Abstract
BackgroundStrong associations have been observed between exposure to fine ambient particulate matter (PM2.5) and adverse cardiovascular outcomes. In particular, exposure to traffic related PM2.5 has been associated with increases in left ventricular hypertrophy, a strong risk factor for cardiovascular mortality. As much of traffic related PM2.5 is derived from diesel exhaust (DE), we investigated the effects of chronic DE exposure on cardiac hypertrophy and heart failure in the adult mouse by exposing mice to DE combined with either of two mouse models of cardiac hypertrophy: angiotensin II infusion or pressure overload induced by transverse aortic banding.MethodsWild type male C57BL/6 J mice were either infused with angiotensin II (800 ng/kg/min) via osmotic minipump implanted subcutaneously for 1 month, or underwent transverse aortic banding (27 gauge needle 1 week for observing acute reactions, 26 gauge needle 3 months or 6 months for observing chronic reactions). Vehicle (saline) infusion or sham surgery was used as a control. Shortly after surgery, mice were transferred to our exposure facility and randomly assigned to either diesel exhaust (300 or 400 μg/m3) or filtered air exposures. After reaching the end of designated time points, echocardiography was performed to measure heart structure and function. Gravimetric analysis was used to measure the ventricular weight to body weight ratio. We also measured heart rate by telemetry using implanted ambulatory ECG monitors.ResultsBoth angiotensin II and transverse aortic banding promoted cardiac hypertrophy compared to vehicle or sham controls. Transverse aortic banding for six months also promoted heart failure in addition to cardiac hypertrophy. In all cases, DE failed to exacerbate the development of hypertrophy or heart failure when compared to filtered air controls. Prolonged DE exposure also led to a decrease in average heart rate.ConclusionsUp to 6-months of DE exposure had no effect on cardiac hypertrophy and heart function induced by angiotensin II stimulation or pressure overload in adult C57BL/6 J mice. This study highlights the potential importance of particle constituents of ambient PM2.5 to elicit cardiotoxic effects. Further investigations on particle constituents and cardiotoxicity are warranted.
Highlights
Strong associations have been observed between exposure to fine ambient particulate matter (PM2.5) and adverse cardiovascular outcomes
Effects of diesel exhaust exposure combined with angiotensin II infusion To test the effect of DE exposure on cardiac hypertrophy induced by Ang II, we implanted osmotic minipumps for the infusion of Ang II or saline vehicle and exposed mice to either DE or filtered air (FA)
There were increases in left ventricular wall thickness (LV WT) and ventricular weight to body weight ratio (VW/BW) in Ang II infusion groups compared with vehicle groups with both DE and FA exposures (Figure 1A and B), but there were no differences between DE exposed mice and FA controls (Figure 1A and B)
Summary
Strong associations have been observed between exposure to fine ambient particulate matter (PM2.5) and adverse cardiovascular outcomes. PM2.5 is largely derived from diesel exhaust (DE) [10], controlled exposure systems utilizing DE have been routinely used to investigate the cardiovascular effects of PM2.5 inhalation in both humans [11,12,13,14] and animals [15,16,17,18,19,20] These studies have provided evidence that inhalation of DE can increase blood pressure [14], increase left ventricular ischemia [12], decrease vascular nitric oxide bioavailability [18,19], cause vasoconstriction [13], and increase sensitivity to vasoconstricting agents [18]. We hypothesized that acute (1 week) and chronic (1, 3 and 6 months) exposure to DE (300 or 400 μg/m3, 6 hr/day, 5 days/week) would result in an exacerbation of cardiac hypertrophy and failure in mice when exposure occurred simultaneously with angiotensin II (Ang II) infusion or transverse aortic constriction (TAC)
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