Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions.
BACKGROUND
Far infra-red (IFR) therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC) and EPC-related vasculogenesis remain unclear. We hypothesized that IFR radiation can restore blood flow recovery in ischemic hindlimb in diabetic mice by enhancement of EPCs functions and homing process.


METHODS
Starting at 4 weeks after the onset of diabetes, unilateral hindlimb ischemia was induced in streptozotocin (STZ)-induced diabetic mice, which were divided into control and IFR therapy groups (n = 6 per group). The latter mice were placed in an IFR dry sauna at 34°C for 30 min once per day for 5 weeks.


RESULTS
Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group. Flow cytometry analysis showed impaired EPCs (Sca-1(+)/Flk-1(+)) mobilization after ischemia surgery in diabetic mice with or without IFR therapy (n = 6 per group). However, as compared to those in the control group, bone marrow-derived EPCs differentiated into endothelial cells defined as GFP(+)/CD31(+) double-positive cells were significantly increased in ischemic tissue around the vessels in diabetic mice that received IFR radiation. In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H(2)O(2) production. Nude mice received human EPCs treated with IFR in high glucose medium showed a significant improvement in blood flow recovery in ischemic limb compared to those without IFR therapy. IFR therapy promoted blood flow recovery and new vessel formation in STZ-induced diabetic mice.


CONCLUSIONS
Administration of IFR therapy promoted collateral flow recovery and new vessel formation in STZ-induced diabetic mice, and these beneficial effects may derive from enhancement of EPC functions and homing process.
Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.
Po-Hsun
PH
Huang
Jaw-Wen
JW
Chen
Chih-Pei
CP
Lin
Ying-Hwa
YH
Chen
Chao-Hung
CH
Wang
Hsin-Bang
HB
Leu
Shing-Jong
SJ
Lin
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D003097:Collateral Circulation; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism / Q000528:radiation effects* / Q000637:transplantation; D005434:Flow Cytometry; D006614:Hindlimb; D006801:Humans; D007259:Infrared Rays / Q000627:therapeutic use*; D007511:Ischemia / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic / Q000528:radiation effects*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000528:radiation effects; D055420:Perfusion Imaging / Q000379:methods; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012039:Regional Blood Flow; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000528:radiation effects*; D013997:Time Factors; D018608:Ultrasonography, Doppler; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000950:Antigens, Ly; D015415:Biomarkers; D001786:Blood Glucose; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D040301:Vascular Endothelial Growth Factor Receptor-2