Published Online
on March 9, 2009

A more recent version of this article appeared on April 1, 2009

This Article Full Text (PDF) Data Supplement All Versions of this Article: 53/4/682    most recent HYPERTENSIONAHA.108.118919v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Van Linthout, S. Articles by Tschöpe, C. Search for Related Content PubMed PubMed Citation Articles by Van Linthout, S. Articles by Tschöpe, C. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Related Collections ACE/Angiotension receptors Other diabetes Gene therapy Related Article

Submitted on July 2, 2008
Revised on July 23, 2008

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; and 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.

^* To whom correspondence should be addressed. E-mail: carsten.tschoepe{at}charite.de.

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.

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

Related Article:

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]