{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:15:37Z","timestamp":1754144137202,"version":"3.41.2"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:00:00Z","timestamp":1743292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although uterine matrix metalloproteinases (MMPs) are known to play a role in the development of pre-eclampsia (PE), it remains unclear whether increased levels of serum MMPs are the pathogenesis underlying pregnancy-induced hypertension (PIH). This study investigated whether serum MMP2 and MMP9 contributes to PIH pathogenesis using a specific inhibitor, SB-3CT. Twenty-five nine-week-old pregnant rats were randomly divided into five groups: SHAM (normal pregnancy), RUPP (PE model), and three SB-3CT intervention groups (25, 50, 75 mg\/kg\/d). After 7 days of intraperitoneal injections, carotid artery blood pressure was measured. Serum MMP2, MMP9, tissue inhibitor of metalloproteinase-1 (TIMP1), endothelin-1 (ET-1), angiotensin II (Ang II), and endothelial nitric oxide synthase (eNOS) levels were tested by ELISA. Vascular wall changes in cross-sections of the aorta abdominalis were observed using H&amp;E-staining and the activities of MMP2 and MMP9 in the aorta abdominalis were tested using gelatin zymography. There were significant increases in blood pressure, serum MMP2 and MMP9 levels, and activities of MMP2 and MMP9 in the aorta abdominalis, along with notable vascular remodeling in the RUPP group. After the SB-3CT intervention, increased blood pressure was relieved and vascular remodeling improved, while MMP2 and MMP9 levels and activities were reduced. In summary, specific inhibition of MMP2 and MMP9 can decrease blood pressure in a PIH model. This indicates that increased MMP2 and MMP9 in maternal serum might contribute to the pathogenesis of PIH.<\/jats:p>","DOI":"10.1093\/biolre\/ioaf075","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T16:30:37Z","timestamp":1743438637000},"page":"209-219","source":"Crossref","is-referenced-by-count":0,"title":["The MMP2 and MMP9-specific inhibitor SB-3CT significantly decreases blood pressure in pre-eclampsia model rats"],"prefix":"10.1093","volume":"113","author":[{"given":"Bowei","family":"Li","sequence":"first","affiliation":[{"name":"The Second School of Clinical Medicine, Southern Medical University , 1023-1063, Shatai Nan Road, Baiyun District, Guangzhou, Guangdong ,","place":["China"]},{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences , 106 Zhongshan er Road, Yuexiu District, Guangzhou, Guangdong ,","place":["China"]},{"name":"Department of Internal Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University (School of Clinical Medicine) , No. 19 Nonglin Xia Road, Yuexiu District, Guangzhou, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianfang","family":"Luo","sequence":"additional","affiliation":[{"name":"The Second School of Clinical Medicine, Southern Medical University , 1023-1063, Shatai Nan Road, Baiyun District, Guangzhou, Guangdong ,","place":["China"]},{"name":"Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences , 106 Zhongshan er Road, Yuexiu District, Guangzhou, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanxing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Internal Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University (School of Clinical Medicine) , No. 19 Nonglin Xia Road, Yuexiu District, Guangzhou, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,3,30]]},"reference":[{"key":"2025071504315287600_ref1","doi-asserted-by":"crossref","first-page":"102481","DOI":"10.1016\/j.bpobgyn.2024.102481","article-title":"Prevention of preeclampsia","volume":"93","author":"Brownfoot","year":"2024","journal-title":"Best Pract Res Clin ObstetGynaecol"},{"key":"2025071504315287600_ref2","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1007\/s00404-024-07393-6","article-title":"Advances in pathogenesis of preeclampsia","volume":"309","author":"Yang","year":"2024","journal-title":"Arch Gynecol Obstet"},{"key":"2025071504315287600_ref3","doi-asserted-by":"crossref","first-page":"9739","DOI":"10.3390\/ijms21249739","article-title":"The roles of matrix Metalloproteinases and their inhibitors in human diseases","volume":"21","author":"Cabral-Pacheco","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2025071504315287600_ref4","doi-asserted-by":"crossref","first-page":"480","DOI":"10.3390\/diagnostics11030480","article-title":"Role of gelatinases MMP2 and MMP9 in healthy and complicated pregnancy and their future potential as preeclampsia biomarkers","volume":"11","author":"Nikolov","year":"2021","journal-title":"Diagnostics (Basel)"},{"key":"2025071504315287600_ref5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/6432426","article-title":"Altered maternal serum matrix Metalloproteinases MMP2, MMP-3, MMP9, and MMP-13 in severe early- and late-onset preeclampsia","volume":"2017","author":"Laskowska","year":"2017","journal-title":"Biomed Res Int"},{"key":"2025071504315287600_ref6","first-page":"17442","article-title":"Research on correlation between MMP9 and early-onset preeclampsia","volume":"9","author":"Meng","year":"2016","journal-title":"Int J