Effects of the antioxidative β-blocker celiprolol on endothelial progenitor cells in hypertensive rats

被引：38

作者：

Yao, En-Hui ^{[1
]}

Fukuda, Noboru ^{[1
,2
]}

Matsumoto, Taro ^{[3
]}

Katakawa, Mayumi ^{[1
]}

Yamamoto, Chii ^{[2
]}

Han, Ying ^{[1
]}

Ueno, Takahiro ^{[1
]}

Kobayashi, Naohiko ^{[4
]}

Matsumoto, Koichi ^{[1
]}

机构：

[1] Nihon Univ, Sch Med, Dept Med, Div Nephrol Hypertens & Endocrinol, Tokyo, Japan

[2] Nihon Univ, Adv Res Inst Sci & Humanities, Tokyo, Japan

[3] Nihon Univ, Sch Med, Dept Adv Med, Div Cell Regenerat & Transplantat, Tokyo, Japan

[4] Dokkyo Univ, Sch Med, Dept Cardiovasc Med, Tochigi, Japan

来源：

AMERICAN JOURNAL OF HYPERTENSION | 2008年 / 21卷 / 09期

关键词：

D O I：

10.1038/ajh.2008.233

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

BACKGROUND Endothelial progenitor cells (EPCs) derived from bone marrow migrate to areas of endothelial damage and repair them. EPC function is impaired by oxidative stress. We examined the effects of an antioxidative beta(1)-adrenoceptor blocker on the number and function of EPCs in hypertensive rats. METHODS Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were fed diets loaded with high salt. The SHRs were treated with celiprolol or atenolol for 2 weeks. Peripheral blood mononuclear cells (MNCs) were separated, subjected to flow cytometric analysis to determine the number of circulating EPCs, and cultured to quantify EPC colony formation. EPC migration was evaluated in migration assay chambers. EPC senescence was evaluated using beta-galactosiclase assay. Oxidative stress of EPCs was evaluated using thiobarbituric acid-reactive substance (TBARS) assay. The expression of nicotinamine adenine dinucleotide phosphate (NAD(P)H) oxidase component mRNAs in the renal cortex, aorta, and heart were evaluated by real-time PCR. RESULTS The number, colony formation, and migration of EPCs in SHRs were significantly lower than those in WKY rats. TBARS scores in EPCs from SHRs were significantly higher than those from WKY rats. Celiprolol increased the number of circulating EPCs and stimulated EPC colony formation and migration, while decreasing EPC senescence. Celiprolol inhibited oxidation in EPCs from SHRs, and decreased the expression of NAD(P)H oxidase component mRNAs in the renal cortex, aorta, and heart. CONCLUSION 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.

引用

页码：1062 / 1068

页数：7

共 28 条

[1] Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J].

Asahara, T ;

Masuda, H ;

Takahashi, T ;

Kalka, C ;

Pastore, C ;

Silver, M ;

Kearne, M ;

Magner, M ;

Isner, JM .

CIRCULATION RESEARCH, 1999, 85 (03) :221-228

[2] VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells [J].

Asahara, T ;

Takahashi, T ;

Masuda, H ;

Kalka, C ;

Chen, DH ;

Iwaguro, H ;

Inai, Y ;

Silver, M ;

Isner, JM .

EMBO JOURNAL, 1999, 18 (14) :3964-3972

[3] Effects of establishing cell cultures and cell culture conditions on the proliferative life span of human fibroblasts isolated from different tissues and donors of different ages [J].

Balin, AK ;

Fisher, AJ ;

Anzelone, M ;

Leong, I ;

Allen, RG .

EXPERIMENTAL CELL RESEARCH, 2002, 274 (02) :275-287

[4] Antioxidative stress-associated genes in circulating progenitor cells: evidence for enhanced resistance against oxidative stress [J].

Dernbach, E ;

Urbich, C ;

Brandes, RP ;

Hofmann, WK ;

Zeiher, AM ;

Dimmeler, S .

BLOOD, 2004, 104 (12) :3591-3597

[5] Production of angiotensin II by homogeneous cultures of vascular smooth muscle cells from spontaneously hypertensive rats [J].

Fukuda, N ;

Satoh, C ;

Hu, WY ;

Soma, M ;

Kubo, A ;

Kishioka, H ;

Watanabe, Y ;

Izumi, Y ;

Kanmatsuse, K .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (05) :1210-1217

[6] Circulating endothelial progenitor cells, vascular function, and cardiovascular risk [J].

Hill, JM ;

Zalos, G ;

Halcox, JPJ ;

Schenke, WH ;

Waclawiw, MA ;

Quyyumi, AA ;

Finkel, T .

NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (07) :593-600

[7] Estrogen reduces angiotensin II-induced acceleration of senescence in endothelial progenitor cells [J].

Imanishi, T ;

Hano, T ;

Nishio, I .

HYPERTENSION RESEARCH, 2005, 28 (03) :263-271

[8] Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction [J].

Imanishi, T ;

Hano, T ;

Sawamura, T ;

Nishio, I .

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2004, 31 (07) :407-413

[9] A mouse model of angiotensin II slow pressor response: Role of oxidative stress [J].

Kawada, N ;

Imai, E ;

Karber, A ;

Welch, WJ ;

Wilcox, CS .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2002, 13 (12) :2860-2868

[10] Celiprolol activates eNOS through the PI3K-Akt pathway and inhibits VCAM-1 via NF-κB induced by oxidative stress [J].

Kobayashi, N ;

Mita, S ;

Yoshida, K ;

Honda, T ;

Kobayashi, T ;

Hara, K ;

Nakano, S ;

Tsubokou, Y ;

Matsuoka, H .

HYPERTENSION, 2003, 42 (05) :1004-1013

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