Platelet derived growth factor-A (Pdgf-a) gene transfer modulates scar composition and improves left ventricular function after myocardial infarction.
- Resource Type
- Article
- Authors
- Rashid, Fairooj N.; Clayton, Zoë E.; Ogawa, Masahito; Perdomo, Jose; Hume, Robert D; Kizana, Eddy; Chong, James J.H.
- Source
- International Journal of Cardiology. Oct2021, Vol. 341, p24-30. 7p.
- Subject
- *GENETIC transformation
*PLATELET-derived growth factor
*MYOCARDIAL infarction
*LYSYL oxidase
*HEART failure
*WESTERN immunoblotting
*CAPILLARY electrophoresis
- Language
- ISSN
- 0167-5273
Background : Novel therapies that can limit or reverse damage caused by myocardial infarction (MI) could ease the increasing burden of heart failure. In this regard Platelet Derived Growth Factor (PDGF) has been previously shown to contribute to cardiac repair after MI. Here, we use a rodent model of MI and recombinant adeno-associated virus 9 (rAAV9)-mediated gene transfer to overexpress Pdgf-a in the injured heart and assess its therapeutic potential. Methods and results : Sprague Dawley rats underwent temporary occlusion of the left anterior descending coronary artery, followed immediately by systemic delivery of 1 × 10^11 vector genomes of either rAAV9 Pdgf-a or rAAV9 Empty vector (control). At day 28 post-MI echocardiography showed significantly improved left ventricular (LV) function (fractional shortening) after rAAV9 Pdgf-a (0.394 ± 0.019%) treatment vs control (0.304 ± 0.018%). Immunohistochemical analysis demonstrated significantly increased capillary and arteriolar density in the infarct border zone of rAAV9 Pdgf-a treated hearts together with a significant reduction in infarct scar size (rAAV9 Pdgf-a 6.09 ± 0.94% vs Empty 12.45 ± 0.92%). Western blot and qPCR analyses confirmed overexpression of PDGF-A and showed upregulation of smooth muscle alpha actin (Acta2) , collagen type III alpha 1 (Col3a1) and lysyl oxidase (Lox) genes in rAAV9 Pdgf-a treated infarcts. Conclusion : Overexpression of Pdgf-a in the post-MI heart can modulate scar composition and improve LV function. Our study highlights the potential of rAAV gene transfer of Pdgf-a as a cardio-reparative therapy. • Recombinant AAV9 Pdgf-a gene therapy upregulates PDGF-A in the rat heart. • Pdgf-a gene therapy led to improved left ventricular function post myocardial infarction. • PDGF-A upregulation increased neovascularization in the border zone and Collagen type III alpha 1 in the scar. • This study highlights post-infarct scar modulation as a target for cardiac reparative therapies. [ABSTRACT FROM AUTHOR]