Relationship Between The HIF-1αProtein Expression and Oxygen Partial Pressure of Muscle and Bone Marrow of Mice Hindlimb Ischemia_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 HUANGYing ^1,2 ,  ZHANGJian ^1,2 , CHENBing ^1,2 , YANGSheng-jia ^1,2 , YANChao ^1,2 , LILi-qiang ^1,2 , YANFeng ³

1. Vascular Department, Xuanwu Hospital of Capital Medical University, Beijing 100053, China;
2. Department of Vascular Surgery, Capital Medical University, Beijing 100053, China;
3. Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing 100053, China;

Corresponding?author：

ZHANGJian, Email: zhangyzh@public3.bta.net.cn

Keywords：

Limb ischemia; Oxygen tension; Hypoxia; hypoxia-inducible factor-1α

DOI：

10.7507/1007-9424.20150013

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the relationship between the oxygen partial pressure of mice hindlimb muscles with normal blood supply or ischemia and expression of HIF-1αprotein, and to provide a theoretical basis for the study of angiogenesis in vitro hypoxia. Methods Mice hind limb ischemia model were established, tissue oxygen tension of gastrocnemius muscle and bone marrow were measured by micro electrode at different time points of ischemia (24 hours, 1 week, 2 weeks, 3 weeks, and unoperated as control). Protein level of hypoxia inducible factor-1αand histological examination were performed on gastrocnemius muscle as well. Results The oxygen tension baselines of gastrocnemius muscle and femoral bone marrow was (47.78±4.37) mm Hg and (21±3.40) mm Hg, respectively. Muscle oxygen tension decreased significantly at all time points after modeling (P < 0.05), and reached lowest level in 1 week of ischemia. The inflammatory reaction was most serious and HIF-1αprotein reached highest level at the same time point. With the extension of ischemic time, the tissue oxygen tension recovered while HIF-1αlevel was down-regulated, however, There was no statistical correlation(r=-0.86, P > 0.05). Oxygen tension in bone marrow didn't show any significant change at all time points. Conclusions The expression level of HIF-1αprotein in ischemic tissue can reflect the degree of ischemic limb. The concept that physiological oxygen level differs in different tissue is highlighted, and may provide basis for ex vivo hypoxic research.

Citation： HUANGYing, ZHANGJian, CHENBing, YANGSheng-jia, YANChao, LILi-qiang, YANFeng. Relationship Between The HIF-1αProtein Expression and Oxygen Partial Pressure of Muscle and Bone Marrow of Mice Hindlimb Ischemia. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(1): 50-54. doi: 10.7507/1007-9424.20150013 Copy

