an on Mast Cells in the Hearts of Rats 10 Weeks after Fat Embolism with Triolein
Authors: Fletcher Amanda N , Poisner Alan M , Hamidpour Soheila , Patel Chirag , Pamulapati Hema , Ponnapureddy Rakesh , Greenberg Ian , Simon Steve , Molteni Agostino 
Published: November 2023

In a rat model of fat embolism (FE) induced by i.v. triolein (T), severe lung damage develops up to 10 weeks post treatment1. The damage which is reduced by concomitant administration of the angiotensin II type 1 receptor blocker losartan (Los)2 was associated with an elevated level of renin in the lungs.3 Reports indicate that mast cells (MCs) are associated with the renin increase observed in the lungs.4 FE damage, however, is not limited to the lungs. Hearts of the same rats had severe inflammation of the coronary arteries with medial thickening, reduced lumen patency, adventitial fibrosis, and myocardial inflammation, which was also blocked by Los.5 We have now extended our investigation of the heart to the potential role of mast cells (MCs) in the pathogenesis of cardiovascular damage.

Twenty‐two Sprague Dawley rats (~300 gm BW) received either T (0.2 mL i.v.) or saline. Six weeks later, half of the rats of each subgroup were given Los or saline). Four weeks later (10 weeks post T injection), rats were euthanized with isoflurane, and necropsied. Hearts were fixed in 10% formalin and stained with H&E (morphometric scoring), trichrome (fibrosis) and CD 11‐c kit (MCs). On each heart slide 10 photographs were taken at random at 400× and MCs counted by two pathologists unaware of the slide identity.

Severe vasculitis, perivascular fibrosis, and myocardial inflammation were present in the hearts of T treated rats vs saline controls. Los markedly reduced this damage, but had no effect on MCs in the presence of absence of T. MC number. T caused a non‐significant increase in MCs number compared to saline controls (20.7 +/− 5.3 vs 13.1 +/− 5.1: mean +/− STdev). The results suggest that, although MCs are present in hearts of rats 10 weeks after T where vascular inflammation and histopathological damage is similar to that observed in the lungs, their number is more modestly increased and not affected by Los treatment.

The trend of an increase in MCs in the heart 10 weeks after T suggests a potential role of MCs in the pathogenesis of cardiovascular damage. Despite the severe inflammatory and vascular response and the protective effect of Los from perivascular fibrosis, the role of MCs in the heart at this late time after T may suggest different pathways or time course for histopathological changes compared to the lungs. It remains to be seen if the appearance of MCs in the heart after T is greater at earlier time points when the lung pathology is also greater.

Support or Funding Information

Mary Katherine Geldmacher Research Foundation, St. Louis, MO; This work was supported by a CTSA grant from NCRR and NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research # TL1TR000120. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NCRR, or NCATS.