Abstract 13154: Nicotine Decreases Complement Expression, Reduces Fibrosis and Increases Survival in a Zebrafish Model of Heart Failure
Background: The pathology of heart failure (HF) includes several mechanisms including myocardial hypertrophy and disturbance of the renin-angiotensin-aldosterone system. In addition, the occurrence and progression of HF involves two hallmarks: 1) innate immune system activation, including early phase and late phase components and 2) fibrosis. While it has long been established that cigarette smoking is deleterious to our overall health, preliminary studies suggest improved clinical outcomes in cigarette smokers with HF (the "smoker’s paradox"). As molecular mechanisms producing these improvements remain unknown, we hypothesize that nicotine reduces immune system activation, decreases fibrosis and enhances survival rates. In this study, we use the commercial antiseptic oligo-[2-(2-ethoxy)-ethoxyethyl)-guanidinium-chloride](PGH) to induce HF in zebrafish, and determine the effects of nicotine on complement expression levels, fibrosis and survival.
Methods: 24 zebrafish were divided into four treatment groups: 1) control, 2) nicotine (0.1 mg/ml), 3) PGH (10 mM), and 4) PGH pretreated with nicotine (PGH+nic). Time of death was recorded for PGH and PGH+nic groups. Heart tissue was analyzed from all groups by quantitative real-time polymerase chain reaction (qRT-PCR) to determine changes in complement components C6 and C9 expression levels. Histological analysis determined relative fibrosis within cardiac tissue.
Results: qRT-PCR analysis demonstrates that PGH+nic significantly decreases mRNA expression of complement C6 (3.13 fold difference of control with PGH vs 0.1 fold differenced of control with PGH+nic, p < 0.05) and C9 (2.9 fold difference of control with PGH vs 0.03 fold difference of control with PGH+nic, p < 0.05). Histological densitometric analysis demonstrates that PGH+nic animals show significantly reduces fibrosis (2.0 ± 0.1 densitometry units) vs PGH treatment alone (3.6 ± 0.5 densitometry units; p < 0.005). Nicotine improves survival since at t=2 hrs post PGH exposure, 50% of PGH+nic fish were still alive, compared with only 10% of PGH fish.
Conclusions: This study demonstrates nicotine’s ability to lower complement expression, decrease fibrosis in cardiac tissue, and improve survival rates in an HF zebrafish model.
- © 2013 by American Heart Association, Inc.