Ewha Med J.  2018 Jul;41(3):53-62. 10.12771/emj.2018.41.3.53.

Microarray Analysis in Pulmonary Hypertensive Rat Heart after Simvastatin Treatment

• Kim YK
• Kim KC
• Hong YM

• KMID: 2417942
• DOI: http://doi.org/10.12771/emj.2018.41.3.53

Abstract

OBJECTIVES
Simvastatin has been reported to attenuate the development of pulmonary hypertension through increased apoptosis as well as reduced proliferation of smooth muscle cells in obstructive vascular lesions. Microarray experiment can accomplish many genetic tests in parallel. The purpose of this study is to evaluate altered expressions of gene in rat hearts with monocrotaline (MCT)-induced pulmonary arterial hypertension after simvastatin treatment.
METHODS
Six-week-old male rats were grouped as follows: control group (C group, saline injection), M group (MCT 60 mg/kg), and S group (MCT 60 mg/kg plus 10 mg/kg/day simvastatin by gavage during 28 days). Body weight, right ventricular pressure and right ventricular/left ventricle+septum ratio in each group were measured. The rats were sacrificed after 28 days. Total RNA was extracted from the rat heart tissue and microarray analysis was performed.
RESULTS
Administration of simvastatin significantly inhibited the progression of right ventricular hypertrophy at day 28 in the S group than in the M group. Compared with the C group, MCT was associated with a significant difference in expression of genes related to biosynthesis and with the regulation of heart contraction rate. Simvastatin treatment resulted in a significantly changed expression of genes about the regulation of progression through cell cycle and system development compared to the M group. The expressions of nitric oxide synthase and brain natriuretic peptide were significantly decreased after simvastatin treatment.
CONCLUSION
Administration of simvastatin exerted inhibitory effects on right ventricular hypertrophy during the development of MCT-induced pulmonary arterial hypertension in rats. Simvastatin changes the expression of genes associated with various functions.

Keyword

Hypertension, pulmonary arterial; Hydroxymethylglutaryl-CoA reductase inhibitors; Gene expression; Monocrotaline; Simvastatin

MeSH Terms

Animals
Apoptosis
Body Weight
Cell Cycle
Gene Expression
Heart*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypertension
Hypertension, Pulmonary
Hypertrophy, Right Ventricular
Male
Microarray Analysis*
Monocrotaline
Myocytes, Smooth Muscle
Natriuretic Peptide, Brain
Nitric Oxide Synthase
Rats*
RNA
Simvastatin*
Ventricular Pressure
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Monocrotaline
Natriuretic Peptide, Brain
Nitric Oxide Synthase
RNA
Simvastatin

Figure

• 

  Fig. 1 Total gene heat map. C, control; M, monocrotaline; S, simvastatin.

• 

  Fig. 2 Intensity ratio histograph in each group. (A) Monocrotaline vs. control group, (B) simvastatin vs. control group, and (C) simvastatin vs. monocrotaline group.

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