Overexpression of Nitric Oxide Synthase Restores Circulating Angiogenic Cell Function in Patients With Coronary Artery Disease: Implications for Autologous Cell Therapy for Myocardial Infarction

Autor: Xiaoyin Wang, Stephen M. Black, Brian T. Clifford, Monika Varga, Emmy Luu, Wenhui Gong, Ronak Derakhshandeh, Olivia M. Danforth, Qiumei Chen, Kirstin Aschbacher, Lejla Medzikovic, Matthew L. Springer, Ruslan Rafikov, Songtao An, Jeffrey R. Fineman, Sergey V. Suchkov, Christian Heiss, Dmitry Kostyushev, Daniel J. Haddad, Yan Zhang, Yerem Yeghiazarians
Přispěvatelé: Graduate School
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Time Factors
Genetic enhancement
Myocardial Infarction
Mice
SCID
Coronary Artery Disease
030204 cardiovascular system & hematology
Cardiorespiratory Medicine and Haematology
Cardiovascular
Vascular Medicine
Coronary artery disease
chemistry.chemical_compound
Mice
0302 clinical medicine
Transduction
Genetic
Enos
Cell Movement
Myocardial infarction
Cells
Cultured
Original Research
Cultured
biology
nitric oxide synthase
Middle Aged
gene therapy
3. Good health
Nitric oxide synthase
Vascular endothelial growth factor
Phenotype
Heart Disease
Endothelium/Vascular Type/Nitric Oxide
Cardiology
cardiovascular system
RNA Interference
Female
Cardiology and Cardiovascular Medicine
Signal Transduction
Biotechnology
Cardiac function curve
Adult
medicine.medical_specialty
Nitric Oxide Synthase Type III
Cells
Neovascularization
Physiologic
SCID
Nitric Oxide
Transfection
Nitric oxide
03 medical and health sciences
Transduction
Genetic
Clinical Research
Internal medicine
medicine
Animals
Humans
Regeneration
cardiovascular diseases
Physiologic
Neovascularization
Heart Disease - Coronary Heart Disease
Aged
endothelial progenitor cells
business.industry
Animal
Prevention
nutritional and metabolic diseases
Recovery of Function
biology.organism_classification
medicine.disease
Atherosclerosis
Coculture Techniques
Disease Models
Animal
030104 developmental biology
Peripheral Vascular Disease
Animal Models of Human Disease
chemistry
circulating angiogenic cells
Case-Control Studies
Immunology
Disease Models
biology.protein
business
Stem Cell Transplantation
Zdroj: Journal of the American Heart Association, vol 5, iss 1
Journal of the American Heart Association, 5(1). Wiley-Blackwell
Chen, Q; Varga, M; Wang, X; Haddad, DJ; An, S; Medzikovic, L; et al.(2016). Overexpression of Nitric Oxide Synthase Restores Circulating Angiogenic Cell Function in Patients With Coronary Artery Disease: Implications for Autologous Cell Therapy for Myocardial Infarction. JOURNAL OF THE AMERICAN HEART ASSOCIATION, 5(1). doi: 10.1161/JAHA.115.002257. UCSF: Retrieved from: http://www.escholarship.org/uc/item/453697nx
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
Popis: Background Circulating angiogenic cells ( CAC s) are peripheral blood cells whose functional capacity inversely correlates with cardiovascular risk and that have therapeutic benefits in animal models of cardiovascular disease. However, donor age and disease state influence the efficacy of autologous cell therapy. We sought to determine whether age or coronary artery disease ( CAD ) impairs the therapeutic potential of CAC s for myocardial infarction ( MI ) and whether the use of ex vivo gene therapy to overexpress endothelial nitric oxide ( NO ) synthase ( eNOS ) overcomes these defects. Methods and Results We recruited 40 volunteers varying by sex, age (< or ≥45 years), and CAD and subjected their CAC s to well‐established functional tests. Age and CAD were associated with reduced CAC intrinsic migration (but not specific response to vascular endothelial growth factor, adherence of CAC s to endothelial tubes, eNOS mRNA and protein levels, and NO production. To determine how CAC function influences therapeutic potential, we injected the 2 most functional and the 2 least functional CAC isolates into mouse hearts post MI . The high‐function isolates substantially improved cardiac function, whereas the low‐function isolates led to cardiac function only slightly better than vehicle control. Transduction of the worst isolate with eNOS cDNA adenovirus increased NO production, migration, and cardiac function of post‐ MI mice implanted with the CAC s. Transduction of the best isolate with eNOS small interfering RNA adenovirus reduced all of these capabilities. Conclusions Age and CAD impair multiple functions of CAC s and limit therapeutic potential for the treatment of MI . eNOS gene therapy in CAC s from older donors or those with CAD has the potential to improve autologous cell therapy outcomes.
Databáze: OpenAIRE
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