{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:01:23Z","timestamp":1776211283698,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["No. 2020YFC2003600"],"award-info":[{"award-number":["No. 2020YFC2003600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obstructive sleep apnea (OSA) is marked by chronic intermittent hypoxia (CIH) and iassociated with multiple cardiovascular complications. Isoproterenol (ISO) is commonly used to induce cardiac hypertrophy. However, the impact of CIH on ISO-induced cardiac hypertrophy and remodeling remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cardiac hypertrophy was induced in mice using ISO, with or without CIH. Echocardiography was performed to assess cardiac functions, while histological analyses were employed to evaluate the physiological modifications in the heart. Western blotting and real-time quantitative PCR were used to evaluate protein and mRNA gene expression levels, respectively. Additionally, immunofluorescence was employed to observe the morphological changes in H9C2 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CIH exacerbated ISO-induced cardiac dysfunction and cardiac pathological alterations in mice. The expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was elevated in both mice and H9C2 cells in the CIH\u2009+\u2009ISO group. Furthermore, CIH exacerbated ISO-induced cell apoptosis. We additionally observed that the PI3K\/AKT\/mTOR pathway is further activated by the co-induction of CIH and ISO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CIH exhibits a negative effect on ISO-treated mice and cells, leading to an exacerbation of cardiac dysfunction and remodeling. In addition, CIH aggravates ISO-treated cardiomyocyte apoptosis in H9C2 cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2025.1700967","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T06:40:24Z","timestamp":1767681624000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Chronic intermittent hypoxia exacerbates isoproterenol-induced cardiac hypertrophy and 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