Prothymosin α Gene Transfer Modulates Myocardial Remodeling after Ischemia-Reperfusion Injury

Ai Li Shiau, Shih Yuan Fang, Chih Hsin Hsu, Meng Hsuan Chiu, Chen Fuh Lam, Chao Liang Wu, Jun Neng Roan

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Prothymosin α(ProT), a polypeptide, attenuates inflammation and inhibits transforming growth factor (TGF)-β signaling in pulmonary tissues. We investigated the potential role of ProT in myocardial ischemiareperfusion (MyoIR) injury using ProT cDNA transfer. Methods: Serum ProT levels were investigated in cardiogenic shock patients with MyoIR (n = 9). In addition, the myocardium of Sprague-Dawley rats (n = 52) was subjected to 25 min of ischemia followed by an injection of adenoviral vectors (2 x 109 plaque-forming units) carrying ProT or the luciferase gene, 10 min before reperfusion. Echocardiography, serum ProT, and biochemical analyses of organ functions were performed before euthanasia, 14 days after treatment. Immunohistochemistry and immunoblotting of the myocardial tissue were also performed. Results: Serum ProT levels were transiently elevated in the rats and patients early after MyoIR, which was reduced to baseline levels in control rats and patients. ProT gene transfer persistently mobilized ProT serum levels, reduced dilatation, attenuated fibrotic changes, and preserved the left ventricular ejection fraction after MyoIR. Tissue thrombospondin-1 level was abundant, and matrix metalloproteinase-2, collagen I, and collagen IV levels were decreased in the treatment group. While TGF-β protein level remained stable, ProT transduction mobilized Smad7, which counteracted TGF-β. ProT reduced tissue microRNA-223 expression, inhibited the associated interleukin-1β, and preserved RAS p21 protein activator 1 protein abundance. Conclusions: An increase in transient serum ProT levels could be a protective response in the acute stage of MyoIR. ProT gene transfer further preserved ventricular morphology and function through anti-inflammatory and antifibrotic effects in the subacute stage after injury.

Original languageEnglish
Pages (from-to)187-200
Number of pages14
JournalActa Cardiologica Sinica
Volume38
Issue number2
DOIs
Publication statusPublished - 2022 Mar

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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