EXPRESSION OF VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR MESSENGER-RNA IN RABBIT ATHEROSCLEROTIC LESIONS

The expression of very low density lipoprotein (VLDL) receptor mRNA in atherosclerotic lesions in rabbits was investigated. To examine the e xpression of the VLDL receptor in the vascular wall, poly(A)(+) RNA wa s isolated from whole aortas of cholesterol-fed New Zealand White (NZW ), Watanabe heritable hyperlipidemic (WHHL), and normal NZW rabbits, a nd then Northern blot analysis was performed. The VLDL receptor mRNA w as detected in aortas from both NZW rabbits fed 0.5% cholesterol for 1 6 weeks and 12-month-old WHHL rabbits, whereas no expression was seen in normal NZW rabbit aortas. To further determine the localization of the VLDL receptor mRNA, in situ hybridization using digoxigenin-labele d riboprobes and immunohistochemistry using monoclonal antibodies agai nst each cell component were performed Early atherosclerotic lesions, termed fatty streaks, in the NZW rabbits fed 0.5% cholesterol for 4 we eks demonstrated strong expression of the VLDL receptor mRNA by macrop hages, The VLDL receptor mRNA was also expressed in more advanced athe rosclerotic lesions from both atherogenic animal models. The Predomina nt origin of the VLDL receptor mRNA-positive cells was macrophages, an d some intimal smooth muscle cells appeared to express a weak but sign ificant signal in these advanced lesions, Our findings suggest that th e VLDL receptor expression may play a role in the development of ather osclerosis.