Vasoactive intestinal peptide infusion reverses existing myocardial fibrosis in the rat
Congestive cardiac failure has become one of the major health challenges of the 21st century and new therapies are needed to address this problem. The concentration of vasoactive intestinal peptide (VIP) in the heart has been shown to decrease as fibrosis (the pathology leading to heart failure) inc...
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| Veröffentlicht in: | European journal of pharmacology 2019-11, Vol.862, p.172629-172629, Article 172629 |
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| container_title | European journal of pharmacology |
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| creator | Duggan, Karen A. Hodge, George Chen, Juchuan Hunter, Tegan |
| description | Congestive cardiac failure has become one of the major health challenges of the 21st century and new therapies are needed to address this problem. The concentration of vasoactive intestinal peptide (VIP) in the heart has been shown to decrease as fibrosis (the pathology leading to heart failure) increases and to become undetectable in end stage cardiomyopathy. We sought to determine whether replenishment of myocardial VIP might treat myocardial fibrosis and therefore represent a new therapeutic target.
Wistar Kyoto rats on a high (4.4%) salt diet were randomised to zero time control, 4 week infusion of VIP (5 pmol/kg/min) or vehicle control infusion. Myocardial VIP concentration was measured by radioimmunoassay, fibrosis was quantitated by computerised histomorphometry and changes in pro-fibrotic mediators were measured by quantitative rt-PCR.
Myocardial VIP increased significantly in VIP treated rats compared with vehicle treated controls (P |
| doi_str_mv | 10.1016/j.ejphar.2019.172629 |
| format | Article |
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Wistar Kyoto rats on a high (4.4%) salt diet were randomised to zero time control, 4 week infusion of VIP (5 pmol/kg/min) or vehicle control infusion. Myocardial VIP concentration was measured by radioimmunoassay, fibrosis was quantitated by computerised histomorphometry and changes in pro-fibrotic mediators were measured by quantitative rt-PCR.
Myocardial VIP increased significantly in VIP treated rats compared with vehicle treated controls (P < 0.01) while fibrosis in the VIP treated rats was significantly lower than in both the zero time control (P < 0.05) and the vehicle infused control (P < 0.0005). Although all six profibrotic mediators which were measured increased over the 4 week experimental period VIP infusion only affected angiotensinogen (Agt) and angiotensin receptor type 1a (AT1a) expression. In both instances VIP caused a significant decrease in messenger rna expression (Agt P < 0.01 and At1a P < 0.01) compared with vehicle infused controls.
We conclude that VIP infusion increased myocardial VIP concentration and was able to reverse existing myocardial fibrosis suggesting a possible therapeutic role for a VIP based therapy in cardiac failure.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2019.172629</identifier><identifier>PMID: 31449808</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Angiotensinogen - analysis ; Angiotensinogen - metabolism ; Animals ; Biomarkers - analysis ; Biomarkers - metabolism ; Cardiomyopathies - diagnosis ; Cardiomyopathies - drug therapy ; Cardiomyopathies - etiology ; Disease Models, Animal ; Fibrosis ; Heart failure ; Humans ; Infusions, Intravenous ; Male ; Myocardial fibrosis ; Myocardium - metabolism ; Myocardium - pathology ; Rats ; Rats, Inbred WKY ; Receptor, Angiotensin, Type 1 - analysis ; Receptor, Angiotensin, Type 1 - metabolism ; Sodium, Dietary - adverse effects ; Vasoactive intestinal peptide ; Vasoactive Intestinal Peptide - administration & dosage ; Vasoactive Intestinal Peptide - analysis ; Vasoactive Intestinal Peptide - metabolism</subject><ispartof>European journal of pharmacology, 2019-11, Vol.862, p.172629-172629, Article 172629</ispartof><rights>2019 Vectus Biosystems</rights><rights>Copyright © 2019 Vectus Biosystems. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-c75bac6fed7121274f767798dafb2ac96d78bb06991faa512232b4a965dc979a3</citedby><cites>FETCH-LOGICAL-c408t-c75bac6fed7121274f767798dafb2ac96d78bb06991faa512232b4a965dc979a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014299919305813$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31449808$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Duggan, Karen A.</creatorcontrib><creatorcontrib>Hodge, George</creatorcontrib><creatorcontrib>Chen, Juchuan</creatorcontrib><creatorcontrib>Hunter, Tegan</creatorcontrib><title>Vasoactive intestinal peptide infusion reverses existing myocardial fibrosis in the rat</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Congestive cardiac failure has become one of the major health challenges of the 21st century and new therapies are needed to address this problem. The concentration of vasoactive intestinal peptide (VIP) in the heart has been shown to decrease as fibrosis (the pathology leading to heart failure) increases and to become undetectable in end stage cardiomyopathy. We sought to determine whether replenishment of myocardial VIP might treat myocardial fibrosis and therefore represent a new therapeutic target.
