Increased level of p63RhoGEF and RhoA/Rho kinase activity in hypertensive patients
OBJECTIVE:p63RhoGEF, a guanine nucleotide exchange factor, has been reported ‘in vitro’ as key mediator of the angiotensin II-induced RhoA/Rho kinase activation leading to vasoconstriction and cardiovascular remodeling. We assessed p63RhoGEF gene and protein expression and RhoA/Rho kinase activity i...
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| Veröffentlicht in: | Journal of hypertension 2014-02, Vol.32 (2), p.331-338 |
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| creator | Calò, Lorenzo A Davis, Paul A Pagnin, Elisa Dal Maso, Lucia Maiolino, Giuseppe M. Seccia, Teresa Pessina, Achille C Rossi, Gian Paolo |
| description | OBJECTIVE:p63RhoGEF, a guanine nucleotide exchange factor, has been reported ‘in vitro’ as key mediator of the angiotensin II-induced RhoA/Rho kinase activation leading to vasoconstriction and cardiovascular remodeling. We assessed p63RhoGEF gene and protein expression and RhoA/Rho kinase activity in essential hypertensive and Bartterʼs and Gitelmanʼs syndrome patients, a human model opposite to hypertension; the latter have, in fact, increased plasma angiotensin II, activation of the renin–angiotensin system, yet normotension/hypotension, reduced peripheral resistance and lack of cardiovascular remodeling due to an endogenously blunted angiotensin II type 1 receptor signaling.
METHODS:Mononuclear cell p63RhoGEF gene and protein expression and the phosphorylation status of the myosin phosphatase target protein-1 (MYPT-1), marker of Rho kinase activity, were assessed in essential hypertensive patients, Bartterʼs/Gitelmanʼs patients and healthy individuals by quantitative real-time PCR and western blot.
RESULTS:p63RhoGEF mRNA and protein level and MYPT-1 phosphorylation status were higher in hypertensive patients and lower in Bartterʼs/Gitelmanʼs patients compared with healthy individualsp63RhoGEF mRNA level0.59 ± 0.17 ΔΔCt vs. 0.37 ± 0.17 vs. 0.20 ± 0.19, analysis of variance (ANOVA)P |
| doi_str_mv | 10.1097/HJH.0000000000000075 |
| format | Article |
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METHODS:Mononuclear cell p63RhoGEF gene and protein expression and the phosphorylation status of the myosin phosphatase target protein-1 (MYPT-1), marker of Rho kinase activity, were assessed in essential hypertensive patients, Bartterʼs/Gitelmanʼs patients and healthy individuals by quantitative real-time PCR and western blot.
RESULTS:p63RhoGEF mRNA and protein level and MYPT-1 phosphorylation status were higher in hypertensive patients and lower in Bartterʼs/Gitelmanʼs patients compared with healthy individualsp63RhoGEF mRNA level0.59 ± 0.17 ΔΔCt vs. 0.37 ± 0.17 vs. 0.20 ± 0.19, analysis of variance (ANOVA)P <0.016; p63RhoGEF protein level 1.35 ± 0.14 vs. 1.09 ± 0.05 vs. 0.90 ± 0.09 densitometric units, ANOVAP <0.0001; MYPT-11.39 ± 0.34 vs. 1.01 ± 0.12 vs. 0.81 ± 0.06, ANOVAP < 0.0001. p63RhoGEF mRNA was significantly correlated with both SBP and DBP in both hypertensive patients (R = 0.79, P < 0.02 and R = 0.78, P < 0.02) and in Bartterʼs syndrome/Gitelmanʼs syndrome patients (R = 0.87, P < 0.001 and R = 0.86, P < 0.001), respectively.
