Mitigation of PM2.5 Induced cardiovascular damage by statins and ACE inhibitors

K. Marin (Mainz)¹, T. Junglas (Mainz)¹, I. Kuntic (Mainz)¹, M. Oelze (Mainz)¹, L. Strohm (Mainz)¹, H. Ubbens (Mainz)¹, J. Zheng (Mainz)¹, A. Valar (Mainz)¹, M. T. Bayo Jimenez (Mainz)¹, O. Hahad (Mainz)², T. Münzel (Mainz)³, A. Daiber (Mainz)^1
1Universitätsmedizin der Johannes Gutenberg-Universität Mainz Labor für Molekulare Kardiologie Mainz, Deutschland; ²Universitätsmedizin der Johannes Gutenberg-Universität Mainz Zentrum für Kardiologie, Kardiologie I Mainz, Deutschland; ³Universitätsmedizin der Johannes Gutenberg-Universität Mainz Kardiologie 1, Zentrum für Kardiologie Mainz, Deutschland

Particulate matter (PM) is well recognized as the major contributor to the air pollution disease burden. Presently, the data pointing to the direct effects of PM on the cardiovascular health are numerous, but the mitigation strategies are still at the level of reduction of exposure. This is of specific importance since it may be assumed that patients with pre-established chronic diseases, e.g. ischemic heart disease, are at particular risk of exacerbated PM-mediated damage. In the present study we used a mouse model of real-life PM_2.5 exposure treated with either a statin (atorvastatin) or an ACE inhibitor (captopril) in order to observe the potentially protective effects of cardiovascular drug treatment on the underlying mechanisms of detrimental, PM_2.5-induced, cardiovascular effects. Captopril treatment mitigated the PM_2.5-induced blood pressure while both drugs reduced vascular endothelial dysfunction. Both drugs were successful in mitigating the vascular oxidative stress by reducing the expression of the NADPH oxidase enzyme. The atorvastatin treatment also reduced the level of 3-NT positive proteins by trend and mitigated the effects on dysregulated eNOS expression. Either drug did not mitigate the inflammatory response in the lung and in circulation with only captopril reducing the pulmonary IL-6, but not CD68 expression. Similar lack of effect was observed for inflammatory signaling in the heart tissue pointing to the inability of either drug to mitigate the PM_2.5-induced systemic inflammation. In summary, ACE inhibitors can potentially mitigate the detrimental effects of PM_2.5 on vascular function and oxidative stress through lowering of blood pressure and statins have a known antioxidant effect, e.g. via inhibition of NADPH oxidase. Our present data provide novel insights into possible mitigation strategies for PM_2.5-induced cardiovascular disease. Since statins and ACE inhibitors represent first-line therapies for cardiovascular disease, CVD patients, e.g. with coronary artery disease, ischemic heart disease and hypertension, may benefit from standard therapies with these drugs to prevent additive cardiovascular damage by PM_2.5 exposure. Protection of these highly vulnerable groups against air pollution mediated health effects is a priority topic of the actual EU agenda and many clinical guidelines.