Clin ExpMed"},{"key":"2025071504315287600_ref7","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1111\/j.1471-0528.2004.00223.x","article-title":"The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre-eclampsia","volume":"111","author":"Merchant","year":"2004","journal-title":"BJOG"},{"key":"2025071504315287600_ref8","doi-asserted-by":"crossref","first-page":"1659771","DOI":"10.1155\/2022\/1659771","article-title":"Injection of matrix Metalloproteinase-9 leads to ventricular Remodeling","volume":"2022","author":"Zhu","year":"2022","journal-title":"Dis Markers"},{"key":"2025071504315287600_ref9","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00117.2012","article-title":"A model of preeclampsia in rats: the reduced uterine perfusion pressure (RUPP) model","volume":"303","author":"Li","year":"2012","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2025071504315287600_ref10","doi-asserted-by":"crossref","first-page":"R1495","DOI":"10.1152\/ajpregu.00325.2011","article-title":"Induction of heme oxygenase-1 attenuates sFlt-1-induced hypertension in pregnant rats","volume":"301","author":"George","year":"2011","journal-title":"Am J PhysiolRegulIntegr Comp Physiol"},{"key":"2025071504315287600_ref11","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1161\/HYPERTENSIONAHA.108.120576","article-title":"Autoantibodies to the angiotensin type I receptor in response to placental ischemia and tumor necrosis factor alpha in pregnant rats","volume":"52","author":"LaMarca","year":"2008","journal-title":"Hypertension"},{"key":"2025071504315287600_ref12","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1161\/HYPERTENSIONAHA.107.096594","article-title":"Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble fms-like tyrosine kinase-1 expression","volume":"50","author":"Gilbert","year":"2007","journal-title":"Hypertension"},{"key":"2025071504315287600_ref13","first-page":"325","article-title":"Matrix metalloproteinases as drug targets in preeclampsia","volume":"14","author":"Palei","year":"2013","journal-title":"Curr Drug Targets"},{"key":"2025071504315287600_ref14","doi-asserted-by":"crossref","first-page":"12818","DOI":"10.3390\/ijms241612818","article-title":"Sodium nitrite attenuates reduced activity of vascular matrix Metalloproteinase-2 and vascular hyper-reactivity and increased systolic blood pressure induced by the placental ischemia model of preeclampsia in anesthetized rats","volume":"24","author":"Martins","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2025071504315287600_ref15","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/bs.pmbts.2017.04.001","article-title":"Matrix Metalloproteinases in normal pregnancy and preeclampsia","volume":"148","author":"Chen","year":"2017","journal-title":"Prog Mol Biol Transl Sci"},{"key":"2025071504315287600_ref16","doi-asserted-by":"crossref","first-page":"e0167102","DOI":"10.1371\/journal.pone.0167102","article-title":"Inhibition of matrix metalloproteinase 9 enhances rod survival in the S334ter-line3 retinitis Pigmentosa model","volume":"11","author":"Shin","year":"2016","journal-title":"PloS One"},{"key":"2025071504315287600_ref17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13073-020-00780-z","article-title":"Small-molecule MMP2\/MMP9 inhibitor SB-3CT modulates tumor immune surveillance by regulating PD-L1","volume":"12","author":"Ye","year":"2020","journal-title":"Genome Med"},{"key":"2025071504315287600_ref18","doi-asserted-by":"crossref","first-page":"20140070","DOI":"10.1098\/rstb.2014.0070","article-title":"The role of invasive trophoblast in implantation and placentation of primates","volume":"370","author":"Carter","year":"2015","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"2025071504315287600_ref19","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/biof.1325","article-title":"miR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9","volume":"43","author":"Su","year":"2017","journal-title":"Biofactors"},{"key":"2025071504315287600_ref20","first-page":"370","article-title":"Altered matrix metalloproteinase-2 and -9 expression\/activity links placental ischemia and anti-angiogenic sFlt-1 to uteroplacental and vascular remodeling and collagen deposition in hypertensive pregnancy","volume":"89","author":"Li","year":"2014","journal-title":"BiochemPharmacol"},{"key":"2025071504315287600_ref21","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ejphar.2018.10.017","article-title":"Hypertension, augmented activity of matrix metalloproteinases-2 and -9 and angiogenic imbalance in hypertensive pregnancy are attenuated by doxycycline","volume":"840","author":"Nascimento","year":"2018","journal-title":"Eur J Pharmacol"},{"key":"2025071504315287600_ref22","doi-asserted-by":"crossref","first-page":"e12508","DOI":"10.1111\/micc.12508","article-title":"Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia","volume":"26","author":"Yu","year":"2018","journal-title":"Microcirculation"},{"key":"2025071504315287600_ref23","first-page":"115963","article-title":"Regulation of vascular angiotensin II type 1 and type 2 receptor and angiotensin-(1-7)\/MasR signaling in normal and hypertensive