title: Endothelial progenitor cell differentiation and senescence in an angiotensin II-infusion rat model.
abstract: The ability of endothelial progenitor cells (EPCs) to participate in endothelial repair is impaired by angiotensin II (Ang II) and other atherogenic factors. Therefore, we investigated the effects of Ang II on the differentiation and senescence of EPCs derived from bone marrow (BM-EPCs) in an Ang II-infusion rat model. Wistar rats (n=40) were infused with Ang II or vehicle, either alone or in combination with an Ang II type 1 receptor (AT(1)R) blocker (valsartan). Bone marrow cells were obtained from the tibias and femurs. Rats of the Ang II treatment group had a significantly lower number of differentiated, adherent BM-EPCs than those of the non-treated control group. Addition of valsartan restored the level of attached, differentiated BM-EPCs to the level in the non-treated controls. The number of senescent BM-EPCs, as assessed by acidic beta-galactosidase staining, was significantly greater in the Ang II-alone group than the control group, and addition of valsartan dramatically delayed the senescence of BM-EPCs in the Ang II-alone group. A polymerase chain reaction (PCR)-ELISA-based assay revealed that telomerase activity was significantly lower in BM-EPCs from the Ang II-alone group than in those from the control group, and addition of valsartan significantly augmented this activity. An MTS assay revealed that Ang II treatment significantly decreased the functional activity in BM-EPCs, and this effect was significantly reversed by valsartan. In conclusion, Ang II decreased the differentiation and accelerated the senescence of BM-EPCs via AT(1)R.
authors.affiliation: Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Imanishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019098:Telomerase / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D013777:Tetrazoles; D014665:Vasodilator Agents; D000804:Angiotensin II; D006830:Hydralazine; D000068756:Valsartan; D019098:Telomerase; D014633:Valine