Angiotensin-(1-7) stimulates hematopoietic progenitor cells in vitro and in vivo

Heringer-Walther, Silvia; Eckert, K; Schumacher, Sarah-Mai; Uharek, Lutz; Wulf-Goldenberg, Annika; Gembardt, Florian; Fichtner, Iduna; Schultheiss, Heinz‐Peter; Rodgers, Kathy; Walther, Thomas

doi:10.3324/haematol.2008.000034

Cited by 69 publications

(56 citation statements)

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“…In recent years, investigations have demonstrated Ang-(1-7)-dependent effects on wound healing, 15 mechanisms involved in learning and memory, 16 cancer [17][18][19] and early progenitor cells. 20 Previously, we have shown that the receptor Mas is associated with Ang-(1-7)-stimulated intracellular signaling. 21 However, whether Ang II receptors are involved in Ang-(1-7)-stimulated effects is still under debate because some of the stimulated pathways are also affected by co-treatment with AT 1 blockers 22,23 or AT 2 blockers.…”

Section: Introductionmentioning

confidence: 97%

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

et al. 2012

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The renin-angiotensin system (RAS) has a vital role in regulating the cardiovascular system. The primary effector of the RAS is the octapeptide angiotensin (Ang) II, a potent regulator of blood pressure and water homeostasis. Ang II mediates its functions through the stimulation of two distinct receptors, AT 1 (two subtypes in rodents (AT 1a and AT 1b )) and AT 2 . It was shown that in addition to Ang II, shorter fragments of Ang are also biologically active. Ang-(1-7) came into focus because it opposes many of the detrimental effects of Ang II. However, it is still controversial whether Ang II receptors are involved in Ang-(1-7)-mediated signaling. To characterize the impacts of Ang II receptors on Ang-(1-7)-stimulated vascular relaxation, the effects of acute infusion of the three vasorelaxant compounds, that is, Ang-(1-7), bradykinin (BK) and acetylcholine (ACh), on heart rate (HR) and mean arterial pressure (MAP) were investigated in mice deficient for one, two or all three Ang II receptors. Ang-(1-7) and BK reduced MAP in wild-type, AT 1a /AT 1b -deficient and AT 2 -deficient mice. Although the change in absolute MAP values in the hypotensive triple knockouts (KO) could not be further reduced by both peptides, the percent change in MAP was comparable between the triple KO and wild-type mice. Both peptides did not alter the HR in all four genotypes. ACh significantly reduced absolute MAP values in all four genotypes with a similar percentage of reduction. In contrast to Ang-(1-7) and BK, ACh significantly reduced HR without genotypic differences. Our results generate proof that Ang-(1-7)-induced effects on MAP are mediated by a receptor that is independent of AT 1 and AT 2 .

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Section: Introductionmentioning

confidence: 97%

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

et al. 2012

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“…However, AcSDKP is likely not the sole effecttor of the RAS on hematopoiesis, as animal models demonstrate that infusions of angiotensin II can correct anemia in ACE-deficient mice [9]. Angiotensin II also upregulates erythropoietin levels and affects mitosis of erythroid progenitor cells and CD34+ stem cells [10]. Therefore, it is logical to hypothesize that using an ACEi to block conversion from angiotensin I to angiotensin II would affect mitotic activity of progenitor stem cells, potentially inhibiting hematopoiesis.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the Renin Angiotensin System during Autologous Stem Cell Transplant Does Not Impact Time to Engraftment

Kumar¹,

Carver²,

Frey³

2012

OJBD

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Background: The renin angiotensin system RAS modulates hematopoiesis via local effects in the bone marrow. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may adversely impact hematopoiesis and time to engraftment in patients undergoing stem cell transplant (SCT). Our study assesses whether the use of ACEi or ARBs delays time to engraftment in patients with multiple myeloma undergoing a melphalan based autologous SCT. Methods: A retrospective review of 58 patients who underwent autologous SCT with a melphalan 200 mg/m 2 conditioning regimen for multiple myeloma between January 1 and December 31, 2010 was performed. Results: Of 58 evaluable patients, 47 underwent autologous SCT without an ACEi or ARB (control group), and 11 patients were given ACEi or ARBs (treatment group). Mean time to neutrophil engraftment was 11.5 days in the control group, and 11.3 days in treatment group (p = 0.60). Mean time to platelet engraftment in control group was 13.5 days and 15.1 days in treatment group (p = 0.2). There was no statistically significant difference between groups in time to neutropenic fever and length of hospital stay. Conclusion: Our study demonstrates no significant difference in time to engraftment, incidence of neutropenic fever, or length of hospital stay between patients receiving ACEi or ARBS compared to control subjects. We demonstrate that use of low to moderate dose ACEi or ARB does not lead to prolonged time to engraftment and is safe to use in patients undergoing autologous SCT for multiple myeloma.

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“…Наиболее широко используемые стимуляторы гемопоэза(эритропоэтин, гранулоцитарныйколоние-стимулирующийфактор)действуютнаболеепоздние клетки-предшественникиистимулируютпролифера-циюидифференцировку1клеточнойлинии.Пептиды РАCявляютсямощнымистимуляторамипролифера-цииклеток-предшественников [16,26].Доклиничес-кие исследования ангиотензина 1-7 предполагают возможность увеличения множества линий ранних гемопоэтическихклеток-предшественников,культи-вированныхизКМипериферическойкровимышей. Этиисследованияпоказали,чтоинфузияангиотензи-на1-7послесублетальногооблученияилихимиотера-пииускорилавосстановлениегемопоэзасповышением мультилинейнойдифференцировкигемопоэтических клеток-предшественниковвКМиростчислалейко-цитовитромбоцитоввпериферическойкрови [24].…”

Section: заключениеunclassified

“…S.Heringer-Waltherисоавт.исследоваливлияние ангиотензина1-7напролиферациюin vitroиприжив-лениеin vivoчеловеческихклеток-предшественников вКМмышейNOD/SCID.Авторамибылоустановле-но,чтометаболитангиотензинаII,ангиотензин1-7, стимулируетпролиферациюCD34 + клетокпуповин-ной крови in vitro и что введение мононуклеарных пуповинныхклетокспоследующимдобавлениеман-гиотензина1-7улучшаетприживлениечеловеческих гемопоэтических клеток-предшественников в КМ умышей [25,26].…”

Section: Introductionunclassified

Renin-Angiotensin System in Regulation of Hematopoiesis

Канаева¹,

Galtseva²,

Nakastoev³

et al. 2018

Onkogematologiâ

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Angiotensin-(1-7) stimulates hematopoietic progenitor cells in vitro and in vivo

Cited by 69 publications

References 10 publications

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

Inhibition of the Renin Angiotensin System during Autologous Stem Cell Transplant Does Not Impact Time to Engraftment

Renin-Angiotensin System in Regulation of Hematopoiesis

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