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;
‡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: firstname.lastname@example.org). Reprints: Sugata Hazra, PhD, Indian Institute of Technology Kanpur, Kanpur 208016, India (e-mail: email@example.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