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Sonic hedgehog induces arteriogenesis in diabetic vasa nervorum and restores function in diabetic neuropathy.
Arterioscler Thromb Vasc Biol. 2004 Nov; 24(11):2102-7.AT

Abstract

OBJECTIVE

The embryonic morphogen sonic hedgehog (SHh) has been shown to induce neovascularization of ischemic tissue but has not been shown to play a role in regulating vascular nerve supply. Accordingly, we investigated the hypothesis that systemic injection of SHh protein could improve nerve blood flow and function in diabetic neuropathy (DN).

METHODS AND RESULTS

Twelve weeks after induction of diabetes with streptozotocin, motor and sensory nerve conduction velocities (MCV and SCV) of the sciatic nerves were significantly reduced in diabetic rats. SHh-treated diabetic rats demonstrated marked improvement of both MCV and SCV (P<0.05). Laser Doppler perfusion imaging showed that nerve blood flow was significantly reduced in the diabetic rats but was restored in SHh-treated diabetic rats (P<0.05 versus diabetic saline-treated rats) to levels similar to those achieved with vascular endothelial growth factor-2 (VEGF-2) gene therapy. In vivo perfusion of Bandeuraea simplicifolia (BS)-1 lectin showed marked reduction in the vasa nervora in diabetic sciatic nerves but restoration of nerve vasculature to nondiabetic levels in the SHh-treated and plasmid DNA encoding human VEGF-2 (phVEGF-2)-treated diabetic nerves. Interestingly, the SHh-induced vasculature was characterized by larger diameter and more smooth muscle cell-containing vessels, compared with VEGF-2 gene-treated diabetic rats.

CONCLUSIONS

These data indicate that Shh induces arteriogenesis and restores nerve function in DN.

Authors+Show Affiliations

Division of Cardiovascular Research, St. Elizabeth Medical Center Boston, Boston, MA 02135, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15358602

Citation

Kusano, Kengo F., et al. "Sonic Hedgehog Induces Arteriogenesis in Diabetic Vasa Nervorum and Restores Function in Diabetic Neuropathy." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 11, 2004, pp. 2102-7.
Kusano KF, Allendoerfer KL, Munger W, et al. Sonic hedgehog induces arteriogenesis in diabetic vasa nervorum and restores function in diabetic neuropathy. Arterioscler Thromb Vasc Biol. 2004;24(11):2102-7.
Kusano, K. F., Allendoerfer, K. L., Munger, W., Pola, R., Bosch-Marce, M., Kirchmair, R., Yoon, Y. S., Curry, C., Silver, M., Kearney, M., Asahara, T., & Losordo, D. W. (2004). Sonic hedgehog induces arteriogenesis in diabetic vasa nervorum and restores function in diabetic neuropathy. Arteriosclerosis, Thrombosis, and Vascular Biology, 24(11), 2102-7.
Kusano KF, et al. Sonic Hedgehog Induces Arteriogenesis in Diabetic Vasa Nervorum and Restores Function in Diabetic Neuropathy. Arterioscler Thromb Vasc Biol. 2004;24(11):2102-7. PubMed PMID: 15358602.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sonic hedgehog induces arteriogenesis in diabetic vasa nervorum and restores function in diabetic neuropathy. AU - Kusano,Kengo F, AU - Allendoerfer,Karen L, AU - Munger,William, AU - Pola,Roberto, AU - Bosch-Marce,Marta, AU - Kirchmair,Rudolf, AU - Yoon,Young-sup, AU - Curry,Cynthia, AU - Silver,Marcy, AU - Kearney,Marianne, AU - Asahara,Takayuki, AU - Losordo,Douglas W, Y1 - 2004/09/09/ PY - 2004/9/11/pubmed PY - 2005/6/1/medline PY - 2004/9/11/entrez SP - 2102 EP - 7 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler. Thromb. Vasc. Biol. VL - 24 IS - 11 N2 - OBJECTIVE: The embryonic morphogen sonic hedgehog (SHh) has been shown to induce neovascularization of ischemic tissue but has not been shown to play a role in regulating vascular nerve supply. Accordingly, we investigated the hypothesis that systemic injection of SHh protein could improve nerve blood flow and function in diabetic neuropathy (DN). METHODS AND RESULTS: Twelve weeks after induction of diabetes with streptozotocin, motor and sensory nerve conduction velocities (MCV and SCV) of the sciatic nerves were significantly reduced in diabetic rats. SHh-treated diabetic rats demonstrated marked improvement of both MCV and SCV (P<0.05). Laser Doppler perfusion imaging showed that nerve blood flow was significantly reduced in the diabetic rats but was restored in SHh-treated diabetic rats (P<0.05 versus diabetic saline-treated rats) to levels similar to those achieved with vascular endothelial growth factor-2 (VEGF-2) gene therapy. In vivo perfusion of Bandeuraea simplicifolia (BS)-1 lectin showed marked reduction in the vasa nervora in diabetic sciatic nerves but restoration of nerve vasculature to nondiabetic levels in the SHh-treated and plasmid DNA encoding human VEGF-2 (phVEGF-2)-treated diabetic nerves. Interestingly, the SHh-induced vasculature was characterized by larger diameter and more smooth muscle cell-containing vessels, compared with VEGF-2 gene-treated diabetic rats. CONCLUSIONS: These data indicate that Shh induces arteriogenesis and restores nerve function in DN. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/15358602/Sonic_hedgehog_induces_arteriogenesis_in_diabetic_vasa_nervorum_and_restores_function_in_diabetic_neuropathy_ L2 - http://www.ahajournals.org/doi/full/10.1161/01.ATV.0000144813.44650.75?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -