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Kruppel Like Factor 15 is a Critical Regulator of Angiotensin II Mediated Vascular Remodeling
Author(s) -
Lu Yuan,
Haldar Saptarsi,
Hao Caili,
Cui Yingjie,
Doughman Yongqiu,
Watanabe Michiko,
Jain Mukesh K
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.637.7
Subject(s) - angiotensin ii , vascular remodelling in the embryo , vascular smooth muscle , medicine , mef2 , endocrinology , inflammation , microbiology and biotechnology , transcription factor , chemistry , biology , biochemistry , gene , receptor , enhancer , smooth muscle
Kruppel Like Factor 15 (KLF15) is a transcription factor expressed in smooth muscle (VSMC) from a diverse array of vascular beds. However, the functions of KLF15 in VSMC are poorly understood. The aim of this study was to study the role of KLF15 in Angiotensin II (Ang II) mediated vascular remodeling. We employed a model in which Ang II was infused via subcutaneous osmotic minipumps at 1440ug/kg/day for 2 weeks in wild type (WT) and KLF15‐/‐ mice (age 10‐12 weeks). KLF15 expression was significantly reduced in the thoracic aorta (TA) of WT mice stimulated with Ang II. While WT mice developed aortic medial hypertrophy and perivascular fibrosis in response to Ang II, KLF15 ‐/‐ mice developed a severe degenerative aortopathy characterized by gross outward remodeling, excessive vascular inflammation, elastin lamellar disruption, reactive oxygen specious (ROS) accumulation, and apoptotic SMC loss. KLF15 ‐/‐ aorta have exaggerated expression of monocyte chemoattractant protein‐1(MCP‐1) and matrix metalloproteinase‐3 (MMP3) as well as exaggerated accumulation of p53 and its target genes (p21, bax). Promoter and ChIP studies demonstrate that KLF15 can inhibit MEF2 activity and its occupancy of the MCP‐1 promoter. Our results support a critical role for KLF15 in the regulation of Ang II mediated vascular inflammation and remodeling. Supported by NIH R01HL084154