Upregulation of Myocardial and Vascular Phosphodiesterase 9A in A Model of Atherosclerotic Cardiovascular Disease.
Daniel PrikszMariann BombiczBalazs VargaAndrea KuruczRudolf GesztelyiJózsef BallaAttila TóthZoltan PappZoltan SzilvassyBela JuhaszPublished in: International journal of molecular sciences (2018)
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.
Keyphrases
- left ventricular
- nitric oxide
- protein kinase
- heart failure
- cardiovascular disease
- signaling pathway
- oxidative stress
- early stage
- cardiac resynchronization therapy
- mitral valve
- poor prognosis
- physical activity
- weight loss
- cell proliferation
- squamous cell carcinoma
- pulmonary hypertension
- aortic valve
- type diabetes
- long non coding rna
- epithelial mesenchymal transition
- radiation therapy
- pi k akt
- induced apoptosis
- metabolic syndrome
- current status
- binding protein
- sentinel lymph node
- endoplasmic reticulum stress