Biomechanically Induced Gene iex-1 Inhibits Vascular Smooth Muscle Cell Proliferation and Neointima Formation

• Published in: Circulation research 2003-12, Vol.93 (12), p.1210-1217
• Main Authors: Schulze, P Christian, de Keulenaer, Gilles W, Kassik, Kimberly A, Takahashi, Tomosaburo, Chen, Zhiping, Simon, Daniel I, Lee, Richard T
• Format: Article
• Language: English
• Subjects: Animals; Apolipoproteins E - genetics; Apoptosis Regulatory Proteins; Arteriosclerosis - genetics; Arteriosclerosis - physiopathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Carotid Artery Injuries - genetics; Carotid Artery Injuries - physiopathology; Cell Cycle - physiology; Cell Division - physiology; Cells, Cultured; Gene Expression Regulation; Green Fluorescent Proteins; Humans; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Mechanotransduction, Cellular - physiology; Medical sciences; Membrane Proteins; Mice; Mice, Knockout; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; NF-kappa B - metabolism; Receptors, LDL - genetics; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stress, Mechanical; Tunica Intima - physiopathology
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.0000103635.38096.2F

ABSTRACT—Mechanotransduction plays a prominent role in vascular pathophysiology but is incompletely understood. In this study, we report the biomechanical induction of the immediate early response gene iex-1 in vascular smooth muscle cells (SMCs). Mechanical induction of iex-1 was confirmed by Northern (30-fold induction after 2 hours) and Western (6-fold induction after 24 hours) analyses. Expression of iex-1 was regulated by mechanical activation of nuclear factor (NF)-κB and abolished by overexpression of IκB in SMCs. The function of iex-1 in SMCs was explored by gene transfer using adenoviral vectors overexpressing iex-1. After 48 hours of 4% cyclic mechanical strain, adenoviral vectors overexpressing iex-1–infected cells had lower [H]-thymidine incorporation compared with AdGFP-infected controls (71.3±8.5% versus 180.2±19.4% in controls; P