moustafa</au><au>Alhaj, Mazin A.</au><au>El-Sayed, Osama</au><au>Wisel, Sheik</au><au>Chotani, Maqsood A.</au><au>Abouelnaga, Zeinb A.</au><au>Hassona, Mohamed D.H.</au><au>Rigatto, Katya</au><au>Morris, Mariana</au><au>Nuovo, Gerard</au><au>Zweier, Jay L.</au><au>Goldschmidt-Clermont, Pascal</au><au>Hassanain, Hamdy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vascular Hypertrophy and Hypertension Caused by Transgenic Overexpression of Profilin 1</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2007-12-28</date><risdate>2007</risdate><volume>282</volume><issue>52</issue><spage>37632</spage><epage>37639</epage><pages>37632-37639</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><notes>http://www.jbc.org/</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>We have overexpressed either the cDNA of human profilin 1 or expressed the mutant (88R/L) in the blood vessels of transgenic FVB/N mice. Reverse transcription-PCR indicated selective overexpression of profilin 1 and 88R/L in vascular smooth muscle cells. Polyproline binding showed increased profilin 1 and 88R/L proteins in transgenic mice compared with control (∼30%, p < 0.05). Rhodamine-phalloidin staining revealed increase stress fiber formation in vascular smooth muscle cells of profilin 1 compared with 88R/L and control. Hematoxylin and eosin staining showed clear signs of vascular hypertrophy in the aorta of profilin 1 mice versus 88R/L and control. However, there were no differences between 88R/L and control mice. Western blotting confirmed the activation of the hypertrophic signaling cascades in aortas of profilin 1 mice. Phospho-ERK1/2 was significantly higher in profilin 1 than 88R/L and control (512.3 and 361.7%, respectively, p < 0.05). Profilin 1 mice had significant increases in phospho-JNK as compared with 88R/L and control (371.4 and 346%, respectively, p < 0.05). However, there were no differences between 88R/L and control mice in both kinases. There was a significant increase in ROCK II kinase in the aorta of profilin 1 mice compared with controls (>400%, p < 0.05). Tail cuff and circadian monitoring of blood pressure showed significant increases in systolic and mean arterial blood pressures of profilin 1 mice starting at age 6 months compared with controls (∼25 mm Hg, p < 0.05). These results suggest that increased actin polymerization in blood vessels triggers activation of the hypertrophic signaling cascades and results in elevation of blood pressure at advanced age.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17942408</pmid><doi>10.1074/jbc.M703227200</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actins - chemistry Animals Aorta - metabolism Aortic Valve - cytology Blood Pressure Gene Expression Regulation Hypertension - genetics Hypertrophy - genetics MAP Kinase Signaling System Mice Mice, Transgenic Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism Models, Biological Myocytes, Smooth Muscle - cytology Profilins - biosynthesis Profilins - genetics Signal Transduction |
| title | Vascular Hypertrophy and Hypertension Caused by Transgenic Overexpression of Profilin 1 |
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