Platelet derived growth factor-A (Pdgf-a) gene transfer modulates scar composition and improves left ventricular function after infarction

被引：15

作者：

Rashid, N. Fairooj ^{[1
,2
]}

Clayton, E. Zoe ^{[1
,2
]}

Ogawa, Masahito ^{[1
,2
,7
]}

Perdomo, Jose ^{[5
,6
]}

Hume, D. Robert ^{[1
,2
]}

Kizana, Eddy ^{[1
,2
,3
,4
]}

Chong, J. H. James ^{[1
,2
,3
,4
]}

机构：

[1] Westmead Inst Med Res, Ctr Heart Res, 176 Hawkesbury Rd, Westmead, NSW 2145, Australia

[2] Univ Sydney, Sydney, NSW, Australia

[3] Westmead Hosp, Dept Cardiol, Westmead, NSW 2145, Australia

[4] Univ Sydney, Fac Med & Hlth, Sydney Med Sch, Sydney, NSW, Australia

[5] Univ New South Wales, Haematol Res Unit, Sydney, NSW, Australia

[6] Univ New South Wales, Sutherland Clin Sch, Sydney, NSW, Australia

[7] Natl Cerebral & Cardiovasc Ctr, Dept Regenerat Med & Tissue Engn, Osaka, Japan

来源：

INTERNATIONAL JOURNAL OF CARDIOLOGY | 2021年 / 341卷

基金：

英国医学研究理事会;

关键词：

PDGF-A; Gene therapy; Myocardial infarction; Angiogenesis; Scar; ADENOASSOCIATED VIRUS AAV; MYOCARDIAL-INFARCTION; CARDIAC FIBROSIS; PROGENITOR CELLS; FETAL; EXPRESSION; ANGIOGENESIS; REPAIR; BB;

D O I：

10.1016/j.ijcard.2021.07.021

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 adenoassociated 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 x 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.

引用

页码：24 / 30

页数：7

共 46 条

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