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Prolongation and enhancement of the anti-apoptotic effects of PTD-Hsp27 fusion proteins using an injectable thermo-reversible gel in a rat myocardial infarction model

 Young-Wook Won  ;  Jang-Kyung Kim  ;  Min-Ji Cha  ;  Ki-Chul Hwang  ;  Donghoon Choi  ;  Yong-Hee Kim 
 JOURNAL OF CONTROLLED RELEASE, Vol.144(2) : 181-189, 2010 
Journal Title
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Animals ; Apoptosis/drug effects* ; Apoptosis/genetics ; Apoptosis/physiology ; Cell Death/drug effects ; Cell Death/genetics ; Gels/pharmacology ; HSP27 Heat-Shock Proteins/pharmacology* ; Half-Life ; Injections ; Male ; Myocardial Infarction/drug therapy* ; Myocardial Infarction/genetics ; Myocardium/metabolism ; Protein Structure, Tertiary/genetics ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/pharmacology
Heat shock protein 27-protein transduction domain fusion protein ; Thermo-reversible gel ; Anti-apoptosis ; Ischemia-reperfusion ; Myocardial infarction
Ischemic heart disease has emerged as a leading cause of death worldwide. Conventional surgery-based therapy for this disease, especially myocardial infarction, requires additional pharmaceutical agents using heart's endogenous protective mechanism to suppress the progress and recurrence of the disease. Heat shock protein 27 (Hsp27) has been considered to be a potentially therapeutic protein for the treatment of ischemic heart disease due to its anti-apoptotic and protective effects on cardiomyocytes under stressful conditions. Despite the potency of Hsp27, low transduction efficiency, protein instability, and a short half-life in the body have limited its in vivo applications. Protein transduction domains (PTD) were recombinantly fused with Hsp27 to enhance transduction efficiency. Although the intracellular delivery of the PTD-Hsp27 fusion proteins was significantly enhanced compared with Hsp27, the instability and short half-life of the PTD-Hsp27 fusion proteins still need to be improved for in vivo applications. Injectable thermo-reversible gel system was developed and found to be effective in stabilizing and retarding the release of the PTD-Hsp27 fusion proteins both in vitro and in vivo. PTD-Hsp27-loaded thermo-reversible gels were locally administered to the heart muscle in a ligation/reperfused rat myocardial infarction model and the long-term therapeutic efficacy was observed by measuring the inhibition of apoptosis and the area of fibrosis.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Cha, Min Ji(차민지)
Choi, Dong Hoon(최동훈) ORCID logo https://orcid.org/0000-0002-2009-9760
Hwang, Ki Chul(황기철)
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