{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:32:03Z","timestamp":1783629123983,"version":"3.55.0"},"reference-count":138,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["130992"],"award-info":[{"award-number":["130992"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This review explored the role of vascular endothelial growth factor receptor-2 (VEGFR-2) in the synergy of preeclampsia (PE), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Downregulation of VEGFR-2 in PE promotes endothelial dysfunction and prevents endothelial cell (EC) migration, proliferation, and differentiation. The HIV-1 accessory protein, tat (trans-activator of transcription), prevents VEGFR-2 signaling via the vascular endothelial growth factor A (VEGF-A) ligand. Combined antiretroviral therapy (cART) may cause immune reconstitution, impaired decidualization, and endothelial injury, thus may be a risk factor for PE development. The VEGF\/VEGFR-2 interaction may be associated with SARS-CoV-2-related pulmonary oedema. Endothelial dysfunction and heightened inflammation are both associated with PE, HIV, and SARS-CoV-2 infection; therefore, it is plausible that both characteristics may be exacerbated in the synergy of these events. In addition, this review explored microRNAs (miR) regulating VEGFR-2. An overexpression of miR-126 is evident in PE, HIV, and SARS-CoV-2 infection; thus, modulating the expression of miR-126 may be a therapeutic strategy. However, the involvement of microRNAs in PE, HIV, and SARS-CoV-2 infection needs further investigating. Since these conditions have been evaluated independently, this review attempts to predict their clinical manifestations in their synergy, as well as independently; thereby providing a platform for early diagnosis and therapeutic potential in PE, HIV, and SARS-CoV-2 infection.<\/jats:p>","DOI":"10.3390\/ijms232213752","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T02:34:52Z","timestamp":1667961292000},"page":"13752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Vascular Endothelial Growth Factor Receptor 2: Molecular Mechanism and Therapeutic Potential in Preeclampsia Comorbidity with Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7808-6161","authenticated-orcid":false,"given":"Tashlen","family":"Abel","sequence":"first","affiliation":[{"name":"Women\u2019s Health and HIV Research Group, Department of Obstetrics & Gynaecology, School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagidesa","family":"Moodley","sequence":"additional","affiliation":[{"name":"Women\u2019s Health and HIV Research Group, Department of Obstetrics & Gynaecology, School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olive P.","family":"Khaliq","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Faculty of Health Sciences, The University of the Free State, Bloemfontein 9300, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thajasvarie","family":"Naicker","sequence":"additional","affiliation":[{"name":"Optics and Imaging Centre, Doris Duke Medical Research Institution, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, September 10). 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