Analysis of CD45- [CD34+/KDR+] endothelial progenitor cells as juvenile protective factors in a rat model of ischemic-hemorrhagic stroke

• Published in: PloS one 2013-01, Vol.8 (1), p.e55222-e55222
• Main Authors: Decano, Julius L, Moran, Ann Marie, Giordano, Nicholas, Ruiz-Opazo, Nelson, Herrera, Victoria L M
• Format: Article
• Language: English
• Subjects: Age; Age factors; Aging; Aging - physiology; Analysis of Variance; Angiogenesis; Animals; Animals, Genetically Modified; Antigens, CD34 - metabolism; Biology; Bone marrow; Brain; Brain Ischemia - prevention & control; Cardiovascular disease; CD34 antigen; CD45 antigen; Cells (biology); Delay; Deoxyribonucleic acid; DNA; Endothelial Cells - metabolism; Endothelium; Female; Flow Cytometry; Gene expression; Genetic engineering; Health risks; Hemorrhage; Hypercholesterolemia; Hyperplasia; Hypertension; Infusion; Ischemia; Laboratory animals; Lesions; Leukocyte Common Antigens - metabolism; Magnetic Resonance Imaging; Maintenance; Male; Medicine; Pathogenesis; Physiology; Polymerase chain reaction; Protective Agents - metabolism; Protective Agents - pharmacology; Proteins; Rats; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Reversing; Risk acceptance; Risk factors; Rodents; Stem cells; Stem Cells - metabolism; Stroke; Stroke - prevention & control; Studies; Transgenic; Y chromosomes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0055222

Identification of juvenile protective factors (JPFs) which are altered with age and contribute to adult-onset diseases could identify novel pathways for reversing the effects of age, an accepted non-modifiable risk factor to adult-onset diseases. Since endothelial progenitor cells (EPCs) have been observed to be altered in stroke, hypertension and hypercholesterolemia, said EPCs are candidate JPFs for adult-onset stroke. A priori, if EPC aging plays a 'master-switch JPF-role' in stroke pathogenesis, juvenile EPC therapy alone should delay stroke-onset. Using a hypertensive, transgenic-hyperlipidemic rat model of spontaneous ischemic-hemorrhagic stroke, spTg25, we tested the hypothesis that freshly isolated juvenile EPCs are JPFs that can attenuate stroke progression and delay stroke onset. FACS analysis revealed that CD45- [CD34+/KDR+] EPCs decrease with progression to stroke in spTg25 rats, exhibit differential expression of the dual endodthelin-1/VEGFsp receptor (DEspR) and undergo differential DEspR-subtype specific changes in number and in vitro angiogenic tube-incorporation. In vivo EPC infusion of male, juvenile non-expanded cd45-[CD34+/KDR+] EPCs into female stroke-prone rats prior to stroke attenuated progression and delayed stroke onset (P