Abstract
The strong relationship between cigarette smoking and cardiovascular disease (CVD) has been well-documented, but the mechanisms by which smoking increases CVD risk appear to be multifactorial and incompletely understood. Mesenchymal stem cells (MSCs) are regarded as an important candidate for cell-based therapy in CVD. We hypothesized that MSCs derived from induced pluripotent stem cell (iPSC-MSCs) or bone marrow (BM-MSCs) might alleviate cigarette smoke (CS)-induced cardiac injury. This study aimed to investigate the effects of BM-MSCs or iPSC-MSCs on CS-induced changes in serum and cardiac lipid profiles, oxidative stress and inflammation as well as cardiac function in a rat model of passive smoking. Male Sprague-Dawley rats were randomly selected for exposure to either sham air (SA) as control or 4% CS for 1 h per day for 56 days. On day 29 and 43, human adult BM-MSCs, iPSC-MSCs or PBS were administered intravenously to CS-exposed rats. Results from echocardiography, serum and cardiac lipid profiles, cardiac antioxidant capacity, cardiac pro- and anti-inflammatory cytokines and cardiac morphological changes were evaluated at the end of treatment. iPSC-MSC-treated group showed a greater effect in the improvement of CS-induced cardiac dysfunction over BM-MSCs-treated group as shown by increased percentage left ventricular ejection fraction and percentage fractional shortening, in line with the greater reversal of cardiac lipid abnormality. In addition, iPSC-MSCs administration attenuated CS-induced elevation of cardiac pro-inflammatory cytokines as well as restoration of anti-inflammatory cytokines and anti-oxidative markers, leading to ameliorate cardiac morphological abnormalities. These data suggest that iPSC-MSCs on one hand may restore CS-induced cardiac lipid abnormality and on the other hand may attenuate cardiac oxidative stress and inflammation via inhibition of CS-induced NF-κB activation, leading to improvement of cardiac remodeling and dysfunction. Thus, iPSC-MSCs may be a promising candidate in cell-based therapy to prevent cardiac complications in smokers.
Highlights
Cigarette smoking, one of the major risk factors for the development of cardiovascular disease (CVD), accounts for morbidity and mortality of cardiac events, including coronary heart disease, atherosclerosis, myocardial infarction and stroke (Burns, 2003)
The cigarette smoke (CS)-exposed rats (CS group) developed cardiac contractile dysfunction that was characterized by significantly iPSC-Mesenchymal stem cells (MSCs) Attenuate Smoking-Induced Cardiac Dysfunction decreased %LVEF and %FS when compared with sham air (SA)-exposed rats (SA group) (p < 0.01, respectively), which was significantly restored to a normal status in the presence of iPSC-MSCs but not BM-MSCs
Serum free fatty acids (FFA) level showed a trend of elevation in the CS group compared to the SA group but not reaching significant level, which was not reversed in the presence of either BM-MSCs or iPSC-MSCs
Summary
One of the major risk factors for the development of cardiovascular disease (CVD), accounts for morbidity and mortality of cardiac events, including coronary heart disease, atherosclerosis, myocardial infarction and stroke (Burns, 2003). The association between CVD and the effect of passive (secondhand) smoking needs to be taken into consideration, as passive smoking increases the risk of coronary heart disease, myocardial infarction, stroke and cardiac death (Barnoya and Glantz, 2005; Minicucci et al, 2009). Fatty acids are utilized by the heart to generate a constant supply of ATP needed for normal myocardial function (Stanley et al, 2005). Cardiac lipid profile affects electrophysiological and mechanical function due to modulation of the physicochemical properties of cellular membranes (van der Vusse et al, 2000). The physiological and biochemical responses to CS have not been fully characterized in terms of cardiac lipid profile and function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
