© 2000 American Heart Association, Inc.
Molecular Medicine |
Role of the JAK/STAT Pathway in Rat Carotid Artery Remodeling After Vascular Injury
From the Cardiovascular Research Institute (Y.S., H.K., R.S., T.N., T.I.), Kurume University, and Internal Medicine III, Kurume University School of Medicine (Y.S., H.K., R.S., T.N., T.I.), and Department of Molecular Genetics, Institute of Life Science (H.Y., A.Y.), Kurume University, Kurume, Japan.
Correspondence to Hisashi Kai, MD, PhD, The Cardiovascular Research Institute, Kurume University, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. E-mail naikai{at}med.kurume-u.ac.jp
Abstract—In cultured vascular smooth muscle cells (VSMCs), Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) are expressed constitutively and play a role in angiotensin II (Ang II)–induced intracellular signaling and proliferation. However, little is known regarding the relevance of these proteins to the process of vascular remodeling. The role of JAK and STAT proteins in vascular remodeling and their functional coupling with Ang II were examined in balloon-injured rat carotid artery. Immunoreactive Jak2, Tyk2, Stat1, and Stat3 were not detected in the intact artery. Immunohistostaining showed transient expressions of these JAKs and STATs in medial and neointimal VSMCs at days 2 and 5, respectively, with a peak at day 7 in both layers. The expressions declined to insignificant levels by day 14. Ang II type 1 receptors (AT1s) were coexpressed in the medial and neointimal VSMCs expressing Jak2 and Stat3. The Jak2 and Stat3 inductions in the injured artery were accompanied by constitutive Jak2 and Stat3 phosphorylations, which were enhanced by ex vivo Ang II stimulation via AT1. Additionally, a Jak2 inhibitor, AG490, blocked the Ang II–induced Stat3 phosphorylation. Furthermore, local treatment with AG490 inhibited constitutive Stat3 phosphorylation and neointimal VSMC replication and subsequently reduced neointima formation in the injured artery. In conclusion, JAK and STAT proteins were inducible in medial and neointimal VSMCs after vascular injury and were functionally coupled to AT1. The inductions of JAKs and STATs would be involved in the mechanisms of neointima formation after vascular injury. (Circ Res. 2000;87:12-18.)
Key Words: signal transduction • remodeling • arteries • muscle, smooth • angiotensin
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