| Abstrakt: |
Smoking, particularly chronic smoking (CS), is a threat to global health, contributing to increased mortality and morbidity associated with cardiovascular disease (CVD). CS induces oxidative stress and endothelial dysfunction, which has a profound impact on cardiac structure and function. While the protective effects of estrogen, particularly 17β-estradiol (E2), on cardiovascular health are well-documented in premenopausal women, the interaction between estrogen and CS remains poorly understood. The aim of this study is to investigate the impact of chronic cigarette smoking on cardiac health in relation to ethinylestradiol (EE) oral contraceptive (OC) usage in premenopausal females. Female mice were exposed to chronic cigarette smoke and co-administered EE. Cardiac structural and functional parameters were assessed alongside inflammatory markers, oxidative stress indicators, and histological changes. Results revealed that the combination of EE and CS led to adverse cardiac remodeling characterized by increased left ventricular end-diastolic volume and elevated left ventricular mass. In addition, an inflammatory state was evident, marked by increased expression of IL-4, IL-1β, IL-13, IL-10, and PARP-1, as well as increased interstitial collagen deposition. These findings suggest a progression towards adverse cardiac remodeling resembling dilated cardiomyopathy. Furthermore, our observations highlight the complexity of the inflammatory response triggered by smoking, potentially exacerbated by estrogen supplementation. The main finding of this study is that the combination of CS and EE enhanced adverse cardiac remodeling, which was shown structurally, histologically, and biochemically. Highlights: To assess the interaction between estrogen supplementation as seen with oral contraceptives and chronic smoking, female mice were exposed to cigarette smoke for 8 weeks and co-administered estrogen. The combination of estrogen and smoking led to adverse cardiac remodeling characterized by increased left ventricular end-diastolic volume and elevated left ventricular mass, suggesting a progression towards remodeling resembling dilated cardiomyopathy. In addition, an inflammatory state was evident, marked by increased expression of IL-4, IL-1β, IL-13, IL-10, and PARP-1, as well as increased interstitial collagen deposition. In contrast, during the 8-week timeframe, smoking by itself did not have structural or functional effects on the hearts of male mice or on female mice, regardless of the presence or absence of endogenous estrogen. Our findings highlight the complexity of the inflammatory response triggered by smoking as exacerbated by estrogen supplementation. Plain language summary: Chronic tobacco smoking contributes to increased mortality and morbidity and is associated with cardiovascular disease. Before menopause, the hearts of women are less affected by smoking due to the protective effects of the hormone estrogen. However, the interaction between estrogen and smoking remains poorly understood in premenopausal females, which was the focus of our study. Such would be the case with smoking woman on oral contraceptives. Female mice were exposed to chronic cigarette smoke for 8 weeks and co-administered estrogen. Heart structure and function were assessed, together with cardiac inflammation, oxidative stress, and histology. Our results revealed that the combination of estrogen and chronic smoking led to adverse cardiac remodeling that was characterized by increased volume of the relaxed left ventricle and elevated left ventricular mass. In addition, an inflammatory state was evident, marked by increased expression of several cytokines and heart fibrosis. These findings suggest a progression towards adverse cardiac remodeling resembling dilated cardiomyopathy. In contrast, during the 8-week timeframe, smoking by itself did not have structural or functional effects on the hearts of male mice or on female mice, regardless of the presence or absence of endogenous estrogen. Thus, our findings highlight the complexity of the inflammatory response triggered by smoking as exacerbated by estrogen supplementation. Further preclinical animal and clinical studies are needed to define the mechanisms behind these adverse effects. [ABSTRACT FROM AUTHOR] |
