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.
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.
Won
Young-Wook
YW
Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, 17, Haengdang-dong, Seongdong-gu, Seoul, 133-791, Republic of Korea.
Kim
Jang-Kyung
JK
Cha
Min-Ji
MJ
Hwang
Ki-Chul
KC
Choi
Donghoon
D
Kim
Yong-Hee
YH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D005782:Gels / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins / Q000494:pharmacology*; D006207:Half-Life; D006360:Heat-Shock Proteins; D007267:Injections; D008297:Male; D018832:Molecular Chaperones; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics; D009206:Myocardium / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D005782:Gels; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins