Signaling cascades in the heart involving caveolae and p38MAP kinases after chronic exposure to Ozone

Increased risk of cardiovascular disease is associated with environmental air pollution exposure. For example, exposure to Ozone (O3), a major component of air pollution, is one of the prime risk factors leading to cardiovascular injury. Earlier studies from this laboratory have shown cardiac dysfunction subsequent to O3 exposure; however specific mechanisms for the O3-induced cardiac dysfunction remain unknown. The current study is a continuation of the previous research work and proposes to: (a) evaluate cardio-pulmonary changes subsequent to various O3 exposure times and; (b) understand the possible intracellular molecular pathways leading to O3 induced cardio toxicity. Twenty age/weight matched male rats were randomly divided into following four groups which were exposed to air (0 ppm ozone) or 0.8 ppm O3 for 8 hours/day for 28 and 56 days: rats exposed to filtered air (FA) for 4 weeks, rats exposed to O 3 for 4 weeks, rats exposed to FA for 8 weeks, rats exposed to O 3 for 8 weeks. Cardiovascular parameters in rats from all groups such as arterial oxygen saturation were measured using a StarrLife Rodent Ox apparatus. These parameters were measured in rats before (0 day) and after (1, 2, 3, 4 and 8 weeks) exposure to air or O3. Our results indicated decreased arterial oxygen saturation levels after O3 exposure (pre-O 3 levels of 98% compared to 93% and 91% after 4 and 8 weeks of O 3 exposure respectively). Upon completion of these measurements, rats were sacrificed, hearts extracted and left ventricular tissue used for various estimations. Western blot analysis was performed to quantify the differences in caveolin-1, caveolin-3 and p38 MAPK alpha levels in air and O3 exposed hearts. Compared to optical density in air exposed group (100 + 5.1 %), caveolin-1 was found to be decreased in 4 week (81 + 6.6 %) and 8 week (40 + 10.6 %) O3 exposed rats. On the other hand differential changes were seen in caveolin-3 levels; i.e. caveolin-3 was increased in the 4 week O3 exposed group (206 + 41 %) and decreased in rats exposed to O3 for 8 weeks (43 + 12.7 %) when compared to air exposed group (100 + 4.5 %). In addition, compared to air exposed group (100 + 6.54 %), p38MAPK alpha was found to be decreased in 4 week (64 + 2.6 %) and 8 week (59 + 6.3 %) O3 exposed rats. This data suggests chronic O 3 exposure depresses physiological cardio-pulmonary parameters and indicates a regulatory role of caveolin-1 and caveolin-3 in O3 induced cardiac toxicity.