The effects of mycophenolate mofetil on cytokines and their receptors in pulmonary arterial hypertension in rats

Scand J Rheumatol. 2015;44(5):412-5. doi: 10.3109/03009742.2015.1023829. Epub 2015 May 11.

Abstract

Objectives: To analyse the effects of mycophenolate mofetil (MMF) on pulmonary artery pressure (PAP) and the expression of cytokines and their receptors in a rat model of pulmonary arterial hypertension (PAH).

Method: Thirty-eight healthy male inbred Sprague-Dawley rats were divided randomly into four groups: a control group, a monocrotaline (MCT) group, an MMF20 group (MCT+20 mg/kg/day MMF), and an MMF40 group (MCT+40 mg/kg/day MMF). Systolic PAP (SPAP), the right ventricular hypertrophy index (RVI), and the levels of expression of cytokines and their receptors were measured and analysed.

Results: SPAP, RVI, levels of expression of basic fibroblast growth factor (bFGF) in serum and lung homogenates, alveolar arterial wall thickness, and the number of muscular arteries in the MMF20 and MMF40 groups were decreased in comparison with the MCT group.

Conclusions: MMF inhibits the formation of vascular muscle and decreases SPAP and RVI by inhibition of the expression of bFGF, endothelin-1 (ET-1), and their receptors, resulting in the inhibition of smooth muscle proliferation and amelioration of PAH.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Cytokines / drug effects*
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Endothelin-1 / drug effects
  • Endothelin-1 / metabolism
  • Fibroblast Growth Factor 2 / drug effects
  • Fibroblast Growth Factor 2 / metabolism
  • Hypertension, Pulmonary / chemically induced
  • Hypertension, Pulmonary / metabolism*
  • Hypertension, Pulmonary / physiopathology
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Monocrotaline / adverse effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A / drug effects
  • Receptor, Endothelin A / metabolism
  • Receptors, Cytokine / drug effects*
  • Receptors, Cytokine / metabolism*
  • Receptors, Fibroblast Growth Factor / drug effects
  • Receptors, Fibroblast Growth Factor / metabolism

Substances

  • Cytokines
  • Endothelin-1
  • Receptor, Endothelin A
  • Receptors, Cytokine
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 2
  • Monocrotaline
  • Mycophenolic Acid