Kathy Rodgers

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

This study demonstrates that the angiotensin II metabolite Ang-(1-7) stimulates the proliferation of hematopoietic progenitor cells and promotes their engraftment in a xenograft model, suggesting that the renin-angiotensin system is a regulator of blood cell formation. See related perspective article on page 745. Effects of angiotensin (Ang)-(1–7), an AngII metabolite, on bone marrow-derived hematopoietic cells were studied. We identified Ang-(1–7) to stimulate proliferation of human CD34+ and mononuclear cells in vitro. Under in vivo conditions, we monitored proliferation and differentiation of human cord blood mononuclear cells in NOD/SCID mice. Ang-(1–7) stimulated differentially human cells in bone marrow and accumulated them in the spleen. The number of HLA-I+ and CD34+ cells in the bone marrow was increased 42-fold and 600-fold, respectively. These results indicate a decisive impact of Ang-(1–7) on hematopoiesis and its promising therapeutic potential in diseases requiring progenitor stimulation.

Angiotensin-(1–7) administration benefits cardiac, renal and progenitor cell function in db/db mice

Diabetic patients are at an increased risk of cardiovascular disease, in part due to inflammation and oxidative stress. These two pathological mechanisms also affect other organs and cells including the kidneys and progenitor cells. Angiotensin‐(1–7) [Ang‐(1–7)] has previously been shown to counterbalance pathological effects of angiotensin II, including inflammation and oxidative stress. The aim of this study was to investigate the effects of short‐term (2 weeks) Ang‐(1–7) treatment on cardiovascular and renal function in a mouse model of type 2 diabetes (db/db).

Angiotensin-(1–7) Administration Reduces Oxidative Stress in Diabetic Bone Marrow

Diabetics have an increased risk of developing cardiovascular disease, in part due to oxidative stress, resulting in endothelial nitric oxide synthase (eNOS) dysfunction. Studies have demonstrated that angiotensin-(1-7) [Ang-(1-7)] can activate eNOS activity. Because the bone marrow is a primary source of a number of progenitors important in physiological homeostasis and healing, the goal of this study was to evaluate the in vivo effects of Ang-(1-7) treatment on oxidative stress and the ensuing nitrative stress in diabetic bone marrow and its potential pathways. BKS.Cg-Dock7(m) +/+ Lepr(db)/J mice and their heterozygous controls were administered Ang-(1-7) alone or combined with A-779, losartan, PD123,319, nitro-l-arginine methyl ester, or icatibant sc for 14 d. The bone marrow was then collected to measure nitric oxide levels, eNOS phosphorylation, and expression of nitric oxide synthase, superoxide dismutase, and p22-phox. Nitric oxide levels in the bone marrow were significantly decreased in diabetic mice, and Ang-(1-7) treatment was able to significantly increase these measures (P < 0.01). This effect was blocked by the coadministration of PD123,319, A-779, nitro-l-arginine methyl ester, and icatibant. In addition, Ang-(1-7) treatment reversed the paradoxical increase in eNOS and neuronal nitric oxide synthase expression and decreased the phosphorylation of eNOS at Thr495 seen in diabetic mice. Ang-(1-7) also reversed diabetes-induced production of reactive oxygen species by decreasing p22-phox expression and increasing superoxide dismutase 3 expression, leading to a significant reduction in 3-nitrotyrosine formation in diabetic bone marrow (P < 0.05). Our findings demonstrate that Ang-(1-7) administration decreases diabetes-induced oxidative stress in the bone marrow and modifies pathways involved in eNOS dysfunction.

Effects of the renin angiotensin system on vasculogenesis-related progenitor cells.

The current concept is that there are both cells that integrate into the vasculature, true endothelial progenitor cells (EPC), and cells with hematopoietic markers that support neovascularisation. As identification of the EPC is controversial and studies refer cells that might fall into either pools, we will use the term, vasculogenesis-related progenitor cells (VRPC), for this review. VRPC are considered to be an important target for the treatment of cardiovascular diseases (CVD). Angiotensin II is known to be an important player in neovascularisation and the modulation of renin angiotensin system (RAS) is one of the major pharmacotherapeutic strategies for the treatment of CVD. We will review the effects of different components of the RAS on such VRPC under physiological conditions and in CVD. The reviewed research strongly supports a critical role of the RAS in vasculogenesis and vascular regeneration. Therefore, pharmacological intervention on the components of the RAS does not only target directly end-organ remodelling and blood pressure but also influence tissue healing and/or regeneration by influencing specific progenitor cells. Thus, the interrogation of RAS effects on VRPC will be important in the optimisation of RAS intervention or regenerative therapy.

Basal levels of CD34 positive cells in peripheral blood differ between individuals and are stable for 18 months

Detection of basal levels of CD34 progenitor cells is a rare event analysis enumerating cells down to 1 cell/μl. A reproducible analytic approach was used in three independent clinical trials in which multiple sequential assays were obtained from the same individual.

Enhanced follicle regulatory protein levels accompany reinitiation of ovulatory function after parturition

OBJECTIVES We examined the changes in follicle regulatory protein, estrone-3-glucuronide, pregnanediol-3-glucuronide, and luteinizing hormone levels in first-morning urine samples from postpartum, fully breast-feeding women to characterize the reemergence of these urinary hormones after pregnancy ovarian quiescence and early postpartum period and to determine whether follicle regulatory protein could be used prospectively to predict the return of fertility. STUDY DESIGN Twenty-five hundred urine samples collected from six postpartum women were evaluated. Daily urine samples collected from normally cycling women were used to establish normal urinary hormone and hormone metabolite cyclicity. Luteinizing hormone, estrone-3-glucuronide, and pregnanediol-3-glucuronide levels were measured by radioimmunoassay. Follicle regulatory protein level was assayed with a double-antibody enzyme-linked immunosorbent assay. RESULTS Although follicle regulatory protein levels were found to be very low or undetectable in early postpartum urine, they began to rise with episodes of estrone-3-glucuronide and pregnanediol-3-glucuronide secretion. A chi 2 analysis suggests that increasing urinary follicle regulatory protein levels are most closely associated with the luteal phase of the first menstrual cycles in postpartum women. CONCLUSIONS These results suggest that follicle regulatory protein is of little value in predicting either the onset of renewed ovarian activity or the fertile period.