Towards the understanding of the local hematopoietic bone marrow renin-angiotensin system

Haznedaroğlu, İbrahim C.; Öztürk, Mehmet Akif

doi:10.1016/s1357-2725(02)00278-9

Cited by 106 publications

(97 citation statements)

References 86 publications

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“…[4][5][6][7] The actions of Ang II are primarily mediated through AT 1 -and AT 2 -receptors, both of which are seven-transmembrane G-protein coupled receptors that share approximately 34% homology. 8,9 The cell signalling and physiological effects associated with AT 1 receptor activation are currently the most thoroughly defined. The necessity of AT 1 -receptors for normal progression of haematopoiesis was demonstrated by the development of panleukopeania and progenitor cell dysfunction in wildtype mice transplanted with AT 1 -receptor-deficient bone marrow.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells

Richmond

Tallant

Gallagher

et al. 2004

J Renin Angiotensin Aldosterone Syst

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Introduction Angiotensin II (Ang II) is recognised as a regulator of haematopoiesis, but its actions within the bone marrow are not fully understood. Support of haematopoiesis by bone marrow stromal cells (MSC) is dependent on factors that include arachidonic acid and macrophage colony stimulating factor (MCSF), both of which are increased by Ang II stimulation in other tissues. To further elucidate the mechanisms of Ang II-regulated haematopoiesis, we determined whether Ang II-stimulation alters arachidonic acid release and MCSF secretion from MSC. Methods Cynomolgus monkey MSC isolated from bone marrow aspirates and the human HS-5 stromal cell line were studied for Ang II-mediated arachidonic acid (AA) release, while secretion of MCSF in response to Ang II was studied in HS-5 cells. Cells were labelled overnight with 3H-AA and the release of 3H-AA was measured in culture medium following 20 minutes stimulation with Ang II, alone or in combination with the AT1- or AT 2-receptor antagonists, losartan and PD 123319, respectively. MCSF secretion into culture medium was measured using an enzyme immunoassay following 24 hours of treatment with Ang II alone or in combination with losartan or PD 123319. Phorbol-myristate-acetate, known to stimulate release of AA and MCSF, was used as a positive control in both experiments. Results In response to Ang II, release of 3H-AA from monkey and human MSC was increased (p<0.05) to 147±4% and 124±3% of control, respectively. The AT1- and AT2-receptor antagonists, losartan and PD 123319, individually reduced Ang II-stimulated 3H-AA release. In contrast, Ang II had no effect on secretion of MCSF from HS-5 cells. Conclusions These results provide mechanistic evidence for Ang II-mediated haematopoiesis through AA release that may, in part, explain Ang II-facilitated recovery of haematopoiesis in experimental myelosuppression and the anaemias associated with Ang II receptor blockade.

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Section: Introductionmentioning

confidence: 99%

Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells

Richmond

Tallant

Gallagher

et al. 2004

J Renin Angiotensin Aldosterone Syst

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“…The direct effects of angiotensin II also affect hematopoiesis [11][12][13]. The interaction between angiotensin II and AT1 receptor can lead to differentiation to the erythroid lineage, an effect that is blocked by losartan administration [1]. Losartan administration also blocks progenitor cell proliferation that is upregulated by angiotensin II [6], which supports the hypothesis that both angiotensin II and AT1 are involved in hematopoiesis, and that both ACE inhibitors and ARBs may inhibit this process.…”

Section: Discussionmentioning

confidence: 55%

“…ACE inhibitors suppress conversion of angiotensin I to angiotensin II, and ARBs block the interacttion of angiotensin II with the AT1 receptor, preventing activation of various cellular pathways. Recently, the RAS has been implicated in pathways beyond cardio vascular and renal regulation, including the modulation of hematopoiesis via local effects in the bone marrow [1].…”

Section: Introductionmentioning

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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“…14,15 Studies have also suggested that a local bone marrow angiotensin system exists and is inhibited by ACEIs and ARBs. 16,17 Angiotensin-converting enzyme inhibitors can cause anemia by a variety of other mechanisms apart from the decreased production of AT II. This is important because of AT II escape with chronic ACE inhibition through CAGE (chymostatin-sensitive angiotensin-II generating enzyme) and chymase pathways.…”

Section: Cross Talk Between Renin-angiotensin and Erythropoietin Systemsmentioning

confidence: 99%

Anemia in heart failure-A concise review

2005

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Summary: Heart failure affects 5 million persons in the United States, with 400,000 new cases occurring every year. Paradoxically, although advances in coronary angioplasty and effective drugs have increased survival post infarction, the myocardial damage and subsequent neurohormonal activation-induced remodeling causes significant morbidity years later in the form of heart failure. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) together with beta blockers modify the neurohormonal activation associated with heart failure and are key treatments for improving cardiac function and survival. Anemia is a significant risk factor predicting morbidity and mortality in heart failure. This article describes the various etiologies of anemia in heart failure. Of particular importance is the fact that recent stem cell studies have shown that the drugs acting on the renin-angiotensin system inhibit erythropoiesis in vivo and may cause anemia in patients with both normal renal function and end-stage renal disease (ESRD). The role of angiotensin-II as an erythropoietic growth factor and ACE in facilitating erythropoiesis is described in this article. Anemia has been shown to be a modifiable risk factor and its treatment correlates with improvement in clinical outcomes. Thus, anemia, its etiology (especially the contribution of ACEIs and ARBs), physiologic and prognostic impact, and treatment in the setting of heart failure are critical areas for investigation.

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Towards the understanding of the local hematopoietic bone marrow renin-angiotensin system

Cited by 106 publications

References 86 publications

Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells

Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells

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

Anemia in heart failure-A concise review

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