Abstract
BackgroundPathophysiological interactions between heart and lungs in heart failure (HF) are well recognized. We investigated whether expression of different factors known to be increased in the myocardium and/or the circulation in HF is also increased in alveolar macrophages in HF.Methodology/Principal FindingsLung function, hemodynamic parameters, gene expression in alveolar macrophages, and plasma levels in the pulmonary and femoral arteries of HF patients (n = 20) were compared to control subjects (n = 16). Our principal findings were: (1) Lung function was significantly lower in HF patients compared to controls (P<0.05). (2) mRNA levels of ET-1, tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) were increased in alveolar macrophages from HF patients. (3) Plasma levels of ET-1, TNFα, IL-6 and MCP-1 were significantly increased in HF patients, whereas our data indicate a net pulmonary release of MCP-1 into the circulation in HF.Conclusions/SignificanceSeveral important cytokines and ET-1 are induced in alveolar macrophages in human HF. Further studies should clarify whether increased synthesis of these factors affects pulmonary remodeling and, directly or indirectly, adversely affects the failing myocardium.
Highlights
Chronic heart failure (HF) is an important and increasing cause of cardiovascular morbidity and mortality
There was no significant difference in total cell count per mg sputum, there was a trend toward increased cell count in HF patients compared to healthy control subjects
When investigating the correlations between mRNA levels of ET-1 and the cytokines that were up-regulated in alveolar macrophages from HF patients (i.e., TNFa and IL-6) and clinical and hemodynamic parameters in these patients, we found a strong trend toward correlation between IL-6 mRNA levels and left ventricular (LV) function [LV ejection fraction (EF); r = 20.53, p = 0.06]
Summary
Chronic heart failure (HF) is an important and increasing cause of cardiovascular morbidity and mortality. Pathophysiological interactions between the heart and the lungs in HF are well recognized, most attention has been drawn to the effects of impaired left ventricular (LV) filling with increased filling pressure on pulmonary venous circulation [2,3]. Activated alveolar macrophages synthesize numerous vasoactive, mitogenic and inflammatory mediators [4], and these cells are known to be important in various pulmonary disorders like chronic obstructive pulmonary disease (COPD) and sarcoidosis [5,6]. Previous investigations have suggested that recruitment of monocytes from the bloodstream to the lungs and alveoli is facilitated by cytokines, chemokines and vasoactive peptides [4], and several of these mediators are known to be induced in HF [10,11,12]. We investigated whether expression of different factors known to be increased in the myocardium and/or the circulation in HF is increased in alveolar macrophages in HF
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