Novel role of proline-rich nonreceptor tyrosine kinase 2 in vascular wall remodeling after balloon injury

Ravisekhar Gadepalli, Nikhlesh Singh, Venkatesh Kundumani-Sridharan, Mark R. Heckle, Rao Gadiparthi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objective-To investigate the role of Pyk2, a proline-rich nonreceptor tyrosine kinase, in G protein-coupled receptor agonist, thrombin-induced human aortic smooth muscle cell growth and migration, and injury-induced vascular wall remodeling. Methods and Results-Thrombin, a G protein-coupled receptor agonist, activated Pyk2 in a time-dependent manner and inhibition of its stimulation attenuated thrombin-induced human aortic smooth muscle cell migration and proliferation. Thrombin also activated Grb2-associated binder protein 1, p115 Rho guanine nucleotide exchange factor, Rac1, RhoA, and p21-activated kinase 1 (Pak1) and interference with stimulation of these molecules attenuated thrombin-induced human aortic smooth muscle cell migration and proliferation. In addition, adenovirus-mediated expression of dominant negative Pyk2 inhibited thrombin-induced Grb2-associated binder protein 1, p115 rho guanine nucleotide exchange factor, Rac1, RhoA and Pak1 stimulation. Balloon injury also caused activation of Pyk2, Grb2-associated binder protein 1, p115 rho guanine nucleotide exchange factor, Rac1, RhoA, and Pak1 in the carotid artery of rat, and these responses were sensitive to inhibition by the dominant negative Pyk2. Furthermore, inhibition of Pyk2 activation resulted in reduced recruitment of smooth muscle cells onto the luminal surface and their proliferation in the intimal region leading to suppression of neointima formation. Conclusion-Together, these results demonstrate for the first time that Pyk2 plays a crucial role in G protein-coupled receptor agonist thrombin-induced human aortic smooth muscle cell growth and migration, as well as balloon injury-induced neointima formation.

Original languageEnglish (US)
Pages (from-to)2652-2661
Number of pages10
JournalArteriosclerosis, thrombosis, and vascular biology
Volume32
Issue number11
DOIs
StatePublished - Nov 1 2012

Fingerprint

Focal Adhesion Kinase 2
Rho Guanine Nucleotide Exchange Factors
Thrombin
Smooth Muscle Myocytes
p21-Activated Kinases
Wounds and Injuries
Cell Movement
G-Protein-Coupled Receptors
Neointima
Cell Proliferation
Tunica Intima
Proteins
Growth
Vascular Remodeling
Carotid Arteries
Proline
Adenoviridae
Protein-Tyrosine Kinases

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Novel role of proline-rich nonreceptor tyrosine kinase 2 in vascular wall remodeling after balloon injury. / Gadepalli, Ravisekhar; Singh, Nikhlesh; Kundumani-Sridharan, Venkatesh; Heckle, Mark R.; Gadiparthi, Rao.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 32, No. 11, 01.11.2012, p. 2652-2661.

Research output: Contribution to journalArticle

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