Expression of key enzymes in the mevalonate pathway are altered in monocrotaline-induced pulmonary arterial hypertension in rats

Mol Med Rep. 2017 Dec;16(6):9593-9600. doi: 10.3892/mmr.2017.7798. Epub 2017 Oct 17.

Abstract

Pulmonary arterial hypertension (PAH) is a serious pulmonary vascular disease. The changes in the structure, function and metabolism of endothelial cells are some of the important features of PAH. Previous studies have demonstrated that the mevalonate pathway is important in cardiovascular remodeling. However, whether the mevalonate pathway is involved in the development of PAH remains to be elucidated. The present study aimed to investigate the expression pattern of mevalonate pathway-related enzymes in monocrotaline (MCT)-induced PAH. F344 rats were randomly divided into two groups (n=6/group): Control group rats were injected with a single dose of saline, and MCT group rats were injected with a single dose of MCT (60 mg/kg). After 4 weeks, the right ventricular systolic pressure (RVSP) was measured, and lung and pulmonary artery tissue samples were collected. It was demonstrated that the RVSP increased and pulmonary vascular remodeling was detected in the PAH group. The expression levels of the enzymes farnesyldiphosphate synthase farnesyltransferase α and geranylgeranyltransferase type I increased in the PAH group, which suggested that the mevalonate pathway may be involved in the pathological development of PAH.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic*
  • Hemodynamics
  • Hypertension, Pulmonary / chemically induced
  • Hypertension, Pulmonary / genetics*
  • Hypertension, Pulmonary / metabolism*
  • Hypertension, Pulmonary / physiopathology
  • Metabolic Networks and Pathways / genetics*
  • Mevalonic Acid / metabolism*
  • Monocrotaline / adverse effects
  • Nitric Oxide / blood
  • Nitric Oxide Synthase Type III / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • rac1 GTP-Binding Protein / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Reactive Oxygen Species
  • Nitric Oxide
  • Monocrotaline
  • Nitric Oxide Synthase Type III
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein
  • Mevalonic Acid