Second-Hand Smoke–Induced Cardiac Fibrosis Is Related to the Fas Death Receptor Apoptotic Pathway without Mitochondria-Dependent Pathway Involvement in Rats

Abstract

Exposure to environmental tobacco smoke has been epidemiologically linked to heart disease among nonsmokers. However, the molecular mechanism behind the pathogenesis of cardiac disease is unknown. In this study, we found that Wistar rats, exposed to tobacco cigarette smoke at doses of 5, 10, or 15 cigarettes for 30 min twice a day for 1 month, had a dose-dependently reduced heart weight to body weight ratio and enhanced interstitial fibrosis as identified by histopathologic analysis. The mRNA and activity of matrix metalloprotease-2 (MMP-2), representing the progress of cardiac remodeling, were also elevated in the heart. In addition, we used reverse-transcriptase polymerase chain reaction and Western blotting to demonstrate significantly increased levels of the apoptotic effecter caspase-3 in treated animal hearts. Dose-dependently elevated mRNA and protein levels of Fas, and promoted apoptotic initiator caspase-8 (active form), a molecule of a death-receptor–dependent pathway, coupled with unaltered or decreased levels of cytosolic cytochrome c and the apoptotic initiator caspase-9 (active form), molecules of mitochondria-dependent pathways, may be indicative of cardiac apoptosis, which is Fas death-receptor apoptotic-signaling dependent, but not mitochondria pathway dependent in rats exposed to second-hand smoke (SHS). With regard to the regulation of survival pathway, using dot blotting, we found cardiac insulin-like growth factor-1 (IGF-1) and IGF-1 receptor mRNA levels to be significantly increased, indicating that compensative effects of IGF-1 survival signaling could occur. In conclusion, we found that the effects of SHS on cardiomyocyte are mediated by the Fas death-receptor–dependent apoptotic pathway and might be related to the epidemiologic incidence of cardiac disease of SHS-exposed non-smokers.

Exercise training enhanced SIRT1 longevity signaling replaces the IGF1 survival pathway to attenuate aging-induced rat heart apoptosis

“…The apoptotic pathway exhibits increased levels with a reduced survival pathway in these situations. Exercise training and eating purple sweet potato yogurt can help to prevent heart failure and apoptosis Kuo et al 2005;Lin et al 2013;van Tol et al 2006;Huang et al 2012). Spontaneously hypertensive rats (SHR) of advanced age exhibit depressed myocardial contractile function and ventricular fibrosis, and as a result, stable compensatory hypertrophy progresses to heart failure.…”

Effects of Environmental Tobacco Smoke on Adult Rat Brain Biochemistry

“…One such cleaved protein is αII-spectrin, the cleavage product of which is a known marker selective for apoptosis in neurons (Martin et al 1995; Wang et al 1998). ETS chemical extracts induced apoptosis in cardiac cells, with increased Fas and active forms of caspases 3 and 9 (Kuo et al 2005a, b). In contrast, nicotine administration alone was neuroprotective in spinal cord neurons challenged by apoptosis inducing arachidonic-acid.…”

Effects of insulin replacement on cardiac apoptotic and survival pathways in streptozotocin‐induced diabetic rats

“…6,7 Cardiac apoptosis was found in many chronic metabolic and cardiovascular diseases such as obesity, 8,9 diabetes, and hypertension, 7,10 and in various stressful conditions, such as long-term hypoxia, 8,11 or smoke. 12 The occurrence of apoptosis has been often reported to contribute to the loss of cardiomyocytes in myocardial diseases, and is recognized as a predictor of adverse outcomes in patients with cardiac diseases or heart failure. 3 The mitochondrial-dependent apoptotic pathway is activated within cells and is resulted from the release of a number of pro-apoptotic factors from the intermembrane space of mitochondria.…”