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Study · Animal study (in vivo) · mouse · 2019

13 results

Carnosine Supplementation Enhances Post Ischemic Hind Limb Revascularization.

Boakye AA, Zhang D, Guo L, Zheng Y, Hoetker D, Zhao J, Posa DK, Ng CK, Zheng H, Kumar A, Kumar V, Wempe MF, Bhatnagar A, Conklin DJ, Baba SP

Frontiers in physiology2 Jul 2019Cited by 24 (Europe PMC)

Summary

High (millimolar) concentrations of the histidine containing dipeptide - carnosine (β-alanine-L-histidine) are present in the skeletal muscle. The dipeptide has been shown to buffer intracellular pH, chelate transition metals, and scavenge lipid peroxidation products; however, its role in protecting against tissue injury remains unclear. In this study, we tested the hypothesis that carnosine protects against post ischemia by augmenting HIF-1α angiogenic signaling by Fe2+ chelation. We found that wild type (WT) C57BL/6 mice, subjected to hind limb ischemia (HLI) and supplemented with carnosine (1g/L) in drinking water, had improved blood flow recovery and limb function, enhanced revascularization and regeneration of myocytes compared with HLI mice placed on water alone. Carnosine supplementation enhanced the bioavailability of carnosine in the ischemic limb, which was accompanied by increased expression of proton-coupled oligopeptide transporters. Consistent with our hypothesis, carnosine supplementation augmented HIF-1α and VEGF expression in the ischemic limb and the mobilization of proangiogenic Flk-1+/Sca-1+ cells into circulation. Pretreatment of murine myoblast (C2C12) cells with octyl-D-carnosine or carnosine enhanced HIF-1α protein expression, VEGF mRNA levels and VEGF release under hypoxic conditions. Similarly pretreatment of WT C57/Bl6 mice with carnosine showed enhanced blood flow in the ischemic limb following HLI surgery. In contrast, pretreatment of hypoxic C2C12 cells with methylcarcinine, a carnosine analog, lacking Fe2+ chelating capacity, had no effect on HIF-1α levels and VEGF release. Collectively, these data suggest that carnosine promotes post ischemic revascularization via augmentation of pro-angiogenic HIF-1α/VEGF signaling, possibly by Fe2+ chelation.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study13

13 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice with hind limb ischemia, carnosine improved blood flow recovery compared with water alone.

    In plain wordsIn mice with hind limb ischemia, carnosine improved blood flow recovery compared with water alone.

    Outcome
    IncreaseBlood flow recovery
    Study

    mousen: not reported in source

    WT C57BL/6 mice with hind limb ischemia
    Comparator
    Water alone
    Outcome group
    Vascular function · Cardiovascular
    Studied dose
    1g/L · drinking waterAs given in this study (mouse).

    Source sentences

    Summary
    We found that wild type (WT) C57BL/6 mice, subjected to hind limb ischemia (HLI) and supplemented with carnosine (1g/L) in drinking water, had improved blood flow recovery and limb function, enhanced revascularization and regeneration of myocytes compared with HLI mice placed on water alone.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice with hind limb ischemia, carnosine improved limb function compared with water alone.

    In plain wordsIn mice with hind limb ischemia, carnosine improved limb function compared with water alone.

    Outcome
    IncreaseLimb function
    Study

    mousen: not reported in source

    WT C57BL/6 mice with hind limb ischemia
    Comparator
    Water alone
    Outcome group
    Exercise and physical function · Cardiovascular
    Studied dose
    1g/L · drinking waterAs given in this study (mouse).

    Source sentences

    Summary
    We found that wild type (WT) C57BL/6 mice, subjected to hind limb ischemia (HLI) and supplemented with carnosine (1g/L) in drinking water, had improved blood flow recovery and limb function, enhanced revascularization and regeneration of myocytes compared with HLI mice placed on water alone.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In mice with hind limb ischemia, carnosine enhanced revascularization compared with water alone.

