Rat models of cardiometabolic diseases: baseline clinical chemistries, and rationale for their use in examining air pollution health effects

Abstract

Individuals with cardiovascular and metabolic diseases (CVD) are shown to be more susceptible to adverse health effects of pollutants. Rodent models of CVD are used for examining susceptibility variations. CVD models developed by selective inbreeding are shown to represent the etiology of human disease and metabolic dysfunction. The goal of this article was to review the origin and the pathobiological features of rat models of varying CVD with or without metabolic syndrome and healthy laboratory rat strains to allow better interpretation of the data regarding their susceptibility to air pollutant exposures. Age-matched healthy Sprague–Dawley (SD), Wistar (WIS) and Wistar Kyoto (WKY), and CVD-prone spontaneously hypertensive (SH), Fawn-Hooded hypertensive (FHH), SH stroke-prone (SHSP), SHHF/Mcc heart failure obese (SHHF) and insulin-resistant JCR:LA-cp obese (JCR) rat models were considered for this study. The genetics and the underlying pathologies differ between these models. Normalized heart weights correlated with underlying cardiac disease while wide differences exist in the number of white blood cells and platelets within healthy strains and those with CVD. High plasma fibrinogen and low angiotensin converting enzyme activity in FHH might relate to kidney disease and associated hypertension. However, other obese strains with known kidney lesions do not exhibit decreases in ACE activity. The increased activated partial thromboplastin time only in SHSP correlates with their hemorrhagic stroke susceptibility. Increases plasma lipid peroxidation in JCR might reflect their susceptibility to acquire atherosclerosis. These underlying pathologies involving CVD and metabolic dysfunction are critical in interpretation of findings related to susceptibility variations of air pollution health effects.

• Air pollution
• cardiovascular disease models
• naturally occurring disease
• rat models
• susceptibility

Acknowledgements

We are grateful to Dr Janice Dye and Dr Gary Hatch (US EPA) for their critical review of this manuscript. The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency and approved for publication. Approval does neither 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.