Fig. 3: Heart microvascular dysfunction and fibrosis in Hutchinson-Gilford progeria syndrome (HGPS) minipigs.

a Left ventricular (LV) fibrosis in HGPS minipigs revealed by delayed gadolinium enhancement magnetic resonance imaging (MRI). Representative images are shown. Red arrowheads indicate the area of contrast deposition. b LV microvascular damage in HGPS minipigs determined by cardiac MRI-determined absolute quantitative perfusion after gadolinium administration (n = 6 WT and n = 7 HGPS minipigs, 4.3–5.5 months old). The images show representative examples of LV flow with perfusion ranging from 50 (red) to 200 (yellow) ml/min/100 g. Arrowheads indicate the non-perfused area. c Collagen deposition in LV and septal coronary arteries of WT and HGPS hearts. Images show representative Masson trichrome (MT) staining of heart cross sections, revealing increased collagen deposition (green/blue staining) in HGPS hearts. Left and center graphs: mean percentage collagen content in medial and adventitial layers of arterioles >65 μm in diameter, quantified by image deconvolution (area analyzed, 170 mm² in LV and 120 mm² in septum). Right graph: adventitial hyperthrophy quantified as the ratio of adventitial to medial perimeter (11–27 arterioles of mean diameter >50 μm per minipig in LV or septum). d Smooth muscle cell loss in the medial layer of LV and septum arterioles in HGPS minipigs. Representative immunofluorescence images show staining for α-smooth muscle actin (SMA) in red, CD31 (endothelial cell marker) in green, and nuclei in blue. The graph shows mean percentage SMA signals in the medial layer of 12–41 arterioles per minipig in LV or septum. See also Supplementary Fig. S4. e Representative images of MT staining in heart cross sections, showing myocardial fibrosis in HGPS minipigs. Black arrows indicate areas of intense MT staining. Images were deconvoluted to quantify mean percentage myocardial fibrosis in vessel-free myocardial areas (seven areas in LV and six areas in septum; 470 μm² each region analyzed)