Elevation of hemopexin-like fragment of matrix metalloproteinase-2 tissue levels inhibits ischemic wound healing and angiogenesis April E. Nedeau, MD,

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Presentation transcript:

Elevation of hemopexin-like fragment of matrix metalloproteinase-2 tissue levels inhibits ischemic wound healing and angiogenesis April E. Nedeau, MD, Katherine A. Gallagher, MD, Zhao-Jun Liu, MD, Omaida C. Velazquez, MD Journal of Vascular Surgery Volume 54, Issue 5, Pages 1430-1438 (November 2011) DOI: 10.1016/j.jvs.2011.05.029 Copyright © 2011 Society for Vascular Surgery Terms and Conditions

Fig 1 A, Concentration of peroxisomal biogenesis factor 2 (PEX2), calculated by pixel density in gastrocnemius muscle, is shown as a fold-increase vs control when observed by Western blot. Fold-increase calculations were standardized with glyceraldehyde-3-dehydrogenase (GAPDH) loading control. PEX2 is elevated 6.6-, 2.6-, 16-, and 5.3-fold vs control on postoperative days (POD) 2, 4, 6, and 8, respectively. The range bars show the standard error of the mean. B, Representative Western blot shows gastrocnemius muscle after femoral artery ligation at various time points, when probed with antimatrix metalloproteinase (MMP)-2 and anti-GAPDH antibodies. C, Representative laser Doppler imaging shows murine hind limbs at various intervals before gastrocnemius muscle harvest. Perfusion is indicated by color: red hind limbs have the greatest level of perfusion, yellow and green, show a gradient of blood flow, and blue hind limbs are ischemic. Journal of Vascular Surgery 2011 54, 1430-1438DOI: (10.1016/j.jvs.2011.05.029) Copyright © 2011 Society for Vascular Surgery Terms and Conditions

Fig 2 A, Graph shows average percentage decrease in the surface area of muscle exposed to human recombinant peroxisomal biogenesis 2 (hrPEX2) factor at various intervals. Control wounds were covered with granulation tissue by postoperative day (POD) 3, whereas muscle continued to be exposed on wounds injected with hrPEX2 by POD 7. The percentage decrease in the exposed muscle of hrPEX2 wounds was reduced by 12% to 16% over PODs 1 to 5 and by 6.0% over POD 6 and 7 (P < .02). The error bars show the standard error of the mean. B, Representative photographs show wounds at various intervals after wound induction. The entire wound reveals exposed muscle in both groups on the operation day (OD). Photographs taken on POD 3, 5, and 7 demonstrate decreasing surface area of exposed muscle. Journal of Vascular Surgery 2011 54, 1430-1438DOI: (10.1016/j.jvs.2011.05.029) Copyright © 2011 Society for Vascular Surgery Terms and Conditions

Fig 3 A, Graph shows a comparison of the epithelial gap, or the distance between epithelial edges in micrometers, between wounds in mice injected with lentivirus expressing peroxisomal biogenesis 2 (PEX2-LV) and control mice injected with lentivirus expressing green fluorescent protein (GFP-LV). The average distance was 1.6 ± 0.3 μm for wounds expressing PEX2 vs 0.64 ± 0.31 μm for controls (P < .05). The error bars show the standard error of the mean. B, Representative sections show wounds on postoperative day 7 stained with hematoxylin and eosin (original magnification ×10). The small black arrows indicate epithelial edge, and the large black arrowhead points to granulation tissue. Journal of Vascular Surgery 2011 54, 1430-1438DOI: (10.1016/j.jvs.2011.05.029) Copyright © 2011 Society for Vascular Surgery Terms and Conditions

Fig 4 A, Graph compares the average number of capillaries/high-powered field (HPF) in wounds in mice injected with lentivirus expressing peroxisomal biogenesis 2 (PEX2-LV) vs control mice injected with lentivirus expressing green fluorescent protein (GFP-LV). The average number of capillaries/HPF was 3.8 ± 1.1 in sections through wounds expressing PEX2 vs 6.9 ± 1.2 in control wounds (P < .007). The error bars show the mean ± standard error of the mean. B, In these representative sections of wounds (original magnification ×40), the white arrows indicate capillaries. Journal of Vascular Surgery 2011 54, 1430-1438DOI: (10.1016/j.jvs.2011.05.029) Copyright © 2011 Society for Vascular Surgery Terms and Conditions