Vascular-protective effects of high-density lipoprotein include the downregulation of the angiotensin II type 1 receptor

Van Linthout, S., Spillmann, F., Lorenz, M., Meloni, M., Jacobs, F., Egorova, M., Stangl, V., De Geest, B., Schultheiss, H.-P. and Tschope, C. (2009) Vascular-protective effects of high-density lipoprotein include the downregulation of the angiotensin II type 1 receptor. Hypertension, 53(4), pp. 682-687. (doi: 10.1161/HYPERTENSIONAHA.108.118919)

Abstract

There is growing evidence that a cross-talk exists between the renin-angiotensin (Ang) system and lipoproteins. We investigated the role of high-density lipoprotein (HDL) on Ang II type 1 receptor (AT1R) regulation and subsequent Ang II–mediated signaling under diabetic conditions. To investigate the effect of HDL on AT1R expression in vivo, apolipoprotein A-I gene transfer was performed 5 days after streptozotocin injection. Six weeks after apolipoprotein A-I gene transfer, the 1.9-fold (P=0.001) increase of HDL cholesterol was associated with a 4.7-fold (P<0.05) reduction in diabetes mellitus–induced aortic AT1R expression. Concomitantly, NAD(P)H oxidase activity, Nox 4, and p22^phox mRNA expression were reduced 2.6-fold, 2.0-fold, and 1.5-fold (P<0.05), respectively, whereas endothelial NO synthase dimerization was increased 3.3-fold (P<0.005). Apolipoprotein A-I transfer improved NO bioavailability as indicated by ameliorated acetylcholine-dependent vasodilation in the streptozotocin-Ad.hapoA-I group compared with streptozotocin-induced diabetes mellitus. In vitro, HDL reduced the hyperglycemia-induced upregulation of the AT1R in human aortic endothelial cells. This was associated with a 1.3-fold and 2.2-fold decreases in reactive oxygen species and NAD(P)H oxidase activity, respectively (P<0.05). Finally, HDL reduced the responsiveness to Ang II, as indicated by decreased oxidative stress in the hyperglycemia+HDL+Ang II group compared with the hyperglycemia+Ang II group. In conclusion, vascular-protective effects of HDL include the downregulation of the AT1R.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Meloni, Dr Marco
• Authors: Van Linthout, S., Spillmann, F., Lorenz, M., Meloni, M., Jacobs, F., Egorova, M., Stangl, V., De Geest, B., Schultheiss, H.-P., and Tschope, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• Publisher: American Heart Association
• ISSN: 0194-911X
• ISSN (Online): 1524-4563