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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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IFR treated-EPC transplantation improved blood perfusion in the ischemic hindlimb. (A) Representative images of hindlimb blood flow measured by laser Doppler and quantitative analysis of blood flow expressed as perfusion ratio of the ischemic to the contralateral (non-operated) hindlimb immediately after hindlimb ischemia surgery and 3 weeks after intramuscular injection of normal saline, EPC-treated with high glucose (EPC-HG), EPC-treated with high glucose and FIR therapy (EPC-HG + IFR), or EPC treated with high glucose and IFR and eNOS siRNA (EPC-HG + eNOS siRNA + IFR). (*p < 0.05 compared with control; #p < 0.05 compared with EPC-HG + IFR; n = 6).
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Figure 7: IFR treated-EPC transplantation improved blood perfusion in the ischemic hindlimb. (A) Representative images of hindlimb blood flow measured by laser Doppler and quantitative analysis of blood flow expressed as perfusion ratio of the ischemic to the contralateral (non-operated) hindlimb immediately after hindlimb ischemia surgery and 3 weeks after intramuscular injection of normal saline, EPC-treated with high glucose (EPC-HG), EPC-treated with high glucose and FIR therapy (EPC-HG + IFR), or EPC treated with high glucose and IFR and eNOS siRNA (EPC-HG + eNOS siRNA + IFR). (*p < 0.05 compared with control; #p < 0.05 compared with EPC-HG + IFR; n = 6).

Mentions: In the animals receiving normal saline, blood flow remained constant throughout the study, around 42% of that measured in the non-ischemic limb (42 ± 8%, four weeks after operation). In contrast, the mice transplanted with EPC and EPC received IFR therapy (30 mins) in high glucose medium (EPC-HG + IFR), but not EPC in high glucose medium without IFR therapy (EPC-HG) and EPC treated with high glucose and IFR and eNOS siRNA (EPC-HG + eNOS siRNA + IFR) already showed a significant improvement in blood flow by three weeks after EPCs implantation (both p < 0.05; Figure 7). Consistent with the measurements by Laser Doppler imaging, anti-CD31 immunostaining revealed that transplantation of EPC and EPC treated with IFR in high glucose conditions significantly increased the number of detectable capillaries in the ischemic muscle than mice received normal saline (both p < 0.05 compared to normal saline). However, treatment with eNOS siRNA abolished the benefit of IFR radiation in high glucose medium (IFR versus IFR + eNOS siRNA: 38.7 ± 4.7 versus 21.3 ± 3.7/HPF, p = 0.015, n = 6 per group).


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)

IFR treated-EPC transplantation improved blood perfusion in the ischemic hindlimb. (A) Representative images of hindlimb blood flow measured by laser Doppler and quantitative analysis of blood flow expressed as perfusion ratio of the ischemic to the contralateral (non-operated) hindlimb immediately after hindlimb ischemia surgery and 3 weeks after intramuscular injection of normal saline, EPC-treated with high glucose (EPC-HG), EPC-treated with high glucose and FIR therapy (EPC-HG + IFR), or EPC treated with high glucose and IFR and eNOS siRNA (EPC-HG + eNOS siRNA + IFR). (*p < 0.05 compared with control; #p < 0.05 compared with EPC-HG + IFR; n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472269&req=5

Figure 7: IFR treated-EPC transplantation improved blood perfusion in the ischemic hindlimb. (A) Representative images of hindlimb blood flow measured by laser Doppler and quantitative analysis of blood flow expressed as perfusion ratio of the ischemic to the contralateral (non-operated) hindlimb immediately after hindlimb ischemia surgery and 3 weeks after intramuscular injection of normal saline, EPC-treated with high glucose (EPC-HG), EPC-treated with high glucose and FIR therapy (EPC-HG + IFR), or EPC treated with high glucose and IFR and eNOS siRNA (EPC-HG + eNOS siRNA + IFR). (*p < 0.05 compared with control; #p < 0.05 compared with EPC-HG + IFR; n = 6).
Mentions: In the animals receiving normal saline, blood flow remained constant throughout the study, around 42% of that measured in the non-ischemic limb (42 ± 8%, four weeks after operation). In contrast, the mice transplanted with EPC and EPC received IFR therapy (30 mins) in high glucose medium (EPC-HG + IFR), but not EPC in high glucose medium without IFR therapy (EPC-HG) and EPC treated with high glucose and IFR and eNOS siRNA (EPC-HG + eNOS siRNA + IFR) already showed a significant improvement in blood flow by three weeks after EPCs implantation (both p < 0.05; Figure 7). Consistent with the measurements by Laser Doppler imaging, anti-CD31 immunostaining revealed that transplantation of EPC and EPC treated with IFR in high glucose conditions significantly increased the number of detectable capillaries in the ischemic muscle than mice received normal saline (both p < 0.05 compared to normal saline). However, treatment with eNOS siRNA abolished the benefit of IFR radiation in high glucose medium (IFR versus IFR + eNOS siRNA: 38.7 ± 4.7 versus 21.3 ± 3.7/HPF, p = 0.015, n = 6 per group).

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