Resveratrol Protects Against Functional Impairment and Cardiac Structural Protein Degradation Induced by Secondhand Smoke Exposure

• Published in: Canadian journal of cardiology 2013-10, Vol.29 (10), p.1320-1328
• Main Authors: Arcand, Steven, Sharma, Keshav, Al-Dissi, Ahmad N., DVM, PhD, Cadete, Virgilio J.J., PhD, Sawicki, Grzegorz, PhD, Weber, Lynn P., PhD
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Cardiovascular; Disease Models, Animal; Male; Myocardium - metabolism; Myocardium - pathology; Oxidative Stress - drug effects; Proteins - drug effects; Proteins - metabolism; Proteolysis; Proteomics - methods; Recovery of Function; Stilbenes - pharmacology; Swine; Tobacco Smoke Pollution - adverse effects; Vasodilator Agents; Ventricular Dysfunction - drug therapy; Ventricular Dysfunction - metabolism; Ventricular Dysfunction - physiopathology; Ventricular Function - drug effects; Ventricular Function - physiology
• ISSN: 0828-282X; 1916-7075
• DOI: 10.1016/j.cjca.2013.04.030

Abstract Background Secondhand smoke (SHS) impairs cardiac function and resveratrol is cardioprotective, possibly via antioxidant and anti-inflammatory capabilities. Previously, it was shown that resveratrol protects against SHS-induced cardiac dysfunction, but the molecular mechanism is not clear. Methods We measured cardiac function in pigs exposed to SHS alone in a first experiment or with and without resveratrol (5 mg/kg/day) in a second experiment using echocardiography and compared this with proteomic changes. Results In the first experiment after 28 days, end-diastolic volume, end-systolic volume, and stroke volume were all impaired in SHS pigs compared with control pigs, with cardiac output significantly depressed as early as 14 days. Depressed function corresponded to increased inflammation, oxidative stress, and matrix metalloproteinase-2, but decreased intact myosin light chain 1 in SHS compared with control pigs at 28 days. In our second study after 14 days, two-dimensional electrophoresis detected 6 significantly increased protein spots in SHS compared with control pigs. Mass spectrometry identified 4 spots as fragments of sarcomeric protein (1 myosin light chain 1, 1 β-myosin heavy chain, and 2 myosin-7), and 2 spots as glucose metabolism enzymes (lactate and pyruvate dehydrogenases). Resveratrol normalized the fragmented protein levels, but not the metabolic enzymes. At 14 days, matrix metalloproteinase-2 activity almost doubled in cardiac tissue from SHS compared with control pigs, and resveratrol appeared to normalize it. Conclusions Thus, the ventricular differences in protein expression might explain the mechanism by which SHS reduces critical hemodynamic parameters through the degradation of sarcomeres, appearing to be prevented by resveratrol administration.