AUTHOR=Alavi Samaneh Sadat , Joukar Siyavash , Rostamzadeh Farzaneh , Najafipour Hamid , Darvishzadeh-mahani Fatemeh , Mortezaeizade Abbas TITLE=Involvement of Sirtuins and Klotho in Cardioprotective Effects of Exercise Training Against Waterpipe Tobacco Smoking-Induced Heart Dysfunction JOURNAL=Frontiers in Physiology VOLUME=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.680005 DOI=10.3389/fphys.2021.680005 ISSN=1664-042X ABSTRACT=Despite its negative effect on cardiovascular system, nowadays waterpipe smoking (WPS) is popular worldwide, especially among youth. This study investigated the effects of moderate endurance exercise on heart function of rats exposed to WPS and its possible mechanism. The animals were randomly divided into 4 groups as: control group (CTL), the exercise group (Ex) which trained for 8 weeks, the waterpipe tobacco smoking group (S) exposed to smoking (30 minutes per day, 5 days each week, for 8 weeks), and the group that did exercise training and received waterpipe tobacco smoking together (Ex+S). One day after last session of Ex and WPS, the cardiac pressures and functional indices were recorded and calculated. The levels of SIRT1, SIRT3, Klotho, Bax and Bcl-2 in the serum and heart, the expression of phosphorylated GSK3β of heart tissue and the cardiac histopathological changes were assessed. WPS increased the cardiac tissue lesions (P<0.05 vs. CTL), reduced systolic pressure, +dP/dt max, -dp/dt max, and heart contractility indices (P < 0.001 vs. CTL) and increased the end diastolic pressure and Tau index (P < 0.001 vs. CTL) of the left ventricle. Exercise training normalized the left ventricular end diastolic pressure, +dp/dt max and contractility index. Also, exercise improved the levels of SIRT1, SIRT3, Klotho and Bcl-2 and reduced the Bax level in heart. The findings showed that WPS causes left ventricular dysfunction. Moderate exercise prevented WPS-induced heart dysfunction partly through its anti- apoptotic features and activating of the sirtuins and klotho pathways.