1.	Semenza GL, Agani F, Booth G, et al. Structural and functional analysis of hypoxia-inducible factor-1. Kidney Int, 1997, 51(2):553-555.
2.	葉紅, 金咸.低氧誘導因子-1的結構、功能、調節及其與低氧信號轉導的關系.生理科學進展, 2001, 32(1):62-64.
3.	劉麗愉, 楊力芳, 曹亞.低氧誘導因子信號通路的研究新進展.國際病理科學與臨床雜志, 2011, 31(3):218-222.
4.	何覓春, 李靜, 趙春華.低氧對間充質干細胞的影響.中國實驗血液學雜志, 2007, 15(2):433-436.
5.	Semenza GL. Regulation of vascularization by hypoxia-inducible factor 1. Ann N Y Acad Sci, 2009, 1177:2-8.
6.	Couffinhal T, Silver M, Zheng LP, et al. Mouse model of angiogenesis. Am J Pathol, 1998, 152(6):1667-1679.
7.	Lawall H, Bramlage P, Amann B. Stem cell and progenitor cell therapy in peripheral artery disease. A critical appraisal. Thromb Haemost, 2010, 103(4):696-709.
8.	Ho TK, Abraham DJ, Black CM, et al. Hypoxia-inducible factor 1 in lower limb ischemia, Vascular, 2006, 14(6):321-327.
9.	Ho TK, RAjkumar V, Ponticos M, et al. Increased endogenous angiogenic response and hypoxia-inducible factor-1alpha inhuman critical limb ischemia. J Vasc Surg, 2006, 43(1):125-133.
10.	Abdollahi H, Harris LJ, Zhang P, et al. The role of hypoxia in stem cell differentiation and therapeutics. J Surg Res, 2011, 165(1):112-117.
11.	Thangarajah H, Vial IN, Chang E, et al. IFATS collection:Adipose stromal cells adopt a proangiogenice phenotype under the influence of hypoxia. Stem Cells, 2009, 27(1):266-274.
12.	王立維, 黃文, 趙渝.低氧培養對間充質干細胞生物學的影響.中國組織工程研究, 2012, 16(23):4329-4334.
13.	Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell, 2010, 40(2):294-309.
14.	Kurihara T, Westenskow PD, Friedlander M. Hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) signaling in the retina. Adv Exp Med Biol, 2014, 801:275-281.
15.	Brocato J, Chervona Y, Costa M. Molecular responses to hypoxia-inducible factor 1αand beyond. Mol Pharmacol, 2014, 85(5):651-657.
16.	Pattappa G, Thorpe SD, Jegard NC, et al. Continuous and uninterrupted oxygen tension influences the colony formation and oxidative metabolism of human mesenchymal stem cells. Tissue Eng Part C Methods, 2013, 19(1):68-79.
17.	Grayson WL, Zhao F, Bunnell B, et al. Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells. Biochem Biophys Res Commun, 2007, 358(3):948-953.
18.	Ren H, Cao Y, Zhao Q, et al. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochem Biophys Res Commun, 2006, 347(1):12-21.
19.	Itoigawa Y, Kishimoto KN, Okuno H, et al. Hypoxia induces adipogenic differentitation of myoblastic cell lines. Biochem Biophys Res Commun, 2010, 399(4):721-726.
20.	Dyson A, Singer M. Tissue oxygen tension monitoring:will it fill the void? Curr Opin Crit Care, 2011, 17(3):281-289.
21.	Hadjipanayi E, Brown RA, Mudera V, et al. Controlling physiological angiogenesis by hypoxia-induced signaling. J Control Release, 2010, 146(3):309-317.
22.	Harrison JS, Rameshwar P, Chang V, et al. Oxygen saturation in the bone marrow of healthy volunteers. Blood, 2002, 99(1):394.
23.	李晰, 辛世杰, 楊棟, 等.低氧誘導因子1α在大鼠下肢急性缺血中的表達.中華醫學雜志, 2012, 92(45):3232-3235.
24.	Ouma GO, Jonas RA, Usman MH, et al. Targets and delivery methods for therapeutic angiogenesis in peripheral artery disease. Vasc Med, 2012, 17(3):174-192.
25.	Bosch-Marce M, Okuyama H, Wesley JB, et al. Effects of aging and hypoxia-inducible factor-1 activity on angiogenic cell mobilization and recovery of perfusion after limb ischemia. Circ Res, 2007, 101(12):1310-1318.
26.	Oda M, Toba K, Kato K, et al. Hypocellularity and insufficient expression of angiogenic factors in implanted autologous bone marrow in patients with chronic critical limb ischemia. Heart Vessels, 2012, 27(1):38-45.

