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(Hypertension. 2009;53:682.)
© 2009 American Heart Association, Inc.

Original Articles

Vascular-Protective Effects of High-Density Lipoprotein Include the Downregulation of the Angiotensin II Type 1 Receptor

Sophie Van Linthout; Frank Spillmann; Mario Lorenz; Marco Meloni; Frank Jacobs; Marina Egorova; Verena Stangl; Bart De Geest; Heinz-Peter Schultheiss; Carsten Tschöpe

From the Department of Cardiology and Pneumology (S.V.L., F.S., M.M., M.E., H.-P.S., C.T.), Charité–University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany; Department of Cardiology and Angiology (M.L., V.S.), Charité–University Medicine Berlin, Campus Mitte, Berlin, Germany; and the Center for Molecular and Vascular Biology (F.J., B.D.G.), University of Leuven, Leuven, Belgium.

Correspondence to Carsten Tschöpe, Department of Cardiology and Pneumology, Charité–University Medicine of Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail carsten.tschoepe{at}charite.de

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.

Key Words: high-density lipoprotein • angiotensin AT1 receptor • endothelial function • diabetes mellitus

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From Menace to Marvel: High-Density Lipoprotein Prevents Endothelial Nitric Oxide Synthase Uncoupling in Diabetes Mellitus by Angiotensin II Type 1 Receptor Downregulation

Philip Wenzel and Thomas Münzel
Hypertension 2009 53: 587-589. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				P. Wenzel and T. Munzel From Menace to Marvel: High-Density Lipoprotein Prevents Endothelial Nitric Oxide Synthase Uncoupling in Diabetes Mellitus by Angiotensin II Type 1 Receptor Downregulation Hypertension, April 1, 2009; 53(4): 587 - 589. [Full Text] [PDF]