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

Abstract

AbstractObjectivesLinear 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 MethodsCyclic 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.ResultsCyclic 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.ConclusionsLP2 exerts myeloprotective action with perspectives for continuation of its clinical development.