gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Increased High Density Lipoprotein Cholesterol induced by Human Apolipoprotein A-I Gene Transfer Improves Left Ventricular Function in an Experimental Model of Diabetic Cardiopathy

Humaner Apolipoprotein A-I Gentransfer erhöht High-Density-Lipoprotein-Cholesterin-Spiegel und verbessert die linksventrikuläre Funktion in einem experimentellen Modell der diabetischen Kardiopathie

Meeting Abstract

  • S. van Linthout - Charité - Universitätsmedizin Berlin, Campus Benjamin Granklin, Berlin (Berlin, D)
  • A. Riad - Charité - Universitätsmedizin Berlin, Campus Benjamin Granklin, Berlin (Berlin, D)
  • J. Lievens - Charité - Universitätsmedizin Berlin, Campus Benjamin Granklin, Berlin (Berlin, D)
  • B. de Geest - Charité - Universitätsmedizin Berlin, Campus Benjamin Granklin, Berlin (Berlin, D)
  • H.P. Schultheiss - Charité - Universitätsmedizin Berlin, Campus Benjamin Granklin, Berlin (Berlin, D)
  • C. Tschöpe - Charité - Universitätsmedizin Berlin, Campus Benjamin Granklin, Berlin (Berlin, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP141

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch141.shtml

Veröffentlicht: 8. August 2006

© 2006 van Linthout et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: Diabetes mellitus is associated with the development of a specific cardiopathy, which is partly due to intramyocardial inflammation and endothelial dysfunction. Given the known anti-inflammatory and endothelial-protective potential of high density lipoproteins (HDL), we evaluated the hypothesis that gene transfer (GT) with human apolipoprotein (apo) A-I, the principal apo of HDL, improves left ventricular (LV) function in an experimental model of diabetic cardiopathy.

Methods: DM was induced by a single injection of streptozotocin (STZ; 70 mg/kg, i.p.) in 8 weeks (w) old Sprague Dawley (SD) rats. Intravenous GT was performed 5 days after STZ injection with 3 x 1012 particles of the E1E3E4-deleted vector Ad.hapoA-I, expressing human apo A-I, or of Ad.Null, containing no expression cassette. Age-matched non-diabetic SD rats injected with the same dose of Ad.Null were used as controls. LV mRNA levels of intracellular adhesion molecule (ICAM)-I, vascular adhesion molecule (VCAM)-I, tumor necrosis factor (TNF)-? and advanced glycation endproduct receptor (AGER) were determined by real time RT-PCR. Phosphorylated (p) and total (tot.) p38 mitogen activated protein kinase (MAPK) and Akt were analyzed by Western Blot.

Results: Ad.hapo A-I induced sustained human apo A-I expression and increased HDL cholesterol (C) for the entire duration of the experiment, 6w. Human apo A-I peak expression was associated with a 1.7-fold (p<0.05) increase of HDL-C levels. LV function analysis assessed by a Millar conductance catheter, performed 6w after GT, documented an improvement in LV function in the STZ-Ad.hapo A-I group compared to the STZ-Ad.Null group.

LV mRNA levels of ICAM-I, VCAM-I, TNF-? and AGER were reduced by 1.8-fold (p<0.05), 2.4-fold (p<0.005), 4.5-fold (p<0.05) and 1.9-fold (p<0.05), respectively, in STZ-Ad.hapo A-I rats compared to Ad.Null injected diabetic rats. Western blot analysis showed that the ratio of p-p38MAPK/tot.- p38MAPK was 1.8-fold (p<0.05) lower in STZ-Ad.hapo A-I than in STZ-Ad.Null rats. In contrast, the ratio of p-Akt/tot.-Akt was 2.1-fold (p<0.05) induced in the STZ-Ad.hapo A-I compared to the STZ-Ad.Null group.

Conclusion: In conclusion, human apo A-I GT reduces diabetes-associated cardiac inflammation, resulting in an improved LV function.