Fig. 6: Conditional ITGA5 deletion in CX3CR1+ macrophages accentuates dilative post-infarction remodeling, perturbing infarct angiogenesis and vascular maturation.

Echocardiographic assessment showed that inducible macrophage–specific ITGA5 knockout mice (iMaα5KO) had accentuated dilative remodeling after myocardial infarction, evidenced by increased left ventricular end-diastolic volume (LVEDV; A) and left ventricular end-systolic volume (LVESV; B) after 28 days of coronary occlusion. C The effects of macrophage-specific ITGA5 loss on left ventricular ejection fraction (LVEF; C) did not reach statistical significance (***p < 0.001, ITGA5 fl/fl pre: n = 14, iMaα5KO pre: n = 14, ITGA5 fl/fl 7d: n = 5, iMaα5KO 7d: n = 4, ITGA5 fl/fl 28d: n = 9, iMaα5KO 28d: n = 9 biologically independent experiments). D Representative images show CD31 immunohistochemical staining of infarcted area, border zone, and remote remodeling myocardium in ITGA5 fl/fl and iMaα5KO mice after 7 and 28 days of coronary occlusion. The arrow identifies a typical microvessel. iMaα5KO mice had significantly reduced microvascular density in the infarct zone (E) and in the border zone (F) after 28 days of coronary occlusion. Microvascular density in the remote remodeling myocardium was comparable between iMaα5KO mice and corresponding ITGA5 fl/fl controls (G). H In healing infarcts, microvessels undergo maturation acquiring a coat comprised of α-SMA-expressing mural cells (arrowheads). Representative images of α-SMA immunofluorescence staining from infarcted area and remote area of ITGA5 fl/fl and iMaα5KO mice after 7 and 28 days of coronary occlusions are shown. The arrow identifies a typical α-SMA+ microvessel. iMaα5KO mice had significantly reduced density of mature α-SMA+ microvessels in the infarct zone at the 28-day timepoint (I). The density of α-SMA+ vessels in the remote remodeling myocardium was comparable between groups (J) (****p < 0.0001, *p < 0.05, ITGA5 fl/fl 7d: n = 5, iMaα5KO 7d: n = 5, ITGA5 fl/fl 28d: n = 9, iMaα5KO 28d: n = 9 biologically independent experiments). Statistical analysis was performed using one-way ANOVA followed by post-hoc Sidak tests. Data are shown as mean values +/- SEM. Source data are provided as a Source Data file. Scale bar = 100um. I infarct area, R remote area.