{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:15:11Z","timestamp":1790792111909,"version":"4.1.0"},"reference-count":43,"publisher":"Scientific Scholar","content-domain":{"domain":["cytojournal.com"],"crossmark-restriction":true},"short-container-title":["Cytojournal"],"abstract":"<jats:sec id=\"st1\">\n<jats:title>Objective:<\/jats:title>\n<jats:p>Pregnancy-induced hypertension (PIH) is a common complication during pregnancy and is closely associated with vascular endothelial cell damage and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis. This study aimed to investigate whether mitophagy alleviates vascular endothelial cell damage in PIH by inhibiting NLRP3-mediated pyroptosis. The regulatory mechanisms of pyroptosis-related pathways were systematically investigated by establishing a cellular model of PIH and incorporating mitophagy intervention.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"st2\">\n<jats:title>Material and Methods:<\/jats:title>\n<jats:p>An N\u03c9-nitro-L-arginine methyl ester (L-NAME)-induced gestational hypertension model was established, and the cell samples were grouped as follows: Control group (Control), L-NAME-induced gestational hypertension group (L-NAME), mitochondrial autophagy inhibition group (L-NAME+ 3-methyladenine [3-MA]), and mitochondrial autophagy activation group (L-NAME+ rapamycin [Rapa]). Cell viability was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase (LDH) levels were measured to evaluate cell damage, and reactive oxygen species (ROS) kits were used to quantify ROS accumulation. Cell death was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling staining to detect apoptotic cells. Immunofluorescence, Western blot analysis, and quantitative real-time polymerase chain reaction were performed to assess the expression levels of proteins and genes associated with mitophagy (e.g., microtubule-associated protein 1 light chain 3 and sequestosome 1) and those linked to pyroptosis (e.g., NLRP3, gasdermin D (GSDMD), cysteinyl aspartate-specific proteinase 1 (caspase-1), interleukin (IL)-1\u03b2, and IL-18). The role of NLRP3 in pyroptosis regulation through mitochondrial autophagy was further examined using NLRP3 small interfering RNA (siNLRP3) transfection experiments.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"st3\">\n<jats:title>Results:<\/jats:title>\n<jats:p>L-NAME treatment substantially decreased vascular endothelial cell viability, elevated LDH release and ROS levels, and upregulated pyroptosis-related proteins (NLRP3, GSDMD, and caspase-1) and inflammatory factors (IL-1\u03b2 and IL-18). The inhibition of mitochondrial autophagy with 3-MA further enhanced pyroptosis and aggravated cell damage, and its activation with Rapa reduced pyroptosis, improved cell survival, and decreased LDH release and ROS levels. NLRP3 silencing (siNLRP3) significantly inhibited pyroptosis and alleviated the cell damage caused by 3-MA. Meanwhile, Rapa enhanced the protective effect of NLRP3 silencing.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"st4\">\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>This study demonstrates that mitophagy can effectively alleviate the vascular endothelial cell damage associated with PIH by inhibiting NLRP3-mediated pyroptosis. The findings provide new theoretical support for the treatment of PIH and suggest potential intervention targets.<\/jats:p>\n<\/jats:sec>","DOI":"10.25259\/cytojournal_52_2025","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:17:20Z","timestamp":1749806240000},"page":"60","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mitochondrial autophagy inhibits nucleotide-binding oligomerization domain-like receptor protein 3-mediated pyroptosis and alleviates endothelial cell injury in pregnancy-induced hypertension"],"prefix":"10.25259","volume":"22","author":[{"given":"Mengsi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Wenzhou Central Hospital, Wenzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, The Second 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