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Shock wave treatment induces angiogenesis and mobilizes endogenous CD31/CD34- positive endothelial cells in a hindlimb ischemia model: Implications for.

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Presentation on theme: "Shock wave treatment induces angiogenesis and mobilizes endogenous CD31/CD34- positive endothelial cells in a hindlimb ischemia model: Implications for."— Presentation transcript:

1 Shock wave treatment induces angiogenesis and mobilizes endogenous CD31/CD34- positive endothelial cells in a hindlimb ischemia model: Implications for angiogenesis and vasculogenesis  Can Tepeköylü, MD, Feng-Sheng Wang, PhD, Radoslaw Kozaryn, MS, Karin Albrecht-Schgoer, PhD, Markus Theurl, MD, Wolfgang Schaden, MD, Huei-Jin Ke, Yaju Yang, Rudolf Kirchmair, MD, Michael Grimm, MD, Ching-Jen Wang, MD, Johannes Holfeld, MD  The Journal of Thoracic and Cardiovascular Surgery  Volume 146, Issue 4, Pages (October 2013) DOI: /j.jtcvs Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

2 Figure 1 Circulating CD31/CD34-positive endothelial cells. A, Fluorescence activated cell sorting (FACS) analysis of peripheral blood revealed significantly greater numbers of circulating CD31/CD34-positive endothelial cells 24 hours after shock wave treatment (SWT), indicating early mobilization of endothelial progenitor cell, most probably from bone marrow. Number of endothelial progenitor cells still elevated after 1 week; however, 6 weeks after SWT, no difference found between treatment and control (CTR) group. ∗P < .05. B, Representative views from fluorescence activated cell sorting 24 hours after SWT showing greater numbers of endothelial progenitor cells in treatment group. FITC, Fluorescein isothiocyanate. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

3 Figure 2 Increase of angiogenic and chemoattractive factors in treated muscle. A, Expression of hypoxia-inducible factor 1α (HIF-1α) regulating stromal cell-derived factor-1 (SDF-1) significantly elevated in treatment group 24 hours and 6 weeks after shock wave therapy (SWT). In line with these findings, B, SDF-1 and C, its receptor C-X-C chemokine receptor type 4 (CXCR-4) also significantly upregulated. Vascular endothelial growth factor (VEGF)-A mRNA showed increased levels at 24 hours after treatment in treatment and control (CTR) groups. D, However, levels remain elevated in treatment group even at 6 weeks after SWT. E, VEGF protein concentration (given as pg/mg protein) showed significant increase in treatment group compared with untreated controls. ∗P < .05. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

4 Figure 3 Increase of capillary density in treated ischemic muscle. A, Immunohistochemical staining for CD31-positive cells revealed significantly greater numbers of capillaries 24 hours and 6 weeks after shock wave therapy (SWT). Data presented as percentage of total cells per high power field. B, Significantly more proliferating cells found in treatment group, as shown by proliferating cell nuclear antigen (PCNA). In addition to hypothesis of endothelial progenitor recruitment for vasculogenesis, this indicates additional vessel sprouting in parallel. C, Representative views of immunohistochemical (IHC) staining for CD31 (endothelial cells) and PCNA (proliferating cells). Magnification ×400. ∗P < .05. CTR, Control. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

5 Figure 4 Restoration of blood perfusion. Blood perfusion of hind limbs measured by laser Doppler perfusion imaging 6 weeks after treatment. A, Blood perfusion of sham-operated rat; B, Representative view of perfusion in untreated control (CTR); and C, representative view of perfusion of shock wave therapy (SWT) rat. Blood perfusion clearly restored in treatment group. D, Quantification of measurements expressed as ratio of right (operated, ischemic) leg to left (nonoperated, nonischemic) leg revealing significant improvement in treatment group compared with untreated controls. ∗P < .05. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

6 Figure 5 Functional recovery of ischemic limbs. Functional assessment performed by catwalk gait analysis 6 weeks after treatment showing restored blood perfusion resulted in recovery of walking pattern in shock wave therapy (SWT) group. Significant improvement found in A, swing speed of hind limbs and B, their maximum print intensity. Recovery also seen in C, mean stride length and D, mean print area. E, More physiologic footprint of treatment animal (Right) compared with typically malfunctioning step of control (CTR) animal (Left). F, Walking regularity clearly restored 6 weeks after SWT. ∗P < .05. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

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