pregnancy","volume":"220","author":"Clark","year":"2024","journal-title":"BiochemPharmacol"},{"key":"2025071504315287600_ref24","doi-asserted-by":"crossref","first-page":"H393","DOI":"10.1152\/ajpheart.00247.2002","article-title":"Enhanced [Ca2+]i in renal arterial smooth muscle cells of pregnant rats with reduced uterine perfusion pressure","volume":"284","author":"Murphy","year":"2003","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2025071504315287600_ref25","first-page":"1848","article-title":"Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1\/FOXO3a\/MMP signaling pathway","volume":"45","author":"Lu","year":"2024","journal-title":"ActaPharmacol Sin"},{"key":"2025071504315287600_ref26","doi-asserted-by":"crossref","first-page":"S945","DOI":"10.1016\/j.ajog.2021.11.1367","article-title":"Pregnancy-specific expression of protease-activated receptor 1: a therapeutic target for prevention and treatment of preeclampsia?","volume":"226","author":"Walsh","year":"2022","journal-title":"Am J Obstet Gynecol"},{"key":"2025071504315287600_ref27","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1177\/1933719115607998","article-title":"Matrix metalloproteinase 1 causes vasoconstriction and enhances vessel reactivity to angiotensin II via protease-activated receptor 1","volume":"23","author":"Nugent","year":"2016","journal-title":"Reprod Sci"},{"key":"2025071504315287600_ref28","doi-asserted-by":"crossref","first-page":"e0171427","DOI":"10.1371\/journal.pone.0171427","article-title":"Metalloproteinase-9 contributes to endothelial dysfunction in atherosclerosis via protease activated receptor-1","volume":"12","author":"Florence","year":"2017","journal-title":"PloS One"},{"key":"2025071504315287600_ref29","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1161\/01.RES.85.10.906","article-title":"Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor","volume":"85","author":"Fernandez-Patron","year":"1999","journal-title":"Circ Res"},{"key":"2025071504315287600_ref30","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1096\/fj.01-0178com","article-title":"Matrix metalloproteinases regulate neutrophil-endothelial cell adhesion through generation of endothelin-1[1-32]","volume":"15","author":"Fernandez-Patron","year":"2001","journal-title":"FASEB J"},{"key":"2025071504315287600_ref31","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3390\/biom11040585","article-title":"Matrix Metalloproteinases and arterial hypertension: role of oxidative stress and nitric oxide in vascular functional and structural alterations","volume":"11","author":"Prado","year":"2021","journal-title":"Biomolecules"},{"key":"2025071504315287600_ref32","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.4049\/jimmunol.170.6.3369","article-title":"IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis","volume":"170","author":"Li","year":"2003","journal-title":"J Immunol"},{"key":"2025071504315287600_ref33","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1161\/01.ATV.0000151373.33830.41","article-title":"Matrix metalloproteinase-9 (MMP9), MMP2, and serum elastase activity are associated with systolic hypertension and arterial stiffness","volume":"25","author":"Yasmin","year":"2005","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2025071504315287600_ref34","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/jcla.20295","article-title":"Evaluation of metalloproteinases 2 and 9 and their inhibitors in physiologic and pre-eclamptic pregnancy","volume":"23","author":"Montagnana","year":"2009","journal-title":"J Clin Lab Anal"},{"key":"2025071504315287600_ref35","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3389\/fphys.2014.00372","article-title":"Endothelial dysfunction and preeclampsia: role of oxidative stress","volume":"5","author":"S\u00e1nchez-Aranguren","year":"2014","journal-title":"Front Physiol"},{"key":"2025071504315287600_ref36","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/eurheartj\/ehr304","article-title":"Nitric oxide synthases: regulation and function","volume":"33","author":"F\u00f6rstermann","year":"2012","journal-title":"Eur Heart J"},{"key":"2025071504315287600_ref37","first-page":"257","article-title":"Nitric oxide production increases during normal pregnancy and decreases in preeclampsia","volume":"32","author":"Choi","year":"2002","journal-title":"Ann Clin Lab Sci"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioaf075\/62811519\/ioaf075.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/113\/1\/209\/62811519\/ioaf075.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/113\/1\/209\/62811519\/ioaf075.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T08:32:13Z","timestamp":1752568333000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/113\/1\/209\/8100522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,30]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,3,30]]},"published-print":{"date-parts":[[2025,7,13]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioaf075","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"type":"print","value":"0006-3363"},{"type":"electronic","value":"1529-7268"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,3,30]]}}}