Premium
Smoking‐Induced Changes in Myocardial Pigment Epithelium‐Derived Factor: Implications for Cardiovascular Disease
Author(s) -
McHowat Jane,
Adney Jacob,
Kennedy Kelsey R.,
Kispert Shan E.,
Roberts Jacob,
Hui Dawn S.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04670
Subject(s) - medicine , diabetes mellitus , myocardial infarction , risk factor , cardiology , coronary artery disease , disease , incidence (geometry) , heart failure , gastroenterology , endocrinology , physics , optics
Cigarette smoking remains a significant contributor to cardiovascular disease, resulting in approximately 6 million deaths per year worldwide. Despite the well‐established correlation between smoking and coronary artery disease, very few studies have examined direct changes in the myocardium in the presence of smoking. We propose that smoking is associated with platelet‐activating factor (PAF) accumulation, an inflammatory metabolite that is implicated in ischemia/reperfusion injury and heart failure progression. PAF has been shown to enhance matrix metalloproteinase (MMP) activation, which may contribute to downregulation of pigment epithelium‐derived factor (PEDF), a glycoprotein with anti‐inflammatory and antioxidative properties that can protect against impaired cardiac function, tissue remodeling, endothelial damage, platelet aggregation and T–cell activation. We collected atrial tissue from 157 patients scheduled for cardiothoracic surgery at Saint Louis University Hospital. Patient smoking history, past medical history, and surgical and post‐operative data was collected. Patients were grouped as never smokers, second hand smoke exposure, current smokers and previous smokers (further stratified according to time since last cigarette, <1, 1–10 and >10 years). All groups were similar for age, race, gender, BMI, incidence of diabetes and hypertension, and the number of coronary vessels diseased/bypassed. There was a significantly higher incidence of prior myocardial infarction and diagnosis of chronic obstructive airways disease in smokers when compared to never smokers. However, glomerular filtration rate was lower in never smokers when compared to smokers. These differences remained between previous smokers and never smokers, regardless of length of smoking cessation. Biochemical analysis was performed in atrial tissue removed from human heart during cardiac surgery for 18 samples from smoker and never smoker groups (coronary artery bypass grafting, n=35; aortic valve surgery, n=1). There was no significant difference between the two groups for age, sex, number of diseased vessels, number of vessels bypassed, left ventricular ejection fraction or days of inotropy post‐op. We observed a significant increase in PAF accumulation in the myocardium obtained from smokers (4.29 ± 0.37 compared to 3.19 ± 0.28 ng/mg protein, p<0.05). Immunoblot analysis for the PAF‐receptor showed no change in myocardial expression between smokers and never smokers. Immunoblot analysis of PEDF content normalized to GAPDH in the human myocardium was reduced in smokers when compared to never smokers (1.04 ± 0.06 to 0.75 ± 0.07, p<0.01), but no difference MMP expression was detected. These are the first data to implicate PEDF downregulation in smoking‐related cardiovascular disease and supports previous evidence of the cardioprotective benefits of PEDF. Future studies will analyze whether increased PAF accumulation or decreased PEDF expression in smoker myocardium contribute to compromised cardiac function following myocardial ischemic events, including the demands of cardiac surgery.