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Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions.

Huang PH, Chen JW, Lin CP, Chen YH, Wang CH, Leu HB, Lin SJ - Cardiovasc Diabetol (2012)

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.

ABSTRACT

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.

Materials and 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.

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Effects of far infrared (IFR) therapy on blood flow recovery and new vessels formation in STZ-induced diabetic mice. (A) Representative results of laser Doppler measurements before operation and 4 weeks after hindlimb ischemia surgery in wild-type mice, control (vehicle), IFR therapy, and IFR + NG-nitro-L-arginine methyl ester (L-NAME) mice. Color scale illustrates blood flow variations from minimal (dark blue) to maximal (red) values. Arrows indicate ischemic (right) limb after hindlimb ischemia surgery. Doppler perfusion ratio (ischemic/non-ischemic hind limb) over time in the different groups. Administration of L-NAME in drinking water abolished the beneficial effect of IFR therapy in diabetic mice. (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-FIR; n = 6) (B) Mice were sacrificed 3 weeks after surgery and capillaries in the ischemic muscles were visualized by anti-CD31 immunostaining. Results are mean ± standard error of mean (SEM). (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-IFR; n = 6).
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Figure 1: Effects of far infrared (IFR) therapy on blood flow recovery and new vessels formation in STZ-induced diabetic mice. (A) Representative results of laser Doppler measurements before operation and 4 weeks after hindlimb ischemia surgery in wild-type mice, control (vehicle), IFR therapy, and IFR + NG-nitro-L-arginine methyl ester (L-NAME) mice. Color scale illustrates blood flow variations from minimal (dark blue) to maximal (red) values. Arrows indicate ischemic (right) limb after hindlimb ischemia surgery. Doppler perfusion ratio (ischemic/non-ischemic hind limb) over time in the different groups. Administration of L-NAME in drinking water abolished the beneficial effect of IFR therapy in diabetic mice. (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-FIR; n = 6) (B) Mice were sacrificed 3 weeks after surgery and capillaries in the ischemic muscles were visualized by anti-CD31 immunostaining. Results are mean ± standard error of mean (SEM). (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-IFR; n = 6).

Mentions: Local IFR therapy was given in STZ-induced diabetic mice for 30 min twice per day for 2 weeks after the surgery, and wild-type and diabetic control mice were placed on a heating plate at 34°C for 30 min twice daily to avoid the thermal effect in this study. As shown in Figure 1A, the STZ-induced diabetic mice without IFR therapy showed delayed blood flow recovery after ischemia surgery compared with that in wild-type mice, as determined by Laser Doppler imaging. Meanwhile, the repeated IFR therapy significantly improved blood flow recovery by 48% in STZ-induced diabetic mice (n = 6 per group). However, the benefit of local IFR radiation was significantly abolished after treatment with the eNOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/ml in drinking water). Consistent with the measurements by Laser Doppler imaging, anti-CD31 immunostaining revealed that repeated FIR radiation increased the number of detectable capillaries in the ischemic muscle in STZ-induced diabetic mice (control versus IFR: 38.8 ± 1.8 versus 48.7 ± 2.4/HPF, p = 0.008) (Figure 1B). However, administration of L-NAME abolished the benefit of IFR radiation (detectable capillaries, IFR versus IFR + L-NAME: 48.7 ± 2.4 versus 34.8 ± 1.7/HPF, p = 0.001).


Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions.

Huang PH, Chen JW, Lin CP, Chen YH, Wang CH, Leu HB, Lin SJ - Cardiovasc Diabetol (2012)

Effects of far infrared (IFR) therapy on blood flow recovery and new vessels formation in STZ-induced diabetic mice. (A) Representative results of laser Doppler measurements before operation and 4 weeks after hindlimb ischemia surgery in wild-type mice, control (vehicle), IFR therapy, and IFR + NG-nitro-L-arginine methyl ester (L-NAME) mice. Color scale illustrates blood flow variations from minimal (dark blue) to maximal (red) values. Arrows indicate ischemic (right) limb after hindlimb ischemia surgery. Doppler perfusion ratio (ischemic/non-ischemic hind limb) over time in the different groups. Administration of L-NAME in drinking water abolished the beneficial effect of IFR therapy in diabetic mice. (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-FIR; n = 6) (B) Mice were sacrificed 3 weeks after surgery and capillaries in the ischemic muscles were visualized by anti-CD31 immunostaining. Results are mean ± standard error of mean (SEM). (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-IFR; n = 6).
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Figure 1: Effects of far infrared (IFR) therapy on blood flow recovery and new vessels formation in STZ-induced diabetic mice. (A) Representative results of laser Doppler measurements before operation and 4 weeks after hindlimb ischemia surgery in wild-type mice, control (vehicle), IFR therapy, and IFR + NG-nitro-L-arginine methyl ester (L-NAME) mice. Color scale illustrates blood flow variations from minimal (dark blue) to maximal (red) values. Arrows indicate ischemic (right) limb after hindlimb ischemia surgery. Doppler perfusion ratio (ischemic/non-ischemic hind limb) over time in the different groups. Administration of L-NAME in drinking water abolished the beneficial effect of IFR therapy in diabetic mice. (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-FIR; n = 6) (B) Mice were sacrificed 3 weeks after surgery and capillaries in the ischemic muscles were visualized by anti-CD31 immunostaining. Results are mean ± standard error of mean (SEM). (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-IFR; n = 6).
Mentions: Local IFR therapy was given in STZ-induced diabetic mice for 30 min twice per day for 2 weeks after the surgery, and wild-type and diabetic control mice were placed on a heating plate at 34°C for 30 min twice daily to avoid the thermal effect in this study. As shown in Figure 1A, the STZ-induced diabetic mice without IFR therapy showed delayed blood flow recovery after ischemia surgery compared with that in wild-type mice, as determined by Laser Doppler imaging. Meanwhile, the repeated IFR therapy significantly improved blood flow recovery by 48% in STZ-induced diabetic mice (n = 6 per group). However, the benefit of local IFR radiation was significantly abolished after treatment with the eNOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/ml in drinking water). Consistent with the measurements by Laser Doppler imaging, anti-CD31 immunostaining revealed that repeated FIR radiation increased the number of detectable capillaries in the ischemic muscle in STZ-induced diabetic mice (control versus IFR: 38.8 ± 1.8 versus 48.7 ± 2.4/HPF, p = 0.008) (Figure 1B). However, administration of L-NAME abolished the benefit of IFR radiation (detectable capillaries, IFR versus IFR + L-NAME: 48.7 ± 2.4 versus 34.8 ± 1.7/HPF, p = 0.001).

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.

ABSTRACT

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.

Materials and 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.

Show MeSH
Related in: MedlinePlus