CONCLUSION:Increased p63RhoGEF mRNA and protein level and Rho kinase activity are shown for the first time in essential hypertensive patients, whereas the opposite was found in Bartterʼs/Gitelmanʼs patients, a human model opposite to hypertension. These results combined with other ‘in-vitro’ studies strongly support the crucial importance of p63RhoGEF in Ang II-mediated signaling involved in the regulation of blood pressure and its long-term complications in humans.]]></description><identifier>ISSN: 0263-6352</identifier><identifier>EISSN: 1473-5598</identifier><identifier>DOI: 10.1097/HJH.0000000000000075</identifier><identifier>PMID: 24356540</identifier><language>eng</language><publisher>England: Wolters Kluwer Health | Lippincott Williams & Wilkins</publisher><subject>Adult ; Angiotensin II - physiology ; Bartter Syndrome - blood ; Bartter Syndrome - genetics ; Bartter Syndrome - physiopathology ; Blood Pressure ; Case-Control Studies ; Female ; Gitelman Syndrome - blood ; Gitelman Syndrome - genetics ; Gitelman Syndrome - physiopathology ; Humans ; Hypertension - blood ; Hypertension - genetics ; Hypertension - physiopathology ; Leukocytes, Mononuclear - metabolism ; Male ; Middle Aged ; Myosin-Light-Chain Phosphatase - blood ; Myosin-Light-Chain Phosphatase - chemistry ; Phosphorylation ; Rho Guanine Nucleotide Exchange Factors - blood ; Rho Guanine Nucleotide Exchange Factors - genetics ; rho-Associated Kinases - blood ; rhoA GTP-Binding Protein - blood ; RNA, Messenger - blood ; RNA, Messenger - genetics ; Signal Transduction ; Solute Carrier Family 12, Member 3 - genetics</subject><ispartof>Journal of hypertension, 2014-02, Vol.32 (2), p.331-338</ispartof><rights>2014 Wolters Kluwer Health | Lippincott Williams & Wilkins</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4225-5c691101f2861da7604e5afc5d12f6f4a5ec744bac9b08aa2ad96b89fedba39c3</citedby><cites>FETCH-LOGICAL-c4225-5c691101f2861da7604e5afc5d12f6f4a5ec744bac9b08aa2ad96b89fedba39c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24356540$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Calò, Lorenzo A</creatorcontrib><creatorcontrib>Davis, Paul A</creatorcontrib><creatorcontrib>Pagnin, Elisa</creatorcontrib><creatorcontrib>Dal Maso, Lucia</creatorcontrib><creatorcontrib>Maiolino, Giuseppe</creatorcontrib><creatorcontrib>M. Seccia, Teresa</creatorcontrib><creatorcontrib>Pessina, Achille C</creatorcontrib><creatorcontrib>Rossi, Gian Paolo</creatorcontrib><title>Increased level of p63RhoGEF and RhoA/Rho kinase activity in hypertensive patients</title><title>Journal of hypertension</title><addtitle>J Hypertens</addtitle><description><![CDATA[OBJECTIVE:p63RhoGEF, a guanine nucleotide exchange factor, has been reported ‘in vitro’ as key mediator of the angiotensin II-induced RhoA/Rho kinase activation leading to vasoconstriction and cardiovascular remodeling. We assessed p63RhoGEF gene and protein expression and RhoA/Rho kinase activity in essential hypertensive and Bartterʼs and Gitelmanʼs syndrome patients, a human model opposite to hypertension; the latter have, in fact, increased plasma angiotensin II, activation of the renin–angiotensin system, yet normotension/hypotension, reduced peripheral resistance and lack of cardiovascular remodeling due to an endogenously blunted angiotensin II type 1 receptor signaling.
METHODS:Mononuclear cell p63RhoGEF gene and protein expression and the phosphorylation status of the myosin phosphatase target protein-1 (MYPT-1), marker of Rho kinase activity, were assessed in essential hypertensive patients, Bartterʼs/Gitelmanʼs patients and healthy individuals by quantitative real-time PCR and western blot.
RESULTS:p63RhoGEF mRNA and protein level and MYPT-1 phosphorylation status were higher in hypertensive patients and lower in Bartterʼs/Gitelmanʼs patients compared with healthy individualsp63RhoGEF mRNA level0.59 ± 0.17 ΔΔCt vs. 0.37 ± 0.17 vs. 0.20 ± 0.19, analysis of variance (ANOVA)P <0.016; p63RhoGEF protein level 1.35 ± 0.14 vs. 1.09 ± 0.05 vs. 0.90 ± 0.09 densitometric units, ANOVAP <0.0001; MYPT-11.39 ± 0.34 vs. 1.01 ± 0.12 vs. 0.81 ± 0.06, ANOVAP < 0.0001. p63RhoGEF mRNA was significantly correlated with both SBP and DBP in both hypertensive patients (R = 0.79, P < 0.02 and R = 0.78, P < 0.02) and in Bartterʼs syndrome/Gitelmanʼs syndrome patients (R = 0.87, P < 0.001 and R = 0.86, P < 0.001), respectively.
