Cardiac and pulmonary expression of renin, prorenin, mast cells and macrophages in a rat model of fat embolism syndrome

Abstract

Fat embolism induced in rats by intravenous injection of triolein(T) causes pulmonary inflammation, fibrosis, and vasculitis after 48 hours ort 10 weeks. Administration of Aliskiren, Captopril and Losartan drugs, which interfere with the renin angiotensin aldosterone system, ameliorates the pulmonary damage. Macrophages and mast cell number decreased with drugs administration. Hearts do not exhibit inflammation or vasculitis although significant emboli are detected at 48 hours. Pulmonary expression of renin, prorenin(R/P) positive cells are also increased after T injection. This study investigates whether the presence of R/P cells correlates with macrophages and mast cell invasion in the hearts and lungs.Methodology24 Sprague Dawley rats were divided into four groups and treated with 0.2 ml of T or Saline. Lungs and hearts from 3 animals from each group that were sacrificed 48 hours or 10 weeks, fixed in formalin and stained with Hematoxylin‐Eosin, Trichrome or immunostained with antibodies to CD117, CD68 to identify mast cells and macrophages. Sections of the heart and the lung were evaluated at 400X magnification. Cells were counted, histopathology examined and statistical significance evaluated using GraphPad software.ResultsWhile the lungs showed the previously reported, histopathological damage caused by the inflammation, vasculitis, fibrosis and cell necrosis, the hearts did not show such damage, thus confirming previous observations.Contrary to the lungs where the number of CD117, CD68 and R/P positive cells was significantly increased at both interval times, no difference in CD117, CD68, R/P positive cell numbers were observed in the heart. In the lungs, two distinct types of macrophages were identified, one large and the second one of normal size. Such histopathological changes were not observed in the hearts. Hearts exhibited distinct locations of CD117 and CD68 positive cells, with multiple cells located primarily near the myocardium and few in the adventitia of the coronary arteries, in contrast to lungs where the cells were mostly located around the arteries.ConclusionThe study confirms the previously reported histopathological difference of the T induced damage in the lungs compared to that of the hearts in this model of fat embolization. This finding highlights the variation in cellular response of diverse organs to fat embolism. This difference is not only related to the number of the inflammatory cells but also to their location in different organs as evidenced by the difference in the distribution and location of R/P cells in hearts and lungs. Future studies will investigate the underlying mechanisms that lead to pulmonary susceptibility while preserving cardiac integrity in response to a FE induced inflammatory response in order to better design a therapeutic intervention for the fat embolism syndrome.