Long‐Term Exposure of Particulate Matter to Lean and Obese Mice Leads to Cardiac Dysfunction Through Alterations in Beta‐Adrenergic Signaling

Exposure to the particulate matter (PM) component of air pollution causes significant effects on cardiovascular health, specifically exposure to PM less than 2.5 µm in diameter (PM 2.5 ). Numerous studies have linked increases in PM 2.5 levels with cardiovascular events and mortality. In the present study, we exposed adult lean and obese mice to ambient PM 2.5 at relevant concentrations or filtered air (FA) and examined cardiovascular function using echocardiography at regular intervals. At 5 and 9 months, we sacrificed the animals to measure cardiomyocyte contractility and calcium transients, in addition to protein analysis. After 5 months, obese mice exposed to PM 2.5 had reduced fractional shortening (%FS) compared to FA mice, an effect that was not apparent in the lean mice. At 9 months, lean mice had reduced %FS and decreased pulmonary output. Analysis of cardiomyocytes isolated from these mice recapitulated the in vivo phenotype, as cells from the PM 2.5 group had reduced contractile parameters and lengthened calcium reuptake compared to FA exposed mice. PM 2.5 cells treated with isoproterenol (ISO) from both lean and obese groups had an exacerbated contractile response compared with ISO treated cells from the FA groups. Molecular analyses of lean mice exposed for 9 months revealed that PM 2.5 ‐exposed mice had increased phospholamban protein and increased troponin I phosphorylation. We conclude that long‐term exposure to PM 2.5 leads to the reduction of cardiac function by altering contractile proteins, possibly through compensatory alterations to beta‐adrenergic signaling.