{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:12:24Z","timestamp":1787807544743,"version":"build-2784847793"},"reference-count":35,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p>Preeclampsia (PE) is one of the leading causes of fetal and maternal morbidity, affecting 5\u201310% of all pregnancies, and lacks an effective treatment. The exact etiology of the disorder is unclear, but placental ischemia has been shown to be a central causative agent. In response to placental ischemia, the antiangiogenic protein fms-like tyrosine kinase-1 (sFlt-1), a VEGF antagonist, and reactive oxygen species are secreted, leading to the maternal syndrome. One promising therapeutic approach to treat PE is through manipulation of the heme oxygenase-1 (HO-1) protein. It has been previously reported that HO-1 and carbon monoxide downregulate sFlt-1 production in vitro, and we have recently shown that HO-1 induction significantly attenuates placental ischemia-induced hypertension, partially through normalization of the sFlt-1-to-VEGF ratio in the placenta. The purpose of this study was to determine whether HO-1 induction would have beneficial effects independently of sFlt-1 suppression. To that end, pregnant rats were continuously infused with recombinant sFlt-1 from gestational days 14\u201319, and circulating sFlt-1 increased approximately twofold, similar to rats with experimentally induced placental ischemia. In response, mean arterial pressure increased 17 mmHg, which was completely normalized by HO-1 induction. Unbound circulating VEGF was decreased \u223c17% in response to sFlt-1 infusion but was increased \u223c50% in response to HO-1 induction. Finally, endothelial function was improved as measured by reductions in vascular expression of preproendothelin mRNA. In conclusion, manipulation of HO-1 presents an intriguing therapeutic approach to the treatment of PE.<\/jats:p>","DOI":"10.1152\/ajpregu.00325.2011","type":"journal-article","created":{"date-parts":[[2011,8,25]],"date-time":"2011-08-25T03:52:42Z","timestamp":1314244362000},"page":"R1495-R1500","source":"Crossref","is-referenced-by-count":52,"title":["Induction of heme oxygenase-1 attenuates sFlt-1-induced hypertension in pregnant rats"],"prefix":"10.1152","volume":"301","author":[{"given":"Eric M.","family":"George","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marietta","family":"Arany","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of 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