Hypertension promotes phosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 in rats: Implication for the pathogenesis of hypertensive vascular disease

Koichiro Sugimura, Yoshihiro Fukumoto, Jun Nawata, Huan Wang, Noriko Onoue, Tomohiro Tada, Kunio Shirato, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Atherosclerosis is initiated by adhesion and infiltration of inflammatory leukocytes into the intima, where non-receptor protein tyrosine kinases, such as focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2), play important roles as intracellular messengers of mechanical and biochemical signals. In the present study, we examined whether FAK and PYK2 are up-regulated by elevated blood pressure or circulating humoral factors in hypertension. We used a rat model of abdominal aortic banding that allows separate evaluation of elevated blood pressure (upper body) and circulating humoral factors (lower body). We obtained the proximal and distal aortas of the banding site, 6 hours, 3 days, and 1 and 4 weeks after the banding procedure, for evaluation of phosphorylation of FAK and PYK2 by Western blotting. Arterial pressure was significantly elevated only in the upper body throughout the experimental period. The expression of FAK and the FAK phosphorylation were significantly increased at 1 and 4 weeks only in the proximal aorta. This was also the case for the expression of total PYK2 and the PYK2 phosphorylation. In contrast, there was no significant change in FAK or PYK2 phosphorylation in the distal aorta, whereas plasma levels of angiotensin II were systemically elevated. In sham-operated rats, no change in FAK or PYK2 phoshorylation was noted in the proximal and distal aortas. These results indicate that phosphorylation of FAK and PYK2 is upregulated by elevated blood pressure but not by humoral factors in the rat aorta, demonstrating novel aspects of atherogenesis in hypertension.

Original languageEnglish
Pages (from-to)201-210
Number of pages10
JournalTohoku Journal of Experimental Medicine
Volume222
Issue number3
DOIs
Publication statusPublished - 2010

Keywords

  • Angiotensin ii
  • Focal adhesion kinase
  • Humoral factors
  • Integrins
  • Proline-rich tyrosine kinase 2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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