Effects of the Antioxidative  -Blocker Celiprolol on Endothelial Progenitor Cells in Hypertensive Rats

Yao, En-Hui; Fukuda, Noboru; Matsumoto, Tarô; Katakawa, Mayumi; Yamamoto, Chii; Han, Ying; Ueno, Takayoshi; Kobayashi, Noboru; Matsumoto, Koichí

doi:10.1038/ajh.2008.233

Cited by 44 publications

(28 citation statements)

References 26 publications

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“…This observation is consistent with previous reports that bone marrow-derived progenitor cells, specifically EPCs, from hypertensive humans and animals are functionally impaired and are reduced in number (9,28). Reduced efficacy of autologous donor cells is a major obstacle for ultimate clinical application of cell-based therapy.…”

Section: Discussionsupporting

confidence: 92%

Bone marrow mononuclear cells induce beneficial remodeling and reduce diastolic dysfunction in the left ventricle of hypertensive SS/MCWi rats

Parker

Didier

Karcher

et al. 2012

Physiological Genomics

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Little is known about the effectiveness of BMMNC therapy in hypertensive heart disease. In the current study, we show that delivery of BMMNCs from hypertension protected SS-13 BN /MCWi donor rats, but not BMMNC from hypertension susceptible SS/MCWi donor rats, resulted in 57.2 and 83.4% reductions in perivascular and interstitial fibrosis, respectively, as well as a 60% increase in capillary-to-myocyte count in the left ventricles (LV) of hypertensive SS/MCWi recipients. These histological changes were associated with improvements in LV compliance and relaxation (103 and 46.4% improvements, respectively). Furthermore, improved diastolic function in hypertensive SS/MCWi rats receiving SS-13 BN /MCWi derived BMMNCs was associated with lower clinical indicators of heart failure, including reductions in end diastolic pressure (65%) and serum brain natriuretic peptide levels (49.9%) with no improvements observed in rats receiving SS/MCWi BMMNCs. SS/MCWi rats had a lower percentage of endothelial progenitor cells in their bone marrow relative to SS-13 BN /MCWi rats. These results suggest that administration of BMMNCs can prevent or reverse pathological remodeling in hypertensive heart disease, which contributes to ameliorating diastolic dysfunction and associated symptomology. Furthermore, the health and hypertension susceptibility of the BMMNC donor are important factors influencing therapeutic efficacy, possibly via differences in the cellular composition of bone marrow.

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Section: Discussionsupporting

confidence: 92%

Bone marrow mononuclear cells induce beneficial remodeling and reduce diastolic dysfunction in the left ventricle of hypertensive SS/MCWi rats

Parker

Didier

Karcher

et al. 2012

Physiological Genomics

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“…Thus, AT 1 R signaling is involved in stem= progenitor cell dysfunctions leading to hypertensive vascular injury. In line with these findings, antioxidative b 1 -adrenoceptor blocker celiprolol decreases oxidative stress in hypertension and improves EPC numbers and function (232). Aldosterone, which increases oxidative stress, inhibits the formation of EPCs, at least in part by attenuating VEGFR2 expression and subsequent Akt signaling (136).…”

Section: Nadph Oxidase and Dysfunction Of Stem=progenitor Cells In Pasupporting

confidence: 62%

Novel Role of NADPH Oxidase in Angiogenesis and Stem/Progenitor Cell Function

Ushio‐Fukai

Urao

2009

Antioxidants & Redox Signaling

130

115

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Neovascularization is involved in normal development and wound repair as well as ischemic heart disease and peripheral artery disease. Both angiogenesis and vasculogenesis [de novo new vessel formation through mobilization of stem=progenitor cells from bone marrow (BM) and their homing to the ischemic sites] contribute to the formation of new blood vessels after tissue ischemia. Angiogenesis is dependent on cell proliferation, migration, and capillary tube formation in endothelial cells (ECs). Stem=progenitor cells have been used for cellbased therapy to promote revascularization after peripheral or myocardial ischemia. Excess amounts of reactive oxygen species (ROS) are involved in senescence and apoptosis of ECs and stem=progenitor cells, causing defective neovascularization. ROS at low levels function as signaling molecules to mediate cell proliferation, migration, differentiation, and gene expression. NADPH oxidase is one of the major sources of ROS in ECs and stem=progenitor cells, and is activated by various growth factors, cytokines, hypoxia, and ischemia. ROS derived from NADPH oxidase play an important role in redox signaling linked to angiogenesis ECs, as well as stem=progenitor cell mobilization, homing, and differentiation, thereby promoting neovascularization. Understanding these mechanisms may provide insight into NADPH oxidase and its mediators as potential therapeutic targets for ischemic heart and limb disease.