Wistar Kyoto rats on a high (4.4%) salt diet were randomised to zero time control, 4 week infusion of VIP (5 pmol/kg/min) or vehicle control infusion. Myocardial VIP concentration was measured by radioimmunoassay, fibrosis was quantitated by computerised histomorphometry and changes in pro-fibrotic mediators were measured by quantitative rt-PCR.
Myocardial VIP increased significantly in VIP treated rats compared with vehicle treated controls (P < 0.01) while fibrosis in the VIP treated rats was significantly lower than in both the zero time control (P < 0.05) and the vehicle infused control (P < 0.0005). Although all six profibrotic mediators which were measured increased over the 4 week experimental period VIP infusion only affected angiotensinogen (Agt) and angiotensin receptor type 1a (AT1a) expression. In both instances VIP caused a significant decrease in messenger rna expression (Agt P < 0.01 and At1a P < 0.01) compared with vehicle infused controls.
We conclude that VIP infusion increased myocardial VIP concentration and was able to reverse existing myocardial fibrosis suggesting a possible therapeutic role for a VIP based therapy in cardiac failure.</description><subject>Angiotensinogen - analysis</subject><subject>Angiotensinogen - metabolism</subject><subject>Animals</subject><subject>Biomarkers - analysis</subject><subject>Biomarkers - metabolism</subject><subject>Cardiomyopathies - diagnosis</subject><subject>Cardiomyopathies - drug therapy</subject><subject>Cardiomyopathies - etiology</subject><subject>Disease Models, Animal</subject><subject>Fibrosis</subject><subject>Heart failure</subject><subject>Humans</subject><subject>Infusions, Intravenous</subject><subject>Male</subject><subject>Myocardial fibrosis</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Rats</subject><subject>Rats, Inbred WKY</subject><subject>Receptor, Angiotensin, Type 1 - analysis</subject><subject>Receptor, Angiotensin, Type 1 - metabolism</subject><subject>Sodium, Dietary - adverse effects</subject><subject>Vasoactive intestinal peptide</subject><subject>Vasoactive Intestinal Peptide - administration & dosage</subject><subject>Vasoactive Intestinal Peptide - analysis</subject><subject>Vasoactive Intestinal Peptide - metabolism</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLxDAQx4Mo7rr6DUR69NKapI80F0EWX7DgxccxpMnUTenLpF3cb29KV4-eBobfzPznh9AlwRHBJLupIqj6rbQRxYRHhNGM8iO0JDnjIWaEHqMlxiQJKed8gc6cqzDGKafpKVrEJEl4jvMl-niXrpNqMDsITDuAG0wr66CHfjB6apWjM10bWNiBdeAC-DYT8xk0-05Jq42nS1PYzhnn8WDYQmDlcI5OSlk7uDjUFXp7uH9dP4Wbl8fn9d0mVAnOh1CxtJAqK0H7xISypGQZYzzXsiyoVDzTLC8KnHFOSilTQmlMi0TyLNWKMy7jFbqe9_a2-xp9fNEYp6CuZQvd6ASlOfG64jzxaDKjyod1FkrRW9NIuxcEi0mpqMSsVExKxazUj10dLoxFA_pv6NehB25nAPyfOwNWOGWgVaCNBTUI3Zn_L_wAetaK-g</recordid><startdate>20191105</startdate><enddate>20191105</enddate><creator>Duggan, Karen A.</creator><creator>Hodge, George</creator><creator>Chen, Juchuan</creator><creator>Hunter, Tegan</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20191105</creationdate><title>Vasoactive intestinal peptide infusion reverses existing myocardial fibrosis in the rat</title><author>Duggan, Karen A. ; Hodge, George ; Chen, Juchuan ; Hunter, Tegan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-c75bac6fed7121274f767798dafb2ac96d78bb06991faa512232b4a965dc979a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Angiotensinogen - analysis</topic><topic>Angiotensinogen - metabolism</topic><topic>Animals</topic><topic>Biomarkers - analysis</topic><topic>Biomarkers - metabolism</topic><topic>Cardiomyopathies - diagnosis</topic><topic>Cardiomyopathies - drug therapy</topic><topic>Cardiomyopathies - etiology</topic><topic>Disease Models, Animal</topic><topic>Fibrosis</topic><topic>Heart failure</topic><topic>Humans</topic><topic>Infusions, Intravenous</topic><topic>Male</topic><topic>Myocardial fibrosis</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Rats</topic><topic>Rats, Inbred WKY</topic><topic>Receptor, Angiotensin, Type 1 - analysis</topic><topic>Receptor, Angiotensin, Type 1 - metabolism</topic><topic>Sodium, Dietary - adverse effects</topic><topic>Vasoactive intestinal peptide</topic><topic>Vasoactive Intestinal Peptide - administration & dosage</topic><topic>Vasoactive Intestinal Peptide - analysis</topic><topic>Vasoactive Intestinal Peptide - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Duggan, Karen A.