Chronic intermittent hypobaric hypoxia attenuates ischemic limb injury by promoting angiogenesis in mice

• Published in: Canadian journal of physiology and pharmacology 2021-11, Vol.99 (11), p.1191-1198
• Main Authors: Tian, Yanming, Zhang, Li, Guo, Xinqi, Gao, Zheng, Zhang, Yi, Zhang, Liping, Hou, Zhiyong
• Format: Article
• Language: English
• Subjects: Altitude; Angiogenesis; angiogenèse; Animal models; Animals; Antigens, CD34; Blood flow; Care and treatment; CD34 antigen; chronic intermittent hypobaric hypoxia; Contraction; Disease Models, Animal; Doppler effect; Extremities (Anatomy); Femoral artery; Fibrosis; Gastrocnemius muscle; Health aspects; HIF1α; hind-limb ischemia; Hindlimb - blood supply; Hypoxia; Hypoxia - physiopathology; hypoxia inducible factor 1α; Hypoxia-Inducible Factor 1, alpha Subunit; hypoxie intermittente chronique hypobarique; Immunohistochemistry; Ischemia; Ischemia - physiopathology; Ischemia - therapy; ischémie dans une patte postérieure; Male; Mice; Mice, Inbred C57BL; Morphology; Muscle Contraction; muscle squelettique; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Neovascularization; Neovascularization, Physiologic - genetics; Occlusion; Perfusion; Platelet Endothelial Cell Adhesion Molecule-1; skeletal muscle
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2021-0047

This study aimed to evaluate the protective effect of chronic intermittent hypobaric hypoxia (CIHH) against limb ischemic injury. C57BL/6 mice were randomly divided into three groups: limb ischemic injury group (Ischemia, induced by ligation and excision of the left femoral artery), limb ischemia following CIHH pretreatment group (CIHH+Ischemia, simulated a 5000 m altitude hypoxia, 6 h per day for 28 days, before induction of hind-limb ischemia), and sham group (Sham). The blood flow in the mouse models of hind-limb ischemia was examined using laser doppler imaging. The functional and morphological performance of ischemic muscle was evaluated using contraction force and hematoxylin–eosin and Masson’s trichrome staining. Angiogenesis was determined by immunohistochemistry staining of the endothelial markers CD31 and CD34. The protein expressions of angiogenesis-related genes were detected using Western blot assay. Chronic ischemia resulted in reduced blood perfusion, decreased contraction tension, and morphological destruction in gastrocnemius muscle. CIHH pretreatment increased the contractile force and muscle fiber diameter and decreased necrosis and fibrosis of the ischemic muscle. Also, CIHH significantly increased the density of CD31 + and CD34 + cells and promoted the expression of angiogenesis-related molecules in ischemic muscle. These data demonstrate that CIHH has a protective effect against chronic limb ischemia by promoting angiogenesis.