Abstract 1666: Endothelial Lipase Modulates Lesion Formation in Mouse Model of Vascular Remodeling
Background - Endothelial lipase (EL) is expressed by vascular endothelial cells, and plays an important role in HDL metabolism. EL is also expressed by infiltrating macrophages and smooth muscle cells (SMCs) in human atherosclerotic lesions. Besides the enzymatic action on HDL-phospholipids, EL is known to have a non-enzymatic bridging function between endothelial cells and lipoproteins or circulating monocytes. These findings suggest that EL plays a role in the progression of vascular diseases. To clarify the role of EL in vascular remodeling, a carotid ligation model was employed using EL-knockout (EL-KO) and human EL-transgenic (EL-Tg) mice.
Method and Results- The common carotid artery was ligated at the just proximal site of the carotid bifurcation. Two or four weeks later, the common carotid artery was excised and the lesion area was measured. Histological studies revealed that diffuse medial thickening and neointimal formation were observed in the carotid arteries, while the endothelium remained uninjured. Interestingly, the neointimal lesion area was significantly decreased in EL-KO mice (1.31±0.76x104microm2 ;n=9 vs. 5.33±0.71x104microm2 ;n=10, P<0.05) and increased in EL-transgenic mice (6.84±0.80 x104 microm2 ;n=14, vs. 3.89±0.96x104 microm2 ;n=10, P<0.05), compared with wild-type mice. The neointimal lesion was mainly positive for the smooth muscle cell marker, suggesting that EL levels in the vessel wall were associated with increased smooth muscle content. Overexpression of human EL in rat SMC by adenovirus vector produced increases cell migration but no influence in cell proliferation. Oxidative stress of the lesion was reduced in EL-KO mice (dihydroethidium method and lucigenin method)and expression of adhision molecule such as ICAM-1 was decreased in EL-KO mice.
Conclusions- EL plays a role in the development of vascular remodeling through modulating smooth muscle migration and local inflammation.