</creatorcontrib><creatorcontrib>Hodge, George</creatorcontrib><creatorcontrib>Chen, Juchuan</creatorcontrib><creatorcontrib>Hunter, Tegan</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>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Duggan, Karen A.</au><au>Hodge, George</au><au>Chen, Juchuan</au><au>Hunter, Tegan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vasoactive intestinal peptide infusion reverses existing myocardial fibrosis in the rat</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2019-11-05</date><risdate>2019</risdate><volume>862</volume><spage>172629</spage><epage>172629</epage><pages>172629-172629</pages><artnum>172629</artnum><issn>0014-2999</issn><eissn>1879-0712</eissn><abstract>Congestive cardiac failure has become one of the major health challenges of the 21st century and new therapies are needed to address this problem. The concentration of vasoactive intestinal peptide (VIP) in the heart has been shown to decrease as fibrosis (the pathology leading to heart failure) increases and to become undetectable in end stage cardiomyopathy. We sought to determine whether replenishment of myocardial VIP might treat myocardial fibrosis and therefore represent a new therapeutic target.
Wistar Kyoto rats on a high (4.4%) salt diet were randomised to zero time control, 4 week infusion of VIP (5 pmol/kg/min) or vehicle control infusion. Myocardial VIP concentration was measured by radioimmunoassay, fibrosis was quantitated by computerised histomorphometry and changes in pro-fibrotic mediators were measured by quantitative rt-PCR.
Myocardial VIP increased significantly in VIP treated rats compared with vehicle treated controls (P < 0.01) while fibrosis in the VIP treated rats was significantly lower than in both the zero time control (P < 0.05) and the vehicle infused control (P < 0.0005). Although all six profibrotic mediators which were measured increased over the 4 week experimental period VIP infusion only affected angiotensinogen (Agt) and angiotensin receptor type 1a (AT1a) expression. In both instances VIP caused a significant decrease in messenger rna expression (Agt P < 0.01 and At1a P < 0.01) compared with vehicle infused controls.
We conclude that VIP infusion increased myocardial VIP concentration and was able to reverse existing myocardial fibrosis suggesting a possible therapeutic role for a VIP based therapy in cardiac failure.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31449808</pmid><doi>10.1016/j.ejphar.2019.172629</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Angiotensinogen - analysis Angiotensinogen - metabolism Animals Biomarkers - analysis Biomarkers - metabolism Cardiomyopathies - diagnosis Cardiomyopathies - drug therapy Cardiomyopathies - etiology Disease Models, Animal Fibrosis Heart failure Humans Infusions, Intravenous Male Myocardial fibrosis Myocardium - metabolism Myocardium - pathology Rats Rats, Inbred WKY Receptor, Angiotensin, Type 1 - analysis Receptor, Angiotensin, Type 1 - metabolism Sodium, Dietary - adverse effects Vasoactive intestinal peptide Vasoactive Intestinal Peptide - administration & dosage Vasoactive Intestinal Peptide - analysis Vasoactive Intestinal Peptide - metabolism |
| title | Vasoactive intestinal peptide infusion reverses existing myocardial fibrosis in the rat |
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