Article

A role for the renin-angiotensin system in hematopoiesis

Haematologica (Impact Factor: 5.87). 07/2009; 94(6):745-7. DOI: 10.3324/haematol.2009.006965
Source: PubMed
Download full-text

Full-text

Available from: Tea Soon Park, Aug 07, 2015
0 Followers
 · 
147 Views
  • Source
    • "Although it is controversial, the existence of a local bone marrow (BM) RAS has been demonstrated in rats [9]. Because the BM is a highly organized, complex organ, that is, the principal hematopoietic tissue in adults, locally BM-formed Ang II may be an autocrine or paracrine peptide that affects physiological and pathological hematopoiesis [10]. Studies have demonstrated that Ang II plays a role in oxidative stress development in the spontaneously hypertensive rat [11] and in the renovascular hypertensive rat [12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been proposed that the nonhemodynamic effects of angiotensin II are important for the damage observed in the two-kidney, one-clip (2K1C) renovascular hypertension model. Much evidence confirms that angiotensin II is directly involved in NAD(P)H oxidase activation and consequent superoxide anion production, which can damage DNA. The current study was performed to examine the effects of angiotensin-II-dependent hypertension in bone marrow mononuclear cells (BM-MNC); dihydroethidium staining was used to assess reactive oxygen species (ROS) production, and the comet assay was used to assess DNA fragmentation in 2K1C hypertensive mice 14 days after renal artery clipping. In this study we demonstrated that 2K1C hypertensive mice have an elevated lymphocyte count, while undifferentiated BM-MNC counts were diminished. 2K1C mice also showed an augmented ROS production and marked BM-MNC DNA fragmentation. In conclusion, endogenous renin angiotensin system activation-induced arterial hypertension is characterized by excessive ROS production in BM-MNC, which might cause marked DNA damage.
    02/2013; 2013:305202. DOI:10.1155/2013/305202
  • [Show abstract] [Hide abstract]
    ABSTRACT: For cancers to develop, sustain and spread, the appropriation of key homeostatic physiological systems that influence cell growth, migration and death, as well as inflammation and the expansion of vascular networks are required. There is accumulating molecular and in vivo evidence to indicate that the expression and actions of the renin-angiotensin system (RAS) influence malignancy and also predict that RAS inhibitors, which are currently used to treat hypertension and cardiovascular disease, might augment cancer therapies. To appreciate this potential hegemony of the RAS in cancer, an expanded comprehension of the cellular actions of this system is needed, as well as a greater focus on translational and in vivo research.
    Nature Reviews Cancer 11/2010; 10(11):745-59. DOI:10.1038/nrc2945 · 29.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inhibition of angiotensin-converting enzyme (ACE) induces anemia in humans and mice, but it is unclear whether ACE is involved in other aspects of hematopoiesis. Here, we systemically evaluated ACE-knockout (KO) mice and found myelopoietic abnormalities characterized by increased bone marrow myeloblasts and myelocytes, as well as extramedullary myelopoiesis. Peritoneal macrophages from ACE-KO mice were deficient in the production of effector molecules, such as tumor necrosis factor-α, interleukin-12p40, and CD86 when stimulated with lipopolysaccharide and interferon-γ. ACE-KO mice were more susceptible to Staphylococcus aureus infection. Further studies using total or fractionated bone marrows revealed that ACE regulates myeloid proliferation, differentiation, and functional maturation via angiotensin II and substance P and through the angiotensin II receptor type 1 and substance P neurokinin 1 receptors. Angiotensin II was correlated with CCAAT-enhancer-binding protein-α up-regulation during myelopoiesis. Angiotensin II supplementation of ACE-KO mice rescued macrophage functional maturation. These results demonstrate a previous unrecognized significant role for ACE in myelopoiesis and imply new perspectives for manipulating myeloid cell expansion and maturation.
    The FASEB Journal 12/2010; 25(4):1145-55. DOI:10.1096/fj.10-169433 · 5.48 Impact Factor
Show more