The recently identified endogenous peptide apelin and its specific apelin receptor (APJ) are currently being considered as potential regulators in vascular tissue. Previously, we reported apelin mediates phosphorylation of myosin light chain and elicits vasoconstriction in vascular smooth muscle. In this study, physiological roles of the apelin-APJ system were investigated on atherosclerosis. In APJ and apolipoprotein E double-knockout (APJ ؊/؊ ApoE ؊/؊ ) mice fed a high-cholesterol diet, atherosclerotic lesions were dramatically reduced when compared with APJ Apelin receptor (APJ) is a G-protein-coupled receptor with seven transmembrane domains, and its endogenous ligand, apelin has been recently identified.1,2 The structures of APJ and apelin are highly conserved among species, and both are highly expressed in the cardiovascular system. 3,4 In the vascular system, APJ and apelin are known to be expressed in endothelium and vascular smooth muscle cells (VSMCs). Histological studies in rat show that the VSMCs of the medial layer of the aorta and pulmonary artery display intense staining for APJ-like immunoreactivity. 4 The vascular actions of apelin-APJ system may be complex. Under physiological conditions, the apelin-APJ system shows transient hypotension. The baseline blood pressure of APJ and angiotensin-type 1 receptor doubleknockout mice was significantly elevated compared with that of angiotensin-type 1 receptor knockout mice, 5 although APJ knockout (APJ Ϫ/Ϫ ) mice did not show any significant changes in cardiovascular parameters. In spontaneously hypertensive rats, APJ and apelin expression in both heart and aorta were markedly depressed compared with Wistar-Kyoto rats. 6 In aortae from type 2 diabetic db/db mice, APJ and apelin expression were

No abstract

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of TG-rich lipoproteins. To elucidate the physiological roles of LPL in lipid and lipoprotein metabolism, we generated transgenic rabbits expressing human LPL. In postheparinized plasma of transgenic rabbits, the human LPL protein levels were about 650 ng/ml, and LPL enzymatic activity was found at levels up to 4-fold greater than that in nontransgenic littermates. Increased LPL activity in transgenic rabbits was associated with as much as an 80% decrease in plasma triglycerides and a 59% decrease in high density lipoprotein-cholesterol. Analysis of the lipoprotein density fractions revealed that increased expression of the LPL transgene resulted in a remarkable reduction in the level of very low density lipoproteins as well as in the level of intermediate density lipoproteins. In addition, LDL cholesterol levels in transgenic rabbits were significantly increased. When transgenic rabbits were fed a cholesterol-rich diet, the development of hypercholesterolemia and aortic atherosclerosis was dramatically suppressed in transgenic rabbits. These results demonstrate that systemically increased LPL activity functions in the metabolism of all classes of lipoproteins, thereby playing a crucial role in plasma triglyceride hydrolysis and lipoprotein conversion, and that overexpression of LPL protects against diet-induced hypercholesterolemia and atherosclerosis. Lipoprotein lipase (LPL)1 plays a crucial role in lipid metabolism and transport by catalyzing the hydrolysis of triglyceriderich (TG-rich) lipoproteins such as chylomicrons and very low density lipoproteins (VLDL). Through the hydrolysis of TG in these particles, LPL converts these lipoproteins to denser lipoproteins such as chylomicron remnants, intermediate density lipoprotein (IDL), and low density lipoproteins (LDL) (1-3). This process generates free fatty acids (FFA), which are taken up and used for metabolic energy or stored as TG after reesterification and also results in the generation of surface remnants, which give rise to high density lipoproteins (HDL). It has been suggested that LPL influences not only plasma TG levels but also plasma HDL levels (4).LPL is mainly produced by mesenchymal cells such as adipose and muscle cells and then transported to the luminal surface of the vascular endothelium, where it is bound to heparan sulfate proteoglycans (HSPG). Small amounts of LPL are also present in other types of tissues, including the adrenals, brain, lung, and spleen (5). Furthermore, LPL is also expressed by macrophages and smooth muscle cells in atherosclerotic lesions (6, 7), suggesting that LPL modulates vascular functions and may be involved in atherogenesis. Elucidation of the precise roles of LPL in atherosclerosis has been compounded by the fact that LPL has multiple functions in lipoprotein metabolism through its catalytic properties and acts as a ligand for the LDL receptor-related protein (8) or a bridge between lipoproteins and HSPG (9). In humans, it has been found that familial L...

No abstract