{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:53:23Z","timestamp":1774432403287,"version":"3.50.1"},"reference-count":33,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:p>Rupture of abdominal aortic aneurysm (AAA) is unpredictable and lethal. A clinically valid biomarker to monitor the disease has not been available. Based on our recent discoveries that uncoupled endothelial nitric oxide synthase (eNOS)\/tetrahydrobiopterin deficiency plays a causal role in various models of AAA, the present study examined the relationship between circulating and tissue levels of tetrahydrobiopterin (H<jats:sub>4<\/jats:sub>B) in angiotensin II-infused hyperphenylalaninemia (hph-1) and apoE null mice. For apoE null mice, tissue and plasma H<jats:sub>4<\/jats:sub>B levels decreased time dependently, to 2.69 \u00b1 0.15 and 1.99 \u00b1 0.06 pmol\/mg, respectively (from 4.86 \u00b1 0.32 and 3.31 \u00b1 0.13 pmol\/mg at baseline) by week 3, when aneurysms developed. For hph-1 mice, tissue and plasma H<jats:sub>4<\/jats:sub>B levels decreased significantly to 1.02 \u00b1 0.10 and 0.98 \u00b1 0.09 pmol\/mg, respectively (from 1.84 \u00b1 0.18 and 1.48 \u00b1 0.12 pmol\/mg at baseline), by week 1, when aneurysms developed. Oral folic acid administration, which has been shown to improve aortic H<jats:sub>4<\/jats:sub>B levels to completely prevent or markedly decrease the incidence of AAA, significantly increased tissue and plasma H<jats:sub>4<\/jats:sub>B levels in both animal models starting at week 1. The two H<jats:sub>4<\/jats:sub>B measurements at all conditions showed significant linear correlation, suggesting that plasma H<jats:sub>4<\/jats:sub>B accurately predicts its tissue levels when H<jats:sub>4<\/jats:sub>B is either reduced or enhanced. Together, these data demonstrate that H<jats:sub>4<\/jats:sub>B levels decrease with AAA development and increase with folic acid treatment in two different murine models of AAA and that plasma H<jats:sub>4<\/jats:sub>B levels accurately reflect H<jats:sub>4<\/jats:sub>B levels in the tissue, suggesting that circulating H<jats:sub>4<\/jats:sub>B levels may be used clinically as a novel and powerful biomarker for the development and response to treatment of AAA.<\/jats:p>","DOI":"10.1152\/ajpheart.00444.2014","type":"journal-article","created":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T03:29:48Z","timestamp":1411788588000},"page":"H1559-H1564","source":"Crossref","is-referenced-by-count":13,"title":["Circulating tetrahydrobiopterin as a novel biomarker for abdominal aortic aneurysm"],"prefix":"10.1152","volume":"307","author":[{"given":"Kin Lung","family":"Siu","sequence":"first","affiliation":[{"name":"Divisions of Molecular Medicine and Cardiology, Departments of 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