{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:32:09Z","timestamp":1773289929133,"version":"3.50.1"},"reference-count":47,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:p>Oxidative stress is implicated in menopause-associated hypertension and cardiovascular disease. The role of antioxidants in this process is unclear. We questioned whether the downregulation of thioredoxin (TRX) is associated with oxidative stress and the development of hypertension and target-organ damage (cardiac hypertrophy) in a menopause model. TRX is an endogenous antioxidant that also interacts with signaling molecules, such as apoptosis signal-regulated kinase 1 (ASK-1), independently of its antioxidant function. Aged female wild-type (WT) and follitropin receptor knockout (FORKO) mice (20\u201324 wk), with hormonal imbalances, were studied. Mice were infused with ANG II (400 ng\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>; 14 days). Systolic blood pressure was increased by ANG II in WT (166 \u00b1 8 vs. 121 \u00b1 5 mmHg) and FORKO (176 \u00b1 7 vs. 115 \u00b1 5 mmHg; P &lt; 0.0001; n = 9\/group) mice. In ANG II-infused FORKO mice, cardiac mass was increased by 42% ( P &lt; 0.001). This was associated with increased collagen content and augmented ERK1\/2 phosphorylation (2-fold). Cardiac TRX expression and activity were decreased by ANG II in FORKO but not in WT ( P &lt; 0.01) mice. ASK-1 expression, cleaved caspase III content, and Bax\/Bcl-2 content were increased in ANG II-infused FORKO ( P &lt; 0.05). ANG II had no effect on cardiac NAD(P)H oxidase activity or on O<jats:sub>2<\/jats:sub><jats:sup>\u2022\u2212<\/jats:sup>levels in WT or FORKO. Cardiac ANG II type 1 receptor expression was similar in FORKO and WT. These findings indicate that in female FORKO, ANG II-induced cardiac hypertrophy and fibrosis are associated with the TRX downregulation and upregulation of ASK-1\/caspase signaling. Our data suggest that in a model of menopause, protective actions of TRX may be blunted, which could contribute to cardiac remodeling independently of oxidative stress and hypertension.<\/jats:p>","DOI":"10.1152\/ajpheart.00163.2008","type":"journal-article","created":{"date-parts":[[2008,8,2]],"date-time":"2008-08-02T01:10:09Z","timestamp":1217639409000},"page":"H1481-H1488","source":"Crossref","is-referenced-by-count":21,"title":["Cardiac hypertrophy is associated with altered thioredoxin and ASK-1 signaling in a mouse model of menopause"],"prefix":"10.1152","volume":"295","author":[{"given":"Talin","family":"Ebrahimian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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