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Inducible cardiac‐specific RhoA‐expression protects against ischemia/reperfusion injury in mouse hearts
Author(s) -
Xiang Sunny Yang,
Ling Haiyun,
Del Re Dominic P.,
Purcell Nicole H,
Miyamoto Shigeki,
Matkovich Scott J.,
Dorn Gerald W.,
Brown Joan Heller
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.573.11
Subject(s) - rhoa , in vivo , rho associated protein kinase , small gtpase , microbiology and biotechnology , cardioprotection , kinase , reperfusion injury , protein kinase a , ischemia , chemistry , biology , medicine , signal transduction
The small GTPase RhoA has established roles in regulating cell growth and cytoskeletal dynamics but the role of RhoA in modulating cardiac hypertrophy and cell survival remains elusive. Inducible cardiac‐specific RhoA mice (RhoA DTG) expressing 2–5 fold increase in active RhoA showed no evident basal phenotype. Remarkably, isolated RhoA DTG hearts subjected to 45min global ischemia followed by 2h reperfusion displayed a 60% reduction in infarct size, decreased lactate dehydrogenase release and significantly improved post‐ischemic cardiac function compared to the wild‐type hearts. RhoA DTG hearts subjected to 30min coronary occlusion followed by 24h reperfusion in vivo showed even greater protection with infarct size reduced by more than 70%. The Rho Kinase (ROCK) inhibitor Y‐27632 enhanced rather than blocking the protection in RhoA DTGs, suggesting that ROCK is not downstream of RhoA‐mediated ischemia/reperfusion (I/R) protection. Activated protein kinase C epsilon and protein kinase D were significantly increased in the RhoA DTG heart, and their roles in the protective effect of RhoA are currently under investigation. In conclusion, inducible and cardiac‐specific RhoA‐expression provides strong protection against I/R injury in the mouse heart both ex vivo and in vivo, contrasting with the conventional notion that RhoA/ROCK signaling in the heart is maladaptive. (HL28143)