1. Semenza GL, Agani F, Booth G, et al. Structural and functional analysis of hypoxia-inducible factor-1. Kidney Int, 1997, 51(2):553-555.
2. 葉紅, 金咸.低氧誘導因子-1的結構、功能、調節及其與低氧信號轉導的關系.生理科學進展, 2001, 32(1):62-64.
3. 劉麗愉, 楊力芳, 曹亞.低氧誘導因子信號通路的研究新進展.國際病理科學與臨床雜志, 2011, 31(3):218-222.
4. 何覓春, 李靜, 趙春華.低氧對間充質干細胞的影響.中國實驗血液學雜志, 2007, 15(2):433-436.
5. Semenza GL. Regulation of vascularization by hypoxia-inducible factor 1. Ann N Y Acad Sci, 2009, 1177:2-8.
6. Couffinhal T, Silver M, Zheng LP, et al. Mouse model of angiogenesis. Am J Pathol, 1998, 152(6):1667-1679.
7. Lawall H, Bramlage P, Amann B. Stem cell and progenitor cell therapy in peripheral artery disease. A critical appraisal. Thromb Haemost, 2010, 103(4):696-709.
8. Ho TK, Abraham DJ, Black CM, et al. Hypoxia-inducible factor 1 in lower limb ischemia, Vascular, 2006, 14(6):321-327.
9. Ho TK, RAjkumar V, Ponticos M, et al. Increased endogenous angiogenic response and hypoxia-inducible factor-1alpha inhuman critical limb ischemia. J Vasc Surg, 2006, 43(1):125-133.
10. Abdollahi H, Harris LJ, Zhang P, et al. The role of hypoxia in stem cell differentiation and therapeutics. J Surg Res, 2011, 165(1):112-117.
11. Thangarajah H, Vial IN, Chang E, et al. IFATS collection:Adipose stromal cells adopt a proangiogenice phenotype under the influence of hypoxia. Stem Cells, 2009, 27(1):266-274.
12. 王立維, 黃文, 趙渝.低氧培養對間充質干細胞生物學的影響.中國組織工程研究, 2012, 16(23):4329-4334.
13. Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell, 2010, 40(2):294-309.
14. Kurihara T, Westenskow PD, Friedlander M. Hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) signaling in the retina. Adv Exp Med Biol, 2014, 801:275-281.
15. Brocato J, Chervona Y, Costa M. Molecular responses to hypoxia-inducible factor 1αand beyond. Mol Pharmacol, 2014, 85(5):651-657.
16. Pattappa G, Thorpe SD, Jegard NC, et al. Continuous and uninterrupted oxygen tension influences the colony formation and oxidative metabolism of human mesenchymal stem cells. Tissue Eng Part C Methods, 2013, 19(1):68-79.
17. Grayson WL, Zhao F, Bunnell B, et al. Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells. Biochem Biophys Res Commun, 2007, 358(3):948-953.
18. Ren H, Cao Y, Zhao Q, et al. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochem Biophys Res Commun, 2006, 347(1):12-21.
19. Itoigawa Y, Kishimoto KN, Okuno H, et al. Hypoxia induces adipogenic differentitation of myoblastic cell lines. Biochem Biophys Res Commun, 2010, 399(4):721-726.
20. Dyson A, Singer M. Tissue oxygen tension monitoring:will it fill the void? Curr Opin Crit Care, 2011, 17(3):281-289.
21. Hadjipanayi E, Brown RA, Mudera V, et al. Controlling physiological angiogenesis by hypoxia-induced signaling. J Control Release, 2010, 146(3):309-317.
22. Harrison JS, Rameshwar P, Chang V, et al. Oxygen saturation in the bone marrow of healthy volunteers. Blood, 2002, 99(1):394.
23. 李晰, 辛世杰, 楊棟, 等.低氧誘導因子1α在大鼠下肢急性缺血中的表達.中華醫學雜志, 2012, 92(45):3232-3235.
24. Ouma GO, Jonas RA, Usman MH, et al. Targets and delivery methods for therapeutic angiogenesis in peripheral artery disease. Vasc Med, 2012, 17(3):174-192.
25. Bosch-Marce M, Okuyama H, Wesley JB, et al. Effects of aging and hypoxia-inducible factor-1 activity on angiogenic cell mobilization and recovery of perfusion after limb ischemia. Circ Res, 2007, 101(12):1310-1318.
26. Oda M, Toba K, Kato K, et al. Hypocellularity and insufficient expression of angiogenic factors in implanted autologous bone marrow in patients with chronic critical limb ischemia. Heart Vessels, 2012, 27(1):38-45.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Relationship Between The HIF-1αProtein Expression and Oxygen Partial Pressure of Muscle and Bone Marrow of Mice Hindlimb Ischemia

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