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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 IFR radiation on oxidative stress, EPC mobilization after hindlimb ischemia and tissue homing in STZ-induced diabetic mice. (A) Effect of IFR on oxidative stress in ischemic muscles of STZ-induced diabetic mice. Nitrotyrosine (n = 4 per group) immunostaining of ischemic muscles extracted on day 21 in control (vehicle), and in mice that had received IFR radiation. (*p < 0.05 compared with DM-control) (B) EPCs (defined as Sca-1+/Flk-1+ cells) mobilization after tissue ischemia was determined by flow cytometry in STZ-induced diabetic mice given the vehicle, IFR or IFR + L-NAME. (*p < 0.05 compared with WT-baseline; n = 6 per group) (C) STZ-induced diabetes was created in FVB mice that received eGFP mouse bone marrow cells. By immunofluorescence staining, STZ-induced diabetic mice in IFR group had more GFP+/CD31+ double-positive cells in ischemic muscle than those in the vehicle group. (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-FIR; n = 6).
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Figure 2: Effects of IFR radiation on oxidative stress, EPC mobilization after hindlimb ischemia and tissue homing in STZ-induced diabetic mice. (A) Effect of IFR on oxidative stress in ischemic muscles of STZ-induced diabetic mice. Nitrotyrosine (n = 4 per group) immunostaining of ischemic muscles extracted on day 21 in control (vehicle), and in mice that had received IFR radiation. (*p < 0.05 compared with DM-control) (B) EPCs (defined as Sca-1+/Flk-1+ cells) mobilization after tissue ischemia was determined by flow cytometry in STZ-induced diabetic mice given the vehicle, IFR or IFR + L-NAME. (*p < 0.05 compared with WT-baseline; n = 6 per group) (C) STZ-induced diabetes was created in FVB mice that received eGFP mouse bone marrow cells. By immunofluorescence staining, STZ-induced diabetic mice in IFR group had more GFP+/CD31+ double-positive cells in ischemic muscle than those in the vehicle group. (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-FIR; n = 6).

Mentions: To further evaluate the effect of IFR therapy on oxidative stress on ischemic muscles, immunostaining against nitrotyrosine was performed. As shown on Figure 2A, assessed by nitrotyrosine staining, a significant reduction of oxidative stress levels in ischemic muscles was noted in diabetic mice that received IFR therapy.


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 IFR radiation on oxidative stress, EPC mobilization after hindlimb ischemia and tissue homing in STZ-induced diabetic mice. (A) Effect of IFR on oxidative stress in ischemic muscles of STZ-induced diabetic mice. Nitrotyrosine (n = 4 per group) immunostaining of ischemic muscles extracted on day 21 in control (vehicle), and in mice that had received IFR radiation. (*p < 0.05 compared with DM-control) (B) EPCs (defined as Sca-1+/Flk-1+ cells) mobilization after tissue ischemia was determined by flow cytometry in STZ-induced diabetic mice given the vehicle, IFR or IFR + L-NAME. (*p < 0.05 compared with WT-baseline; n = 6 per group) (C) STZ-induced diabetes was created in FVB mice that received eGFP mouse bone marrow cells. By immunofluorescence staining, STZ-induced diabetic mice in IFR group had more GFP+/CD31+ double-positive cells in ischemic muscle than those in the vehicle group. (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-FIR; n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: Effects of IFR radiation on oxidative stress, EPC mobilization after hindlimb ischemia and tissue homing in STZ-induced diabetic mice. (A) Effect of IFR on oxidative stress in ischemic muscles of STZ-induced diabetic mice. Nitrotyrosine (n = 4 per group) immunostaining of ischemic muscles extracted on day 21 in control (vehicle), and in mice that had received IFR radiation. (*p < 0.05 compared with DM-control) (B) EPCs (defined as Sca-1+/Flk-1+ cells) mobilization after tissue ischemia was determined by flow cytometry in STZ-induced diabetic mice given the vehicle, IFR or IFR + L-NAME. (*p < 0.05 compared with WT-baseline; n = 6 per group) (C) STZ-induced diabetes was created in FVB mice that received eGFP mouse bone marrow cells. By immunofluorescence staining, STZ-induced diabetic mice in IFR group had more GFP+/CD31+ double-positive cells in ischemic muscle than those in the vehicle group. (*p < 0.05 compared with DM-control; #p < 0.05 compared with DM-FIR; n = 6).
Mentions: To further evaluate the effect of IFR therapy on oxidative stress on ischemic muscles, immunostaining against nitrotyrosine was performed. As shown on Figure 2A, assessed by nitrotyrosine staining, a significant reduction of oxidative stress levels in ischemic muscles was noted in diabetic mice that received IFR therapy.

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