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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Am+J+Physiol+Heart+Circ+Physiol 2014 ; 307 (11): H1559-64 Nephropedia Template TP
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Circulating tetrahydrobiopterin as a novel biomarker for abdominal aortic aneurysm #MMPMID25260610
Siu KL; Cai H
Am J Physiol Heart Circ Physiol 2014[Dec]; 307 (11): H1559-64 PMID25260610show ga
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 (H4B) in angiotensin II-infused hyperphenylalaninemia (hph-1) and apoE null mice. For apoE null mice, tissue and plasma H4B levels decreased time dependently, to 2.69 ± 0.15 and 1.99 ± 0.06 pmol/mg, respectively (from 4.86 ± 0.32 and 3.31 ± 0.13 pmol/mg at baseline) by week 3, when aneurysms developed. For hph-1 mice, tissue and plasma H4B levels decreased significantly to 1.02 ± 0.10 and 0.98 ± 0.09 pmol/mg, respectively (from 1.84 ± 0.18 and 1.48 ± 0.12 pmol/mg at baseline), by week 1, when aneurysms developed. Oral folic acid administration, which has been shown to improve aortic H4B levels to completely prevent or markedly decrease the incidence of AAA, significantly increased tissue and plasma H4B levels in both animal models starting at week 1. The two H4B measurements at all conditions showed significant linear correlation, suggesting that plasma H4B accurately predicts its tissue levels when H4B is either reduced or enhanced. Together, these data demonstrate that H4B levels decrease with AAA development and increase with folic acid treatment in two different murine models of AAA and that plasma H4B levels accurately reflect H4B levels in the tissue, suggesting that circulating H4B levels may be used clinically as a novel and powerful biomarker for the development and response to treatment of AAA.