{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T05:20:55Z","timestamp":1762752055530,"version":"build-2065373602"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alpha-calcitonin gene-related peptide (\u03b1-CGRP) is a cardioprotective neuropeptide. However, due to low bioavailability, its use as a therapeutic agent is limited. The aim of the present study was to develop a stable and bioactive \u03b1-CGRP analog and to determine its cardioprotective effects in a mouse model of heart failure (HF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We chemically synthesized a peptide-peptoid hybrid: human \u03b1-CGRP containing two monomers of N-methoxy-ethyl glycine peptoid at the N-terminus (NMEG-CGRP). The toxicity, bioactivity, and stability of NMEG-CGRP were determined by MTT-cell viability assay, mouse blood pressure measurement, and\n                      <jats:italic>in-vitro<\/jats:italic>\n                      digestion with Insulin-degrading enzyme (IDE) followed by LC-MS, respectively. Male C57BL6 mice were underwent transverse aortic constriction (TAC) and were divided into: Sham, Sham+NMEG-CGRP, TAC, and TAC+NMEG-CGRP. Two-day post-TAC, NMEG-CGRP (3.6\u00a0mg\/kg\/mouse) was administered subcutaneously on alternate days, for a total of 28\u00a0days. Cardiac function was measured weekly using echocardiography. At the endpoint, mice were euthanized, and hearts were collected for analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results demonstrated that NMEG-CGRP was non-toxic to rat H9C2 cells, more stable to IDE digestion, and bioactive. TAC-induced pressure-overload decreased ejection fraction and increased cardiac hypertrophy and dilation, fibrosis, apoptosis, oxidative stress, and macrophage infiltration in the left ventricles. NMEG-CGRP administration significantly attenuated these TAC-induced adverse cardiac effects in the HF mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, our results demonstrated that NMEG-CGRP is a non-toxic, stable, and bioactive CGRP-analog, and protects against pressure-induced HF in mice. Thus, NMEG-CGRP is a promising novel CGRP-analog that may be used in the treatment of HF and potentially other cardiac diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1692472","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T05:17:53Z","timestamp":1762751873000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel bioactive peptide-peptoid hybrid of alpha-calcitonin gene-related peptide protects against pressure-overload induced heart failure"],"prefix":"10.3389","volume":"16","author":[{"given":"Ambrish","family":"Kumar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Deloach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lernix","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald J.","family":"DiPette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay D.","family":"Potts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1161\/HYPERTENSIONAHA.120.14851","article-title":"Calcitonin gene-related peptide protects against cardiovascular dysfunction independently of nitric oxide in vivo","volume":"77","author":"Argunhan","year":"2021","journal-title":"Hypertension"},{"key":"B2","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1161\/CIRCULATIONAHA.117.028388","article-title":"A novel alpha-calcitonin gene-related peptide analogue protects against end-organ damage in experimental hypertension, cardiac hypertrophy, and heart failure","volume":"136","author":"Aubdool","year":"2017","journal-title":"Circulation"},{"key":"B3","doi-asserted-by":"publisher","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. 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