Journal
HYPERTENSION
Volume 55, Issue 1, Pages 161-165Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.109.143057
Keywords
angiotensin II; platelet-derived factor; signal transduction; arterial injury; restenosis
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL076770, R01HL063810, R01HL077726, K01HL076575, R01HL090885] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01 HL076770-05A2, R01 HL090885, R01 HL076770, K01 HL076575, HL063810, R01 HL090885-02, R01 HL076770-04, R01 HL077726, HL076770, HL090885, HL076575, R01 HL063810] Funding Source: Medline
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Vascular smooth muscle cell hypertrophy, proliferation, or migration occurs in hypertension, atherosclerosis, and restenosis after angioplasty, leading to pathophysiological vascular remodeling. Angiotensin II and platelet-derived growth factor are well-known participants of vascular remodeling and activate a myriad of downstream protein kinases, including p21-activated protein kinase (PAK1). PAK1, an effector kinase of small GTPases, phosphorylates several substrates to regulate cytoskeletal reorganization. However, the exact role of PAK1 activation in vascular remodeling remains to be elucidated. Here, we have hypothesized that PAK1 is a critical target of intervention for the prevention of vascular remodeling. Adenoviral expression of dominant-negative PAK1 inhibited angiotensin II-stimulated vascular smooth muscle cell migration. It also inhibited vascular smooth muscle cell proliferation induced by platelet-derived growth factor. PAK1 was activated in neointima of the carotid artery after balloon injury in the rat. Moreover, marked inhibition of the neointima hyperplasia was observed in a dominant-negative PAK1 adenovirus-treated carotid artery after the balloon injury. Taken together, these results suggest that PAK1 is involved in both angiotensin II and platelet-derived growth factor-mediated vascular smooth muscle cell remodeling, and inactivation of PAK1 in vivo could be effective in preventing pathophysiological vascular remodeling. (Hypertension. 2010; 55: 161-165.)
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