Left ventricular gene expression profile of healthy and cardiovascular compromised rat models used in air pollution studies

Abstract

The link between pollutant exposure and cardiovascular disease (CVD) has prompted mechanistic research with animal models of CVD. We hypothesized that the cardiac gene expression patterns of healthy and genetically compromised, CVD-prone rat models, with or without metabolic impairment, will reveal underlying disease processes that facilitate understanding of the mechanisms of air pollution susceptibility differences. Left ventricular gene expression was examined using Affymetrix rat 230A-gene arrays in male, age-matched (12–14 weeks old) healthy Wistar Kyoto (WKY) and CV-compromised spontaneously hypertensive (SH), stroke-prone SH (SHSP), obese SH heart failure (SHHF) and obese insulin-resistant (JCR) rats. Principle component analysis separated strains in three clusters: (1) WKY, (2) JCR and (3) SH, SHSP and SHHF. Gene expression pattern in JCR differed from all other CVD strains. Both SHHF and JCR strains presented the most differentially expressed genes from WKY, but generally with opposing directional pattern suggesting that the CVD in these strains arise through different mechanisms. Hierarchical clustering of nuclear factor-kappaB target genes indicated varying degrees of, but similar directional changes, in SH, SHSP and SHHF relative to WKY rats, which may relate to the severity of their CVD. The JCR strain had less pronounced expressions of these genes suggesting milder cardiac disease. No unique expression pattern could be identified for genes implicated in stroke and heart failure in SHSP and SHHF rats, respectively. The data show that the CVD pathophysiological mechanisms differ in models with different genetic backgrounds, and therefore, the mechanisms by which air pollutants affect the cardiopulmonary system are likely to vary.

• Cardiac expression profiling
• cardiovascular disease models
• metabolic syndrome

Acknowledgements

We are grateful to Drs. Daniel L. Costa, Barbara Buckley and Martha Sue Carraway of the US EPA and Dr. Alex Carll of the University of North Carolina (Chapel Hill, NC) for their critical review of this manuscript.

Declaration of interest

The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and the policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Supplementary material available online

Supplementary Tables 1-4.