Fig. 3: SWNTs accumulate in atherosclerotic plaque and SHP1 inhibition reduces both vascular inflammation and apoptotic cell accumulation in transgenic atherosclerotic pigs, in vivo. | Nature Communications

Fig. 3: SWNTs accumulate in atherosclerotic plaque and SHP1 inhibition reduces both vascular inflammation and apoptotic cell accumulation in transgenic atherosclerotic pigs, in vivo.

From: Pro-efferocytic nanotherapies reduce vascular inflammation without inducing anemia in a large animal model of atherosclerosis

Fig. 3

a Experimental workflow including downstream analyses. b Bar diagram of SWNT uptake in monocytes/macrophages versus non-monocytes/macrophages in multiple vascular beds of the pooled SWNT and SWNT-SHP1i treated pigs. MO stands for monocytes and MΦ stands for macrophages. SWNT/SWNT-SHP1i uptake by MO/MΦ was significantly higher than non-MO/MΦ in vascular beds including the carotid artery (***p = 0.0001), iliac artery (**p = 0.0066), and renal artery bifurcation (**p = 0.0049) as analyzed by an unpaired two-tailed t-test with Welch’s correction. No significant difference was observed in SWNT/SWNT-SHP1i uptake by MO/MΦ compared to non-MO/MΦ in non-vascular tissue such as the bone marrow (p = 0.6314). Data are presented as mean values ± SEM. Carotid artery n = 2 (SWNT), n = 2 (SWNT-SHP1i); iliac artery n = 2 (SWNT), n = 3 (SWNT-SHP1i); renal artery bifurcation n = 2 (SWNT), n = 3 (SWNT-SHP1i); bone marrow n = 2 (SWNT), n = 3 (SWNT-SHP1i) over biologically independent samples. c Pigs treated with SWNT-SHP1i had similar atherosclerotic lesion sizes as SWNT controls in the RCA ostium (p = 0.5763). Data are presented as mean values ± SEM. n = 6 (SWNT) and n = 5 (SWNT-SHP1i) over 11 independent biological samples. d 18F-FDG PET/CT imaging and analysis of the carotid arteries demonstrate that SWNT-SHP1i significantly reduces vascular inflammation. *p = 0.0438 by an unpaired two-tailed t-test with Welch’s correction. Data are presented as mean values ± SEM. n = 5 (SWNT) and n = 5 (SWNT-SHP1i) over 10 independent biological samples. e In SWNT-SHP1i treated pigs, macrophage infiltration into the atherosclerotic lesion was not significantly lower than in SWNT controls (p = 0.4339). Data are presented as mean values ± SEM. n = 6 (SWNT) and n = 5 (SWNT-SHP1i) over 11 independent biological samples. f The RCA ostium of SWNT-SHP1i treated pigs contained significantly fewer TUNEL-positive apoptotic bodies compared to SWNT controls. *p = 0.0280 by unpaired two-tailed t-test with Welch’s correction. Data are presented as mean values ± SEM. n = 6 (SWNT) and n = 5 (SWNT-SHP1i) over 11 independent biological samples. Source data are provided as a Source data file. Figure 3/panel a created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license (https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en).

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