Pressure Load: The Main Factor for Altered Gene Expression in Right Ventricular Hypertrophy in Chronic Hypoxic Rats

PLoS One

Nils E. Magnusson¹  Lars H. Markvardsen¹  Jonas D. Baandrup¹  Ulf Simonsen¹  Jens L. Jensen²  Mogens Kruhøffer³  Torben F. Ørntoft³  Uffe K. Schou⁴  Christian D. Peters⁴ 

[1] Department of Pharmacology, Aarhus University, Aarhus, Denmark;Department of Theoretical Statistics, Institute of Mathematics, Aarhus University, Aarhus, Denmark;Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark;The Water and Salt Research Center, Department of Anatomy, Aarhus University, Aarhus, Denmark

关键词: Cardiac ventricles;    Gene expression;    Medical hypoxia;    Cardiac hypertrophy;    Pulmonary hypertension;    Immunoblotting;    Gene regulation;    Immunohistochemistry techniques;   

DOI  :  10.1371/journal.pone.0015859

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading. Methodology/Principal Findings To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB), sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein) were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase) were downregulated in the PTB and upregulated in the hypoxic experiment. Conclusion/Significance Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure.

【 授权许可】

CC BY