Linear unstable angiotensins stimulate hematopoiesis. Here we address: (1) Is cyclic angiotensin-(1-7) myeloprotective in mice? (2) Is cyclic angiotensin-(1-7) stable in rat? (3) Does LP2, a cyclic angiotensin-(1-7) with an N-terminal d-lysine, exert myeloprotective action in tumor-bearing mice?

Materials and Methods

Cyclic angiotensin-(1-7)'s capacity to restore levels of blood platelets and white blood cells was studied in gemcitabine-treated mice. The stability of cyclic angiotensin-(1-7) in rat was measured in blood samples taken after injection or infusion. The capacity of LP2 to restore total bone marrow cell levels in mice after treatment with 5-fluoruracil was measured. In addition, the capacity of LP2 to counter anemia in tumor-bearing mice treated with erlotinib was measured.

Results

Cyclic angiotensin-(1-7) dose-dependently restored blood platelet levels in gemcitabine-treated mice, whereas its capacity to restore levels of white blood cells was less. In vivo aminoterminal breakdown of cyclic angiotensin-(1-7) yielded cyclic angiotensin-(2-7) and cyclic angiotensin-(3-7). LP2 significantly (p < .0001 at 100 μg/kg/day) restored bone marrow cell counts in mice after treatment with 5-fluoruracil. LP2 also significantly (p < .05) countered anemia in tumor-bearing mice treated with erlotinib.

Conclusions

LP2 exerts myeloprotective action with perspectives for continuation of its clinical development.

CONFLICT OF INTEREST STATEMENT

PN, KER and RF have no conflict of interest. GNM is owner of Lanthio Holding.

Open Research

DATA AVAILABILITY STATEMENT

The data from this study are readily available after reasonable request to the corresponding author.

Supporting Information

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Volume110, Issue5

May 2023

Pages 534-539

LP2, a stable lanthipeptide derived from cAng-(1-7), exerts myeloprotective action in mice

Abstract

Objectives

Materials and Methods

Results

Conclusions

CONFLICT OF INTEREST STATEMENT

Open Research

DATA AVAILABILITY STATEMENT

Supporting Information

REFERENCES

References

Information

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LP2, a stable lanthipeptide derived from cAng-(1-7), exerts myeloprotective action in mice

Abstract

Objectives

Materials and Methods

Results

Conclusions

CONFLICT OF INTEREST STATEMENT

Open Research

DATA AVAILABILITY STATEMENT

Supporting Information

REFERENCES

References

Related

Information