Upregulation of myocardial and vascular phosphodiesterase 9A in a model of atherosclerotic cardiovascular disease

Daniel Priksz, Mariann Bombicz, Balazs Varga, Andrea Kurucz, Rudolf Gesztelyi, J. Balla, Attila Toth, Zoltan Papp, Zoltan Szilvassy, Bela Juhasz

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Atherosclerosis is strongly associated with cardiac dysfunction and heart failure. Besides microvascular dysfunction and diminishment of the cardiac nitric oxide-Protein Kinase G (NO-PKG) pathway, recent evidence suggests that phosphodiesterase 9A (PDE9A) enzyme has an unfavorable role in pathological changes. Here, we characterized a rabbit model that shows cardiac dysfunction as a result of an atherogenic diet, and examined the myocardial PDE9A signaling. Rabbits were divided into Control (normal diet) and HC (atherogenic diet) groups. Cardiac function was evaluated by echocardiography. Vascular function was assessed, along with serum biomarkers. Histological stains were conducted, expression of selected proteins and cyclic guanosine monophosphate (cGMP) levels were determined. Signs of diastolic dysfunction were shown in HC animals, along with concentric hypertrophy and interstitial fibrosis. Endothelial function was diminished in HC rabbits, along with marked reduction in the aortic lumen, and increased left ventricle outflow tract (LVOT) pressures. A significant increase was shown in myocardial PDE9A levels in HC animals with unchanged vasodilator-stimulated phosphoprotein (VASP) phosphorylation and cGMP levels. Upregulation of PDE9A may be associated with early stage of cardiac dysfunction in atherosclerotic conditions. Since PDE9A is involved in cGMP degradation and in deactivation of the cardioprotective PKG signaling pathway, it may become an encouraging target for future investigations in atherosclerotic diseases.

Original languageEnglish
Article number2882
JournalInternational journal of molecular sciences
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 2018

Keywords

  • Atherosclerosis
  • Cardiac dysfunction
  • Echocardiography
  • Endothelial dysfunction
  • Phosphodiesterase 9A
  • Rabbit model

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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