Diminished expression of dihydropteridine reductase is a potent biomarker for hypertensive vessels.
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 1alpha, GSTomega1, 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.
Lee
Chang-Kwon
CK
Institute of Functional Genomics, School of Medicine, Konkuk University, Danwol-dong, Choonju, Korea.
Han
Jin Soo
JS
Won
Kyung-Jong
KJ
Jung
Seung-Hyo
SH
Park
Hyo-Jun
HJ
Lee
Hwan Myung
HM
Kim
Junghwan
J
Park
Young Shik
YS
Kim
Hyun-Jung
HJ
Park
Pyo-Jam
PJ
Park
Tae-Kyu
TK
Kim
Bokyung
B
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000201:enzymology*; D015415:Biomarkers / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D001794:Blood Pressure; D004093:Dihydropteridine Reductase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000201:enzymology*; D040901:Proteomics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D015415:Biomarkers; D001708:Biopterins; D004093:Dihydropteridine Reductase; C003402:sapropterin