In vitro particulate matter exposure causes direct and lung-mediated indirect effects on cardiomyocyte function

Abstract

Particulate matter (PM) exposure induces a pathological response from both the lungs and the cardiovascular system. PM is capable of both manifestation into the lung epithelium and entrance into the bloodstream. Therefore, PM has the capacity for both direct and lung-mediated indirect effects on the heart. In the present studies, we exposed isolated rat cardiomyocytes to ultrafine particulate matter (diesel exhaust particles, DEP) and examined their contractile function and calcium handling ability. In another set of experiments, lung epithelial cells (16HBE14o- or Calu-3) were cultured on permeable supports that allowed access to both the basal (serosal) and apical (mucosal) media; the basal media was used to culture cardiomyocytes to model the indirect, lung-mediated effects of PM on the heart. Both the direct and indirect treatments caused a reduction in contractility as evidenced by reduced percent sarcomere shortening and reduced calcium handling ability measured in field-stimulated cardiomyocytes. Treatment of cardiomyocytes with various anti-oxidants before culture with DEP was able to partially prevent the contractile dysfunction. The basal media from lung epithelial cells treated with PM contained several inflammatory cytokines, and we found that monocyte chemotactic protein-1 was a key trigger for cardiomyocyte dysfunction. These results indicate the presence of both direct and indirect effects of PM on cardiomyocyte function in vitro. Future work will focus on elucidating the mechanisms involved in these separate pathways using in vivo models of air pollution exposure.

Cardiovascular effects of diesel exhaust inhalation: photochemically altered versus freshly emitted in mice

“…Huang et al (Huang et al 2010) demonstrated that acute exposure to DE particles by intra-tracheal instillation produced significant myocardial dysfunction in rats, including decreased left ventricular systolic and diastolic contractility. In addition, exposure to DE particles in vitro resulted in cardiomyocyte contractile dysfunction and reduced calcium handling (Gorr et al 2015). In agreement with these studies, our study found that DE exposure reduced cardiac function and cardiac contractility in isolated perfused hearts.…”

“…The pro-redox components of DE may modulate cardiomyocyte calcium regulation by reducing intracellular calcium or changing sensitivity of contractile proteins to calcium, resulting in diminished cardiac contractility. Gorr et al (Gorr et al 2015) demonstrated that reduced calcium handlings from DE treatment in cardiomyocytes was mediated by cellular oxidative stress. The preserved contractility during reperfusion in hearts exposed to fresh DE could indicate altered intracellular Ca 2+ regulation in the myocardium.…”

Oxygenated polycyclic aromatic hydrocarbons from ambient particulate matter induce electrophysiological instability in cardiomyocytes

“…Indeed, there are some reports that the cardiac effects by DEP, especially arrhythmia, have been attributed to changes in autonomic activity that was not present in cells [41]. However, there are other recent data supporting our results that PM can cross into the pulmonary and systemic circulations directly affecting the heart and blood vessels [42] and DEP has shown both direct and indirect effects on cardiomyocyte functions [43]. The electrophysiological instability by PM or PAHs was completely blocked by pretreatment of the cells with an ROS scavenger, which is consistent with a recent study that revealed that the arrhythmogenic effects induced by DEP were prevented by antioxidant treatment and a CaMKII blockade [9].…”

PM 2.5 exposure in utero contributes to neonatal cardiac dysfunction in mice

“…There is also substantial evidence suggesting a positive correlation between particulate air pollution exposure and adverse cardiovascular outcomes during the postnatal periods 9, 10 . In another study, cardiomyocytes cultured in media from PM-treated lung epithelial cells demonstrated contractile dysfunction 11 . The multitude of PM 2.5 effects (both direct and indirect) on the cardiovascular system are also well reviewed by others 12, 13 These studies are suggestive that PM 2.5 exposure is associated with critical biological and cardio-developmental mechanisms leading to harmful effects later in life.…”