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Translation of PDGF cardioprotective pathways
Jay M Edelberg1, Dongqing Cai, Munira Xaymardan
1Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA. jme2002@med.cornell.edu
Insights
Aging impairs heart vascular function, increasing heart disease risk. Restoring platelet-derived growth factor (PDGF) pathways and using stem cells can improve cardiac angiogenesis and offer new therapies for aging cardiovascular disease.
Area of Science:
- Cardiovascular Science
- Aging Research
- Regenerative Medicine
Background:
- Vascular function declines with age, contributing to ischemic heart disease.
- Impaired platelet-derived growth factor (PDGF) pathways in aged cardiac cells are a key factor.
- This dysfunction increases morbidity and mortality in older individuals.
Purpose of the Study:
- To investigate methods for restoring vascular function in the aging heart.
- To explore the role of PDGF pathways and stem cells in cardiac angiogenesis.
- To identify therapeutic strategies for age-related cardiovascular disease.
Main Methods:
- Examined PDGF-mediated pathways in senescent cardiac microvascular endothelial cells.
- Utilized intramyocardial injection of growth factors for transient rescue.
- Employed transplantation of young bone marrow-derived stem cells for long-term reconstitution in mice.
Main Results:
- Restoration of PDGF pathways transiently improved senescent cardiac angiogenesis.
- Stem cell transplantation promoted long-term recovery of cardiac angiogenic function.
- Enhanced PDGF pathways demonstrated cardioprotective effects, reducing myocardial injury.
Conclusions:
- Targeting PDGF pathways and stem cell homing offers potential for novel therapies.
- Strategies to enhance cardiac angiogenesis can protect against myocardial infarction in aging.
- These findings provide a foundation for preventing and treating age-related cardiovascular disease.
Abstract:
Vascular function in the aging heart is impaired and may underlie the increased morbidity and mortality associated with ischemic heart disease in older individuals. This vascular dysfunction is due, in part, to impairment of platelet derived growth factor (PDGF)-mediated pathways in senescent cardiac microvascular endothelial cells. Restoration of these pathways by intramyocardial injection of growth factor transiently rescues senescent cardiac angiogenesis. Longer-term reconstitution can be achieved experimentally by transplantation of young bone marrow-derived stem cells to promote senescent cardiac angiogenic function in the murine host. Moreover, enhancement of PDGF pathways is cardioprotective, markedly reducing the extent of myocardial injury following coronary occlusion. The clinical translation of these findings for treatment of ischemic heart diseases must overcome the limitation of the proatherosclerotic actions of PDGF, as well as the generation of autologous stem/precursor cell approaches, for the aging cardiovascular system. Strategies targeting growth factor and/or stem-cell homing to gene products downstream of PDGF in the cardiac microvasculature may provide positive feedback loops to enhance cardiac angiogenesis and protection from myocardial infarction and may offer a foundation for developing novel therapies for the prevention and treatment of cardiovascular disease associated with aging.