    In plain wordsIn mice with hind limb ischemia, carnosine enhanced new blood vessel formation compared with water alone.

    Outcome
    IncreaseRevascularization
    Study

    mousen: not reported in source

    WT C57BL/6 mice with hind limb ischemia
    Comparator
    Water alone
    Outcome group
    Vascular function · Cardiovascular
    Studied dose
    1g/L · drinking waterAs given in this study (mouse).

    Source sentences

    Summary
    We found that wild type (WT) C57BL/6 mice, subjected to hind limb ischemia (HLI) and supplemented with carnosine (1g/L) in drinking water, had improved blood flow recovery and limb function, enhanced revascularization and regeneration of myocytes compared with HLI mice placed on water alone.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In mice with hind limb ischemia, carnosine enhanced myocyte regeneration compared with water alone.

    In plain wordsIn mice with hind limb ischemia, carnosine enhanced muscle cell regeneration compared with water alone.

    Outcome
    IncreaseMyocyte regeneration
    Study

    mousen: not reported in source

    WT C57BL/6 mice with hind limb ischemia
    Comparator
    Water alone
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    1g/L · drinking waterAs given in this study (mouse).

    Source sentences

    Summary
    We found that wild type (WT) C57BL/6 mice, subjected to hind limb ischemia (HLI) and supplemented with carnosine (1g/L) in drinking water, had improved blood flow recovery and limb function, enhanced revascularization and regeneration of myocytes compared with HLI mice placed on water alone.
  5. 05AnimalAnimal study (in vivo)Pharmacokinetics

    In mice with hind limb ischemia, carnosine supplementation enhanced carnosine bioavailability in the ischemic limb.

    In plain wordsIn mice with hind limb ischemia, carnosine supplementation increased carnosine availability in the affected limb.

    Outcome
    IncreaseIschemic limb carnosine bioavailability
    Study

    mousen: not reported in source

    WT C57BL/6 mice with hind limb ischemia
    Comparator
    Water alone
    Outcome group
    Pharmacokinetics · Cardiovascular
    Studied dose
    1g/L · drinking waterAs given in this study (mouse).

    Source sentences

    Summary
    Carnosine supplementation enhanced the bioavailability of carnosine in the ischemic limb, which was accompanied by increased expression of proton-coupled oligopeptide transporters.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In mice with hind limb ischemia, carnosine supplementation accompanied increased proton-coupled oligopeptide transporter expression.

    In plain wordsIn mice with hind limb ischemia, carnosine supplementation accompanied increased peptide transporter expression.

    Outcome
    IncreaseProton-coupled oligopeptide transporter expression
    Study

    mousen: not reported in source

    WT C57BL/6 mice with hind limb ischemia
    Comparator
    Water alone
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    1g/L · drinking waterAs given in this study (mouse).

    Source sentences

    Summary
    Carnosine supplementation enhanced the bioavailability of carnosine in the ischemic limb, which was accompanied by increased expression of proton-coupled oligopeptide transporters.
  7. 07AnimalAnimal study (in vivo)Mechanism

    In mice with hind limb ischemia, carnosine augmented HIF-1α expression in the ischemic limb.

    In plain wordsIn mice with hind limb ischemia, carnosine increased HIF-1α expression in the affected limb.

    Outcome
    IncreaseHIF-1α expression
    Study

    mousen: not reported in source

    WT C57BL/6 mice with hind limb ischemia
    Comparator
    Water alone
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    1g/L · drinking waterAs given in this study (mouse).

    Source sentences

    Summary
    Consistent with our hypothesis, carnosine supplementation augmented HIF-1α and VEGF expression in the ischemic limb and the mobilization of proangiogenic Flk-1+/Sca-1+ cells into circulation.
  8. 08AnimalAnimal study (in vivo)Mechanism

    In mice with hind limb ischemia, carnosine augmented VEGF expression in the ischemic limb.

