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Deficiency of Receptor-associated Protein Attenuates Angiotensin II-induced Atherosclerosis in Hypercholesterolemic Mice Without Influencing Abdominal Aortic ...

S Wang, V Subramanian, H Lu, DA Howatt... - Atherosclerosis, 2011 - Elsevier Objective Receptor-associated protein (RAP) was initially described as a regulator of low density lipoprotein receptor-related protein 1 (LRP1), but is now known to regulate many proteins. Since the direct effects of RAP on vascular pathologies have not been studied, ...

Receptor-associated protein (RAP) was initially described as a regulator of low density lipoprotein receptor-related protein 1 (LRP1), but is now known to regulate many proteins. Since the direct effects of RAP on vascular pathologies have not been studied, this study determined whether RAP deficiency influenced angiotensin II (Ang II)-induced atherosclerosis and abdominal aortic aneurysms (AA As) in hypercholesterolemic mice.

Male LDL receptor / mice that were either RAP +/+ or / were infused with Ang II (500 ng/kg/min) for 4 weeks while consuming a saturated fat-enriched diet. RAP deficiency had no effects on body weight or Ang II-induced increases of systolic blood pressure. Despite increased plasma cholesterol concentrations, RAP deficiency reduced atherosclerotic lesion size in aortic arches, while having no effect on Ang II-induced AA As. RAP deficiency profoundly reduced LRP1 protein abundance in macrophages, but did not change its abundance in aortic smooth muscle cells. Also, RAP deficiency had no effects on m RNA abundance of LRP1 or lipoprotein lipase in macrophages. To determine whether RAP deficiency in leukocytes influenced Ang II-induced atherosclerosis, irradiated male LDL receptor / mice were repopulated with bone marrow-derived cells from either RAP +/+ or / male mice. The chimeric mice were infused with Ang II (500 ng/kg/min) for 4 weeks while fed the saturated fat-enriched diet. RAP deficiency in bone marrow-derived cells did not influence either plasma cholesterol concentrations or atherosclerotic lesion size.