Expression of Endothelial Lipase Correlates with the Size of Neointima in a Murine Model of Vascular Remodeling

• Published in: Journal of Atherosclerosis and Thrombosis 2012, Vol.19(12), pp.1110-1127
• Main Authors: Sun, Li, Ishida, Tatsuro, Okada, Takeaki, Yasuda, Tomoyuki, Hara, Tetsuya, Toh, Ryuji, Shinohara, Masakazu, Yamashita, Tomoya, Rikitake, Yoshiyuki, Hirata, Ken-ichi
• Format: Article
• Language: English
• Subjects: Angiotensin II - metabolism; Animals; Carotid Artery, Common - pathology; Cell Adhesion; Cell Movement; Cell Proliferation; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular - enzymology; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation, Enzymologic; HDL cholesterol; Humans; Inflammation; Lipase - biosynthesis; Lipoproteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocytes, Smooth Muscle - cytology; Neointima - pathology; Oxidative Stress; Proliferation; Vascular remodeling
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.13110

Aim: Endothelial lipase (EL) regulates plasma high-density lipoprotein-cholesterol (HDL-C) levels by promoting HDL catabolism. However, it remains unknown whether the inhibition of EL has beneficial effects on the genesis of vascular diseases. Here, we investigated the role of EL on vascular remodeling in mice. Methods: Vascular remodeling was developed by ligation of the left common carotid artery and neointimal lesions were histologically compared between EL-knockout (ELKO), EL-transgenic (ELTg), and wild-type (WT) mice. HDL was isolated from these mice, and effects of the HDL on cell growth and Erk activation were evaluated in vitro using cultured vascular smooth muscle cells. Results: Plasma HDL-C levels were 62% higher in ELKO and 13% lower in ELTg than in WT mice, after the carotid ligation. The size of neointimal lesion was significantly larger in ELTg and smaller in ELKO than in WT mice. Vascular expression of adhesion molecules was lower in ELKO and higher in ELTg compared with WT mice. Moreover, oxidative stress was attenuated in ELKO mice. HDL isolated from ELKO, ELTg, and WT mice inhibited expression of intercellular adhesion molecule-1, angiotensin II-induced activation of Erk, and growth of cultured vascular smooth muscle cells, whereas EL expression itself did not affect cell migration or growth. Conclusion: EL expression modulates vascular remodeling as well as plasma HDL-C levels. EL inactivation may increase HDL particles that can inhibit smooth muscle cell growth and migration.