Neuropeptides induced a pronounced and statin-sensitive dysregulation of mevalonate cycle in human monocytes of patients with hypercholesterolemia

Béla Kosztáczky, Gabriella Fóris, I. Seres, Zoltán Balogh, Péter Fülöp, Peter Koncsos, G. Paragh

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Angiotensin II (Ang II) and leptin generate statin-inhibitable superoxide anion production that accounts for only part of the entire superoxide anion production. In our recent studies, we aimed at elucidating whether Ang II and leptin, affecting the intensity of the mevalonate cycle, are able to increase endogenous cholesterol synthesis. Furthermore, we compared the superoxide anion and cholesterol production capability of monocytes of healthy control volunteers and monocytes obtained from patients with hypercholesterolemia (HC). We also studied the differences of the produced statin-inhibitable superoxide anion and cholesterol synthesis in control and HC-monocytes, depending on the applied stimulating ligands. In control and HC-monocytes - stimulated by Ang II, leptin, fenyl-Me-Leu-Phe (FMLP), phorbol-12-myristate-13-acetate (PMA) and A23187 - we determined the proportion of mevalonate cycle-dependent and -independent superoxide and cholesterol production, using lovastatin (Lov), and 25-hydroxycholesterol (25-HC). According to our results; (1) superoxide anion generation in HC-monocytes was elevated after Ang II, leptin and FMLP-stimulation, whereas PMA and A23187-stimulation had lower stimulating effect in HC than in control cells. (2) Cholesterol synthesis was increased only after stimulation with Ang II and leptin. (3) The Ang II and leptin-induced total superoxide anion generation and cholesterol synthesis were more elevated in HC than in control monocytes. (4) In contrast, the increase in Lov and 25-HC sensitive cholesterol synthesis were higher in resting, but lower in stimulated HC monocytes than in control cells. Summarizing our results, we concluded that Ang II and leptin are involved in enhancement of endogenous cholesterol synthesis through a statin-sensitive pathway.

Original languageEnglish
Pages (from-to)309-316
Number of pages8
JournalNeuropeptides
Volume40
Issue number5
DOIs
Publication statusPublished - Oct 2006

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Mevalonic Acid
Hypercholesterolemia
Neuropeptides
Leptin
Monocytes
Superoxides
Angiotensin II
Cholesterol
leucyl-phenylalanine
Lovastatin
Calcimycin
Acetates
Healthy Volunteers
Ligands

Keywords

  • Angiotensin II
  • Hypercholesterolemia
  • Leptin
  • Monocytes
  • Signal pathway
  • Superoxide anion

ASJC Scopus subject areas

  • Endocrinology
  • Clinical Neurology
  • Endocrinology, Diabetes and Metabolism
  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Biochemistry

Cite this

Neuropeptides induced a pronounced and statin-sensitive dysregulation of mevalonate cycle in human monocytes of patients with hypercholesterolemia. / Kosztáczky, Béla; Fóris, Gabriella; Seres, I.; Balogh, Zoltán; Fülöp, Péter; Koncsos, Peter; Paragh, G.

In: Neuropeptides, Vol. 40, No. 5, 10.2006, p. 309-316.

Research output: Contribution to journalArticle

Kosztáczky, Béla ; Fóris, Gabriella ; Seres, I. ; Balogh, Zoltán ; Fülöp, Péter ; Koncsos, Peter ; Paragh, G. / Neuropeptides induced a pronounced and statin-sensitive dysregulation of mevalonate cycle in human monocytes of patients with hypercholesterolemia. In: Neuropeptides. 2006 ; Vol. 40, No. 5. pp. 309-316.
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AU - Seres, I.

AU - Balogh, Zoltán

AU - Fülöp, Péter

AU - Koncsos, Peter

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