Exposure to Diesel Exhaust Particles Drive Expansion of Cardiac Ischemia‐Reperfusion Injury via Interleukin‐6 Trans‐Signaling in Male Sprague‐Dawley Rats

Abstract

Exposure to particulate matter has been strongly associated with deleterious impacts on cardiovascular health and function; however, the mechanisms that underlie this association are largely unknown. We have hypothesized that exposure to particulate matter drives cardiovascular expansion of cardiac ischemia‐reperfusion injury (I/R) via a novel mechanism known as IL‐6 trans‐signaling (IL‐6TS) which promotes a proinflammatory state, increasing susceptibility to inducible injury. To test our hypothesis we exposed male Sprague‐Dawley (SD) rats to an intratracheal (IT) bolus of 200 µg of diesel exhaust particles (DEP) or saline control. To examine inducible injury 24, 48, and 72 hours following IT instillation rats underwent 15 minutes of coronary artery ligation followed by 2 hours of reperfusion. 24 hours after IT exposure to DEP I/R injury was expanded versus control. Likewise, 48 hour following IT instillation I/R injury was elevated versus control, but was reduced from 24 hours. At 72 hours I/R injury was once again elevated to a similar degree as 24 hours. To implicate IL‐6TS in the exacerbation of I/R injury ELISAs for elements of IL‐6TS were performed on serum collected at 24 hours from SD rats exposed to IT DEP; resulting in increases of circulating IL‐6, soluble IL‐6 receptor, and a concomitant decrease in soluble glycoprotein 130, the endogenous antagonist for IL‐6TS. We conclude that exposure to DEP results in a proinflammatory state via IL‐6TS that primes the cardiovascular system for expansion of I/R injury. Funding support in part by Philip Morris International and NIEHS U19 ES019525.