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“…As CFU-En numbers may be influenced by comorbidities and medications, we have studied effects of these variables in both patient cohorts. Twenty-two of 35 hematological patients had at least one cardiovascular or metabolical comorbidity (ischemic heart disease, hypertension, diabetes mellitus or hyperlipidemia), and 10 patients were taking at least one medication known to influence numbers of CFU-En or EPC in PB ( [9,[26][27][28][29][30][31], Table 3). Patients with one or more comorbidities had indeed lower numbers of CFU-En than patients with no comorbidity (median, 1.85 vs. 6.75 CFUEn/ml blood, p ¼ 0.03), but even in hematological patients without comorbidities, numbers of CFU-En colonies were significantly lower than in healthy controls ( p ¼ 0.002).…”

Section: Resultsmentioning

confidence: 99%

Endothelial cells (EC) and endothelial precursor cells (EPC) kinetics in hematological patients undergoing chemotherapy or autologous stem cell transplantation (ASCT)

Kideryová

Pytlík

Benešová

et al. 2010

Hematological Oncology

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Our objective was to study the kinetics of circulating endothelial cells (EC) and endothelial precursor cells (EPC) in hematological patients during chemotherapy and autologous stem cell transplantion (ASCT). Eighteen newly diagnosed patients and 17 patients undergoing ASCT were studied and compared to healthy controls. ECs were evaluated as CD146+CD31+Lin- cells, while EPCs were evaluated as CD34+CD133+Lin-, or CD34+VEGFR2+Lin- cells, or CFU-En colony forming units. Numbers of these cells were evaluated before and after treatment, and, in patients treated with ASCT, during mobilization of hematopoietic progenitors. Both newly diagnosed patients and patients before ASCT had significantly higher number of CD146+CD31+Lin- cells and significantly lower number of CFU-En colonies than healthy controls. These parameters did not return to normal for at least 3 months after chemotherapy or ASCT. Numbers of CFU-En did not correlate either with numbers of CD34+CD133+Lin- cells or with numbers of CD34+VEGFR2+Lin- cells but they did correlate with numbers of CD4+ lymphocytes and NK cells. In conclusion, we have found that hematological patients have higher number of EC and lower numbers of CFU-En than healthy controls and that these parameters do not return to normal after short-term follow-up. Furthermore, our observations support emerging data that CFU-En represent cell population different from flowcytometrically defined EC and endothelial precursors and that their development requires cooperation of monocytes and CD4+ lymphocytes. However, cells forming CFU-En express endothelial surface markers and can contribute to proper endothelial function by NO production.

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Effects of the Antioxidative -Blocker Celiprolol on Endothelial Progenitor Cells in Hypertensive Rats

Abstract: EPCs are impaired in SHRs in response to oxidative stress. Celiprolol decreases oxidative stress in hypertension in vivo and improves EPC numbers and function. It appears, therefore, that celiprolol may exert beneficial cardiovascular effects through its antioxidative properties.

Cited by 44 publications

References 26 publications

Bone marrow mononuclear cells induce beneficial remodeling and reduce diastolic dysfunction in the left ventricle of hypertensive SS/MCWi rats

Bone marrow mononuclear cells induce beneficial remodeling and reduce diastolic dysfunction in the left ventricle of hypertensive SS/MCWi rats

Novel Role of NADPH Oxidase in Angiogenesis and Stem/Progenitor Cell Function

Endothelial cells (EC) and endothelial precursor cells (EPC) kinetics in hematological patients undergoing chemotherapy or autologous stem cell transplantation (ASCT)

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