CONCLUSION:Increased p63RhoGEF mRNA and protein level and Rho kinase activity are shown for the first time in essential hypertensive patients, whereas the opposite was found in Bartterʼs/Gitelmanʼs patients, a human model opposite to hypertension. These results combined with other ‘in-vitro’ studies strongly support the crucial importance of p63RhoGEF in Ang II-mediated signaling involved in the regulation of blood pressure and its long-term complications in humans.]]></description><subject>Adult</subject><subject>Angiotensin II - physiology</subject><subject>Bartter Syndrome - blood</subject><subject>Bartter Syndrome - genetics</subject><subject>Bartter Syndrome - physiopathology</subject><subject>Blood Pressure</subject><subject>Case-Control Studies</subject><subject>Female</subject><subject>Gitelman Syndrome - blood</subject><subject>Gitelman Syndrome - genetics</subject><subject>Gitelman Syndrome - physiopathology</subject><subject>Humans</subject><subject>Hypertension - blood</subject><subject>Hypertension - genetics</subject><subject>Hypertension - physiopathology</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myosin-Light-Chain Phosphatase - blood</subject><subject>Myosin-Light-Chain Phosphatase - chemistry</subject><subject>Phosphorylation</subject><subject>Rho Guanine Nucleotide Exchange Factors - blood</subject><subject>Rho Guanine Nucleotide Exchange Factors - genetics</subject><subject>rho-Associated Kinases - blood</subject><subject>rhoA GTP-Binding Protein - blood</subject><subject>RNA, Messenger - blood</subject><subject>RNA, Messenger - genetics</subject><subject>Signal Transduction</subject><subject>Solute Carrier Family 12, Member 3 - genetics</subject><issn>0263-6352</issn><issn>1473-5598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kN9LwzAQx4Mobk7_A5E8-tItaZO0eRxjv2QgDH0OaXqldV1bk3ay_97IpqAP3sPdPXy-d_BB6J6SMSUynqyeVmPyq2J-gYaUxVHAuUwu0ZCEIgpExMMBunHuzSOJjKNrNAhZxAVnZIi269pY0A4yXMEBKtzkuBXRtmiW8wXWdYb9Op34hndl7TmsTVceyu6IyxoXxxZsB7UrD4Bb3ZVQd-4WXeW6cnB3niP0upi_zFbB5nm5nk03gWFhyANuhKSU0DxMBM10LAgDrnPDMxrmImeag4kZS7WRKUm0DnUmRZrIHLJUR9JEI_R4utva5r0H16l96QxUla6h6Z2iTHolnAjmUXZCjW2cs5Cr1pZ7bY-KEvVlU3mb6q9NH3s4f-jTPWQ_oW99HkhOwEdTdWDdruo_wKoCdNUV_9_-BE6IgIQ</recordid><startdate>201402</startdate><enddate>201402</enddate><creator>Calò, Lorenzo A</creator><creator>Davis, Paul A</creator><creator>Pagnin, Elisa</creator><creator>Dal Maso, Lucia</creator><creator>Maiolino, Giuseppe</creator><creator>M. Seccia, Teresa</creator><creator>Pessina, Achille C</creator><creator>Rossi, Gian Paolo</creator><general>Wolters Kluwer Health | Lippincott Williams & Wilkins</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>7X8</scope></search><sort><creationdate>201402</creationdate><title>Increased level of p63RhoGEF and RhoA/Rho kinase activity in hypertensive patients</title><author>Calò, Lorenzo A ; Davis, Paul A ; Pagnin, Elisa ; Dal Maso, Lucia ; Maiolino, Giuseppe ; M. Seccia, Teresa ; Pessina, Achille C ; Rossi, Gian Paolo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4225-5c691101f2861da7604e5afc5d12f6f4a5ec744bac9b08aa2ad96b89fedba39c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Angiotensin II - physiology</topic><topic>Bartter Syndrome - blood</topic><topic>Bartter Syndrome - genetics</topic><topic>Bartter Syndrome - physiopathology</topic><topic>Blood Pressure</topic><topic>Case-Control Studies</topic><topic>Female</topic><topic>Gitelman Syndrome - blood</topic><topic>Gitelman Syndrome - genetics</topic><topic>Gitelman Syndrome - physiopathology</topic><topic>Humans</topic><topic>Hypertension - blood</topic><topic>Hypertension - genetics</topic><topic>Hypertension - physiopathology</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myosin-Light-Chain Phosphatase - blood</topic><topic>Myosin-Light-Chain Phosphatase - chemistry</topic><topic>Phosphorylation</topic><topic>Rho Guanine Nucleotide Exchange Factors - blood</topic><topic>Rho Guanine Nucleotide Exchange Factors - genetics</topic><topic>rho-Associated Kinases - blood</topic><topic>rhoA GTP-Binding Protein - blood</topic><topic>RNA, Messenger - blood</topic><topic>RNA, Messenger - genetics</topic><topic>Signal Transduction</topic><topic>Solute Carrier Family 12, Member 3 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Calò, Lorenzo A</creatorcontrib><creatorcontrib>Davis, Paul