Premium
Diminished expression of dihydropteridine reductase is a potent biomarker for hypertensive vessels
Author(s) -
Lee ChangKwon,
Han Jin Soo,
Won KyungJong,
Jung SeungHyo,
Park HyoJun,
Lee Hwan Myung,
Kim Junghwan,
Park Young Shik,
Kim HyunJung,
Park PyoJam,
Park TaeKyu,
Kim Bokyung
Publication year - 2009
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200800973
Subject(s) - tetrahydrobiopterin , endocrinology , medicine , downregulation and upregulation , gtp cyclohydrolase i , reductase , biopterin , vascular smooth muscle , enzyme , spontaneously hypertensive rat , contraction (grammar) , biology , chemistry , biochemistry , smooth muscle , blood pressure , nitric oxide synthase , nitric oxide , gene
To identify the new targets for hypertension, we analyzed the protein expression profiles of aortic smooth muscle in spontaneously hypertensive rats (SHR) of various ages during the development of hypertension, as well as in age‐matched normotensive Wistar–Kyoto (WKY) rats, using a proteomic analysis. The expressions of seven proteins were altered in SHR compared with WKY rats. Of these proteins, NADH dehydrogenase 1α, GSTω1, peroxi‐redoxin I and transgelin were upregulated in SHR compared with WKY rats. On the other hand, the expression of HSP27 and Ran protein decreased in SHR. The diminution of dihydrobiopterin reductase, an enzyme located in the regeneration pathways of tetrahydrobiopterin (BH4), was also prominent in SHR. The results from a PCR analysis revealed that the expression of BH4 biosynthesis enzymes – GTP cyclohydrolase‐1 and sepiapterin reductase – decreased and increased, respectively, in SHR compared with WKY rats. The level of BH4 was less in aortic strips from SHR than from WKY rats. Moreover, treatment with BH4 inhibited aortic smooth muscle contraction induced by serotonin. These results suggest that the deficiency in BH4 regeneration produced by diminished dihydrobiopterin reductase expression is involved in vascular disorders in hypertensive rats.