The pulmonary phenotype during HF is characterized by
vascular remodelling and myeloid cell infiltration
Twelve weeks after MI, mice presented with cardiac dysfunction evidenced
by significantly reduced EF (HF: 37.5% ± 9.4% vs. sham: 63.8% ±
5.9%; Supplemental Table 3 ) and pulmonary structural
alterations confined to the vasculature. HF mice exhibited markedly
thicker blood vessel walls (Fig. 1a, b) and higher smooth
muscle actin (SMA) mRNA (Supplemental Fig. 3 ) and protein
levels (Fig. 1c ) compared to sham-operated controls. HF lungs
did not differ macroscopically nor showed signs of fibrosis demonstrated
by the lack of collagen accumulation assessed by Masson trichrome
staining (Fig. 1d, e ) and hydroxyproline quantification
(Fig. 1f ).
The apparent vascular remodelling was accompanied by higher
monocyte/macrophage association with vascular structures in HF lungs as
illustrated by monocyte/macrophage (MOMA) immunostaining in lung slices
(Fig.2a, b ). Flow cytometric immune cell profiling of the HF
lung revealed significantly higher cell numbers of
CD45hi Ly6C+SiglecF- cells (Fig. 2c, e) and
CD45hi Ly6ChiSiglecF- cells in HF compared to Sham mice
(Fig. 2d, e) , resembling infiltrating macrophages and
pro-inflammatory monocytes. When analysing the activation profile of
F4/80+ macrophages, we observed significantly higher
cell numbers of classically-activated CD80+macrophages in HF lungs (Fig. 2f, i ), indicative of a shift to
a pro-inflammatory phenotype within the macrophage population. This
increase was mainly driven by non-alveolar (SiglecF-)
macrophages (Fig. 2g, i ) as no difference was observed in the
alveolar (SiglecF+) macrophage population
(Fig. 2h, i ).