Senescent Impairment in Synergistic Cytokine Pathways That Provide Rapid Cardioprotection in the Rat Heart
| Autor: | Andrew Chin, Victoria L.T. Ballard, Inga Duignan, Jacquelyne M. Holm, Munira Xaymardan, Jay M. Edelberg, Jingang Zheng |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Vascular Endothelial Growth Factor A
Aging Receptor Platelet-Derived Growth Factor alpha Platelet-derived growth factor Myocardial Infarction Coronary Disease 030204 cardiovascular system & hematology platelet-derived growth factor Mice chemistry.chemical_compound 0302 clinical medicine Immunology and Allergy Cells Cultured Cardioprotection 0303 health sciences vascular endothelial growth factor Reverse Transcriptase Polymerase Chain Reaction angiopoietin apoptosis Drug Synergism Immunohistochemistry Receptor TIE-2 Vascular endothelial growth factor Vascular endothelial growth factor A cardiovascular system medicine.medical_specialty Cardiotonic Agents Immunology Biology Article Angiopoietin-2 Angiopoietin 03 medical and health sciences Internal medicine In Situ Nick-End Labeling medicine Animals DNA Primers 030304 developmental biology Myocardium Kinase insert domain receptor Vascular Endothelial Growth Factor Receptor-2 Rats Inbred F344 Rats Mice Inbred C57BL Transplantation Endocrinology Gene Expression Regulation chemistry Coronary occlusion |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20031639 |
| Popis: | Pretreatment of rodent hearts with platelet-derived growth factor (PDGF)–AB decreases myocardial injury after coronary occlusion. However, PDGF-AB cardioprotection is diminished in older animals, suggesting that downstream elements mediating and/or synergizing the actions of PDGF-AB may be limited in aging cardiac vasculature. In vitro PDGF-AB induced vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-2 expression in 4-mo-old rat cardiac endothelial cells, but not in 24-mo-old heart cells. In vivo injection of young hearts with PDGF-AB increased densities of microvessels staining for VEGF and its receptor, Flk-1, and Ang-2 and its receptor, Tie-2, as well as PDGF receptor (PDGFR)–α. In older hearts, PDGF-AB–mediated induction was primarily limited to PDGFR-α. Studies in a murine cardiac transplantation model demonstrated that synergist interactions of PDGF-AB plus VEGF plus Ang-2 (PVA) provided an immediate restoration of senescent cardiac vascular function. Moreover, PVA injection in young rat hearts, but not PDGF-AB alone or other cytokine combinations, at the time of coronary occlusion suppressed acute myocardial cell death by >50%. However, PVA also reduced the extent of myocardial infarction with an age-associated cardioprotective benefit (4-mo-old with 45% reduction vs. 24-mo-old with 24%; P < 0.05). These studies showed that synergistic cytokine pathways augmenting the actions of PDGF-AB are limited in older hearts, suggesting that strategies based on these interactions may provide age-dependent clinical cardiovascular benefit. |
| Databáze: | OpenAIRE |
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