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Beneficial Effects of Angiotensin-(1–7) on CD34+ Cells From Patients With Heart Failure

Cole-Jeffrey, Colleen T. PhD*; Pepine, Carl J. MD; Katovich, Michael J. PhD; Grant, Maria B. MD§; Raizada, Mohan K. PhD*; Hazra, Sugata PhD*

Journal of Cardiovascular Pharmacology: March 2018 - Volume 71 - Issue 3 - p 155–159
doi: 10.1097/FJC.0000000000000556
Original Article
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Abstract: The dysfunctional nature of CD34+ cells from patients with heart failure (HF) may make them unsuitable for autologous stem-cell therapy. In view of evidence that the vasoprotective axis of the renin–angiotensin system (RAS) improves CD34+ cell functions, we hypothesized that CD34+ cells from patients with HF will be dysfunctional and that angiotensin-(1–7) [Ang-(1–7)] would improve their function. Peripheral blood was collected from New York Heart Association class II-IV patients with HF (n = 31) and reference subjects (n = 16). CD34+ cell numbers from patients with HF were reduced by 47% (P < 0.05) and also displayed 76% reduction in migratory capacity and 56% (P < 0.05) lower production of nitric oxide. These alterations were associated with increases in RAS genes angiotensin-converting enzyme and AT2R (595%, P < 0.05) mRNA levels and 80% and 85% decreases in angiotensin-converting enzyme 2 and Mas mRNA levels, respectively. Treatment with Ang-(1–7) enhanced CD34+ cell function through increased migratory potential and nitric oxide production, and reduced reactive oxygen species generation. These data show that HF CD34+ cells are dysfunctional, and Ang-(1–7) improves their functions. This suggests that activation of the vasoprotective axis of the RAS may hold therapeutic potential for autologous stem-cell therapy in patients with HF.

Departments of *Physiology and Functional Genomics;

Medicine; and

Pharmacodynamics, University of Florida, Gainesville, FL; and

§Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, AL.

Reprints: Mohan K. Raizada, PhD, Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610-0267 (e-mail: mraizada@ufl.edu). Reprints: Sugata Hazra, PhD, Indian Institute of Technology Kanpur, Kanpur 208016, India (e-mail: sugata.hazra@gmail.com).

Supported by a grant from the National Heart, Lung, and Blood Institute (NHLBI) 5RO1HL056921-21 (awarded to M. K. Raizada and M. J. Katovich) and a predoctoral grant from American Heart Association: 14PRE18620024 (awarded to C. T. Cole-Jeffrey). C. J. Pepine is supported by the NHLBI Cardiovascular Cell Therapy Network (CCTRN) UM 1 HL087318 and the UF Regional Clincal Center CCTRN Training Core Supplement under UM 1 HL087366, the Gatorade Trust through funds distributed by the UF, Department of Medicine, NIH NCATS UF Clinical and Translational Science UL1TR001427, and PCORnet-OneFlorida Clincal Research Consortium.

Funding for this work was received from the National Institutes of Health (NIH).

Received August 23, 2017

Accepted October 03, 2017

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