    In plain wordsIn mice with hind limb ischemia, carnosine increased VEGF expression in the affected limb.

    Outcome
    IncreaseVEGF expression
    Study

    mousen: not reported in source

    WT C57BL/6 mice with hind limb ischemia
    Comparator
    Water alone
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    1g/L · drinking waterAs given in this study (mouse).

    Source sentences

    Summary
    Consistent with our hypothesis, carnosine supplementation augmented HIF-1α and VEGF expression in the ischemic limb and the mobilization of proangiogenic Flk-1+/Sca-1+ cells into circulation.
  9. 09AnimalAnimal study (in vivo)Mechanism

    In mice with hind limb ischemia, carnosine augmented mobilization of proangiogenic Flk-1-positive/Sca-1-positive cells into circulation.

    In plain wordsIn mice with hind limb ischemia, carnosine increased movement of vessel-forming cells into circulation.

    Outcome
    IncreaseCirculating proangiogenic cells
    Study

    mousen: not reported in source

    WT C57BL/6 mice with hind limb ischemia
    Comparator
    Water alone
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    1g/L · drinking waterAs given in this study (mouse).

    Source sentences

    Summary
    Consistent with our hypothesis, carnosine supplementation augmented HIF-1α and VEGF expression in the ischemic limb and the mobilization of proangiogenic Flk-1+/Sca-1+ cells into circulation.
  10. 10AnimalAnimal study (in vivo)Efficacy outcome

    In WT C57/Bl6 mice, carnosine pretreatment enhanced ischemic limb blood flow after hind limb ischemia surgery.

    In plain wordsIn mice, carnosine pretreatment enhanced blood flow in the affected limb after ischemia surgery.

    Outcome
    IncreaseBlood flow after pretreatment
    Study

    mousen: not reported in source

    WT C57BL/6 mice with hind limb ischemia
    Outcome group
    Vascular function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Similarly pretreatment of WT C57/Bl6 mice with carnosine showed enhanced blood flow in the ischemic limb following HLI surgery.
  11. 11LabIn vitro (cells)Mechanism

    In hypoxic C2C12 cells, carnosine pretreatment enhanced HIF-1α protein expression.

    In plain wordsIn cells under low oxygen, carnosine pretreatment increased HIF-1α protein expression.

    Outcome
    IncreaseHIF-1α protein expression
    Study

    mousen: not reported in source

    Hypoxic C2C12 myoblast cells
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Pretreatment of murine myoblast (C2C12) cells with octyl-D-carnosine or carnosine enhanced HIF-1α protein expression, VEGF mRNA levels and VEGF release under hypoxic conditions.
  12. 12LabIn vitro (cells)Mechanism

    In hypoxic C2C12 cells, carnosine pretreatment enhanced VEGF mRNA levels.

    In plain wordsIn cells under low oxygen, carnosine pretreatment increased VEGF mRNA levels.

    Outcome
    IncreaseVEGF mRNA
    Study

    mousen: not reported in source

    Hypoxic C2C12 myoblast cells
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Pretreatment of murine myoblast (C2C12) cells with octyl-D-carnosine or carnosine enhanced HIF-1α protein expression, VEGF mRNA levels and VEGF release under hypoxic conditions.
  13. 13LabIn vitro (cells)Mechanism

    In hypoxic C2C12 cells, carnosine pretreatment enhanced VEGF release.

    In plain wordsIn cells under low oxygen, carnosine pretreatment increased VEGF release.

    Outcome
    IncreaseVEGF release
    Study

    mousen: not reported in source

    Hypoxic C2C12 myoblast cells
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Pretreatment of murine myoblast (C2C12) cells with octyl-D-carnosine or carnosine enhanced HIF-1α protein expression, VEGF mRNA levels and VEGF release under hypoxic conditions.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    27 Oct 2026, 18:20 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:32 UTC

    First added · source update from Europe PMC

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