This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Stulnig, T. M. Articles by Wick, G. Search for Related Content PubMed PubMed Citation Articles by Stulnig, T. M. Articles by Wick, G.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:872-878.)
© 1995 American Heart Association, Inc.

Articles

In Vivo LDL Receptor and HMG-CoA Reductase Regulation in Human Lymphocytes and Its Alterations During Aging

Thomas M. Stulnig; Helmut Klocker; H. James Harwood, Jr; Günther Jürgens; Dieter Schönitzer; Elmar Jarosch; Lukas A. Huber; Albert Amberger; Georg Wick

From the Institute for General and Experimental Pathology, University of Innsbruck (Austria) (T.M.S., L.A.H., G.W.); the Clinic for Urology, University Clinics Innsbruck (Austria) (H.K.); the Department of Metabolic Diseases, Pfizer Central Research, Groton, Conn (H.J.H.); the Institute for Medical Biochemistry, University of Graz (Austria) (G.J.); the Blood Transfusion Unit (D.S.) and the Central Laboratory for Medical and Chemical Laboratory Diagnosis (E.J.), University Clinics Innsbruck and the Institute for Biomedical Aging Research, Austrian Academy of Sciences (A.A., G.W.), Innsbruck, Austria.

Correspondence to Prof Dr G. Wick, Institute for General and Experimental Pathology, University of Innsbruck, Fritz-Pregl-Str 3/4, A-6020 Innsbruck, Austria.

Abstract The LDL receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase play primary roles in the regulation of cellular cholesterol metabolism. To investigate the transcriptional regulation of lipid metabolism under physiological conditions ex vivo and its alterations during aging, we analyzed both the activity and mRNA concentration of the LDL receptor and HMG-CoA reductase in freshly isolated lymphocytes from healthy young and elderly donors. Data from fluorescent reverse transcriptase–polymerase chain reaction indicated that not only plasma LDL but also plasma HDL downregulates lymphocyte LDL receptor mRNA. Downregulation by HDL was three times more effective than that by LDL and presumably involved specific HDL binding sites. There was coordinate regulation of HMG-CoA reductase mRNA with LDL receptor mRNA that was independent of plasma lipoprotein concentrations. Despite elevated plasma concentrations of LDL, lymphocytes from elderly donors paradoxically expressed increased levels of the LDL receptor (P=.030) and HMG-CoA reductase mRNA (P=.062). The age-related dysregulation of the LDL receptor was predominantly due to impaired downregulation by plasma LDL rather than by HDL. Thus, not only LDL but also HDL and age significantly influences the transcriptional regulation of the LDL receptor in extrahepatic cells in vivo.

Key Words: aging • hydroxymethylglutaryl coenzyme A reductase • transcriptional regulation • LDL receptor • HDL receptor

This article has been cited by other articles:

				T. M. STULNIG, M. BERGER, M. RODEN, H. STINGL, D. RAEDERSTORFF, and W. WALDHÄUSL Elevated serum free fatty acid concentrations inhibit T lymphocyte signaling FASEB J, May 1, 2000; 14(7): 939 - 947. [Abstract] [Full Text]