Significance of serum Zn-α2-glycoprotein for the regulation of blood pressure

• Published in: Hypertension research Vol. 38; no. 4; pp. 244 - 251
• Main Authors: Kurita, Souichi, Takeuchi, Keisuke, Hayashi, Yoshimi, Ueyama, Hisao, Zankov, Dimitar P, Pang, Xiaoling, Otsuka, Takanobu, Ohkubo, Iwao, Ogikubo, Osamu, Ogita, Hisakazu
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.04.2015
• Subjects: Adolescent; Adult; Aged; Animals; Blood pressure; Blood Pressure - genetics; Blood Pressure - physiology; Cell Line; Female; Gene expression; Gene Expression Regulation; Gene Knockdown Techniques; Glycoproteins; Humans; Hypertension; Hypertension - genetics; Hypertension - physiopathology; Male; Metabolic Syndrome - blood; Metabolism; Middle Aged; Muscle Tonus - genetics; Promoter Regions, Genetic - genetics; Rats; rhoA GTP-Binding Protein - genetics; rhoA GTP-Binding Protein - metabolism; Seminal Plasma Proteins - biosynthesis; Seminal Plasma Proteins - blood; Seminal Plasma Proteins - genetics; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - physiology; Young Adult
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/hr.2014.165

Zn-α2-glycoprotein (ZAG) (molecular weight=41 kDa) is one component in the α2 fraction of human plasma, and is reported to be associated with several diseases, such as cancers and metabolic syndromes. ZAG is also considered to be an important modulator of lipid metabolism. However, little is known about the correlation of serum ZAG levels with indicators of metabolic syndrome. Serum ZAG concentrations analyzed by enzyme-linked immunoassay were positively correlated with systolic and diastolic blood pressure in 326 subjects (236 males and 90 females) aged 17-79 years who had an annual health examination. By luciferase reporter and electrophoretic mobility shift assays, the core promoter region to regulate the ZAG gene expression was found to exist between -110 and -101. The transcription factor Sp1 interacted with this region, and Sp1 knockdown experiments showed that Sp1 critically regulated ZAG expression. Furthermore, ZAG increased the active form of RhoA, which was determined by pull-down assay. Increased serum ZAG concentrations induced, at least partly, by Sp1 may cause an increase in vascular tone through the activation of RhoA and contribute to elevated blood pressure.