A</creatorcontrib><creatorcontrib>Pagnin, Elisa</creatorcontrib><creatorcontrib>Dal Maso, Lucia</creatorcontrib><creatorcontrib>Maiolino, Giuseppe</creatorcontrib><creatorcontrib>M. Seccia, Teresa</creatorcontrib><creatorcontrib>Pessina, Achille C</creatorcontrib><creatorcontrib>Rossi, Gian Paolo</creatorcontrib><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>Journal of hypertension</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Calò, Lorenzo A</au><au>Davis, Paul A</au><au>Pagnin, Elisa</au><au>Dal Maso, Lucia</au><au>Maiolino, Giuseppe</au><au>M. Seccia, Teresa</au><au>Pessina, Achille C</au><au>Rossi, Gian Paolo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased level of p63RhoGEF and RhoA/Rho kinase activity in hypertensive patients</atitle><jtitle>Journal of hypertension</jtitle><addtitle>J Hypertens</addtitle><date>2014-02</date><risdate>2014</risdate><volume>32</volume><issue>2</issue><spage>331</spage><epage>338</epage><pages>331-338</pages><issn>0263-6352</issn><eissn>1473-5598</eissn><abstract><![CDATA[OBJECTIVE:p63RhoGEF, a guanine nucleotide exchange factor, has been reported ‘in vitro’ as key mediator of the angiotensin II-induced RhoA/Rho kinase activation leading to vasoconstriction and cardiovascular remodeling. We assessed p63RhoGEF gene and protein expression and RhoA/Rho kinase activity in essential hypertensive and Bartterʼs and Gitelmanʼs syndrome patients, a human model opposite to hypertension; the latter have, in fact, increased plasma angiotensin II, activation of the renin–angiotensin system, yet normotension/hypotension, reduced peripheral resistance and lack of cardiovascular remodeling due to an endogenously blunted angiotensin II type 1 receptor signaling.
METHODS:Mononuclear cell p63RhoGEF gene and protein expression and the phosphorylation status of the myosin phosphatase target protein-1 (MYPT-1), marker of Rho kinase activity, were assessed in essential hypertensive patients, Bartterʼs/Gitelmanʼs patients and healthy individuals by quantitative real-time PCR and western blot.
RESULTS:p63RhoGEF mRNA and protein level and MYPT-1 phosphorylation status were higher in hypertensive patients and lower in Bartterʼs/Gitelmanʼs patients compared with healthy individualsp63RhoGEF mRNA level0.59 ± 0.17 ΔΔCt vs. 0.37 ± 0.17 vs. 0.20 ± 0.19, analysis of variance (ANOVA)P <0.016; p63RhoGEF protein level 1.35 ± 0.14 vs. 1.09 ± 0.05 vs. 0.90 ± 0.09 densitometric units, ANOVAP <0.0001; MYPT-11.39 ± 0.34 vs. 1.01 ± 0.12 vs. 0.81 ± 0.06, ANOVAP < 0.0001. p63RhoGEF mRNA was significantly correlated with both SBP and DBP in both hypertensive patients (R = 0.79, P < 0.02 and R = 0.78, P < 0.02) and in Bartterʼs syndrome/Gitelmanʼs syndrome patients (R = 0.87, P < 0.001 and R = 0.86, P < 0.001), respectively.
CONCLUSION:Increased p63RhoGEF mRNA and protein level and Rho kinase activity are shown for the first time in essential hypertensive patients, whereas the opposite was found in Bartterʼs/Gitelmanʼs patients, a human model opposite to hypertension. These results combined with other ‘in-vitro’ studies strongly support the crucial importance of p63RhoGEF in Ang II-mediated signaling involved in the regulation of blood pressure and its long-term complications in humans.]]></abstract><cop>England</cop><pub>Wolters Kluwer Health | Lippincott Williams & Wilkins</pub><pmid>24356540</pmid><doi>10.1097/HJH.0000000000000075</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Angiotensin II - physiology Bartter Syndrome - blood Bartter Syndrome - genetics Bartter Syndrome - physiopathology Blood Pressure Case-Control Studies Female Gitelman Syndrome - blood Gitelman Syndrome - genetics Gitelman Syndrome - physiopathology Humans Hypertension - blood Hypertension - genetics Hypertension - physiopathology Leukocytes, Mononuclear - metabolism Male Middle Aged Myosin-Light-Chain Phosphatase - blood Myosin-Light-Chain Phosphatase - chemistry Phosphorylation Rho Guanine Nucleotide Exchange Factors - blood Rho Guanine Nucleotide Exchange Factors - genetics rho-Associated Kinases - blood rhoA GTP-Binding Protein - blood RNA, Messenger - blood RNA, Messenger - genetics Signal Transduction Solute Carrier Family 12, Member 3 - genetics |
| title | Increased level of p63RhoGEF and RhoA/Rho kinase activity in hypertensive patients |
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