{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:26:02Z","timestamp":1772101562834,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Medicine, Universiti Kebangsaan Malaysia","award":["FF-2023-299"],"award-info":[{"award-number":["FF-2023-299"]}]},{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education, Malaysia","doi-asserted-by":"publisher","award":["FRGS\/1\/2019\/SKK08\/UKM\/03\/2"],"award-info":[{"award-number":["FRGS\/1\/2019\/SKK08\/UKM\/03\/2"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Offspring of hypertensive disorders of pregnancies (HDP) exhibit early-life endothelial dysfunction and have an elevated susceptibility to hypertension during adulthood which is potentially mediated by microRNA (miRNA), a key regulator of gene expression. RNA sequencing showed that miR-196a-5p was significantly upregulated in HUVEC exposed to HDP and may regulate angiogenesis in endothelial cells. Therefore, this study aims to elucidate the role of miR-196a-5p in regulating angiogenesis in HUVEC exposed to HDP. miR-196a-5p expression was validated by stem-loop RT-qPCR. Predicted target genes were identified using four algorithms, miRWalk, miRDB, TargetScan, and DIANA-microT-CDS, focusing on angiogenesis-related genes. Protein expression was confirmed through ELISA. Stem-loop RT-qPCR showed that miR-196a-5p expression was significantly upregulated in HDP HUVEC. Bioinformatic analysis revealed that the PDGFRA gene, a key regulator for angiogenesis, was significantly enriched. Overexpression of miR-196a-5p significantly downregulated PDGFRA, VEGF, and bFGF in HDP HUVEC, whereas its suppression upregulated these genes significantly. The ELISA result confirmed the corresponding changes at the protein level. However, PDGFRA protein levels increased with miR-196a-5p overexpression and decreased with its inhibition. Collectively, the results indicate that miR-196a-5p may have a regulatory effect on PDGFRA, VEGF, and bFGF that is associated with angiogenesis, and the modifications could be beneficial in future epigenetic targeted therapy.<\/jats:p>","DOI":"10.3390\/ijms27042047","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T08:58:21Z","timestamp":1771837101000},"page":"2047","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulatory Role of miR-196a-5p in Angiogenesis-Related Markers in Endothelial Cells Exposed to Hypertensive Pregnancies"],"prefix":"10.3390","volume":"27","author":[{"given":"Aslah Nabilah Abdull","family":"Sukor","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Universiti Teknologi Mara, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh 47000, Selangor, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurul Iffah","family":"Mohd Isa","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nur Syakirah","family":"Othman","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8268-3316","authenticated-orcid":false,"given":"Azizah","family":"Ugusman","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia"},{"name":"Cardiovascular and Pulmonary (CardioResp) Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2735-3274","authenticated-orcid":false,"given":"Mohd Faizal","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1442-5555","authenticated-orcid":false,"given":"Nur Fariha Mohd","family":"Manzor","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai 71800, Negeri Sembilan, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahidee Zainal","family":"Abidin","sequence":"additional","affiliation":[{"name":"Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus 21030, Terengganu, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1329-0444","authenticated-orcid":false,"given":"Amilia","family":"Aminuddin","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia"},{"name":"Cardiovascular and Pulmonary (CardioResp) Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adila A.","family":"Hamid","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia"},{"name":"Cardiovascular and Pulmonary (CardioResp) Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13690-024-01349-7","article-title":"Prevalence of hypertension in pregnancy and its associated sociodemographic factors among mothers aged 15\u201349 years old in Malaysia","volume":"82","author":"Ratnam","year":"2024","journal-title":"Arch. 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