{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:05:20Z","timestamp":1790705120088,"version":"4.1.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2017,7,25]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              Research into the therapeutic potential of \u03b1-calcitonin gene\u2013related peptide (\u03b1-CGRP) has been limited because of its peptide nature and short half-life. Here, we evaluate whether a novel potent and long-lasting (\n              <jats:italic>t<\/jats:italic>\n              <jats:sub>\u00bd<\/jats:sub>\n              \u22657 hours) acylated \u03b1-CGRP analogue (\u03b1Analogue) could alleviate and reverse cardiovascular disease in 2 distinct murine models of hypertension and heart failure in vivo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>The ability of the \u03b1Analogue to act selectively via the CGRP pathway was shown in skin by using a CGRP receptor antagonist. The effect of the \u03b1Analogue on angiotensin II\u2013induced hypertension was investigated over 14 days. Blood pressure was measured by radiotelemetry. The ability of the \u03b1Analogue to modulate heart failure was studied in an abdominal aortic constriction model of murine cardiac hypertrophy and heart failure over 5 weeks. Extensive ex vivo analysis was performed via RNA analysis, Western blot, and histology.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              The angiotensin II\u2013induced hypertension was attenuated by cotreatment with the \u03b1Analogue (50 nmol\u00b7kg\n              <jats:sup>\u20131<\/jats:sup>\n              \u00b7d\n              <jats:sup>\u20131<\/jats:sup>\n              , SC, at a dose selected for lack of long-term hypotensive effects at baseline). The \u03b1Analogue protected against vascular, renal, and cardiac dysfunction, characterized by reduced hypertrophy and biomarkers of fibrosis, remodeling, inflammation, and oxidative stress. In a separate study, the \u03b1Analogue reversed angiotensin II\u2013induced hypertension and associated vascular and cardiac damage. The \u03b1Analogue was effective over 5 weeks in a murine model of cardiac hypertrophy and heart failure. It preserved heart function, assessed by echocardiography, while protecting against adverse cardiac remodeling and apoptosis. Moreover, treatment with the \u03b1Analogue was well tolerated with neither signs of desensitization nor behavioral changes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>These findings, in 2 distinct models, provide the first evidence for the therapeutic potential of a stabilized \u03b1Analogue, by mediating (1) antihypertensive effects, (2) attenuating cardiac remodeling, and (3) increasing angiogenesis and cell survival to protect against and limit damage associated with the progression of cardiovascular diseases. This indicates the therapeutic potential of the CGRP pathway and the possibility that this injectable CGRP analogue may be effective in cardiac disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.117.028388","type":"journal-article","created":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T01:00:25Z","timestamp":1493254825000},"page":"367-383","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":102,"title":["A Novel \u03b1-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure"],"prefix":"10.1161","volume":"136","author":[{"given":"Aisah A.","family":"Aubdool","sequence":"first","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratish","family":"Thakore","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulye","family":"Argunhan","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah-Jane","family":"Smillie","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Schnelle","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salil","family":"Srivastava","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija M.","family":"Alawi","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Wilde","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Mitchell","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Farrell-Dillon","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Richards","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Maltese","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); Institute of Pharmaceutical Sciences, King\u2019s College London, United Kingdom (P.T., M.N.); Cardiovascular Division, BHF Centre of Research Excellence, James Black Centre, King\u2019s College London, United Kingdom (M.S., D.A.R., A.M.S.); Department of Cardiology and Pneumology, Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Siow","sequence":"additional","affiliation":[{"name":"From Cardiovascular Division, BHF Centre of Research Excellence and Centre of Integrative Biomedicine, King\u2019s College London, United Kingdom (A.A.A., F.A., S.-J.S., S.S., K.M.A., E.W., J.M., K.F.-D., G.M., R.C.S., S.D.B.); 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