한빛사논문
- 조회1,737
University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center
Abstract
Kyung Hee Chang1,2, Ramesh C. Nayak2, Swarnava Roy2, Ajay Perumbeti1, Ashley M. Wellendorf2, Katie Y. Bezold2, Megan Pirman1, Sarah E. Hill1, Joseph Starnes2, Anastacia Loberg2, Xuan Zhou2, Tadashi Inagami3, Yi Zheng2, Punam Malik2 & Jose A. Cancelas1,2
1 Hoxworth Blood Center, University of Cincinnati College of Medicine, 3130 Highland Avenue, Cincinnati, Ohio 45267, USA. 2 Division of Experimental Hematology and Cell Biology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. 3 Department of Biochemistry, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, Tennessee 37232, USA.
Correspondence to: Punam Malik or Jose A Cancelas
Abstract
Patients with organ failure of vascular origin have increased circulating haematopoietic stem cells and progenitors (HSC/P). Plasma levels of angiotensin II (Ang-II), are commonly increased in vasculopathies. Hyperangiotensinemia results in activation of a very distinct Ang-II receptor set, Rho family GTPase members, and actin in bone marrow endothelial cells (BMEC) and HSC/P, which results in decreased membrane integrin activation in both BMEC and HSC/P, and in HSC/P de-adhesion and mobilization. The Ang-II effect can be reversed pharmacologically and genetically by inhibiting Ang-II production or signalling through BMEC AT2R, HSCP Ang-II receptor type 1 (AT1R)/AT2R or HSC/P RhoA, but not by interfering with other vascular tone mediators. Hyperangiotensinemia and high counts of circulating HSC/P seen in sickle cell disease (SCD) as a result of vascular damage, is significantly decreased by Ang-II inhibitors. Our data define for the first time the role of Ang-II HSC/P traffic regulation and redefine the haematopoietic consequences of anti-angiotensin therapy in SCD.
논문정보
- Research article
- 2015년 01월 (BRIC 등록일 2015-01-19)
- 국외 연구진
댓글 작성 로그인
팝업 닫기관련 링크
