期刊
CARDIOVASCULAR DRUG REVIEWS
卷 25, 期 1, 页码 14-29出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1527-3466.2007.00002.x
关键词
Akt; AMPK; apoptosis; cell survival; H11 kinase; Hsp22; hypertrophy; ischemia; mTOR
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL072863, P01HL069020, R01HL093415] Funding Source: NIH RePORTER
- NHLBI NIH HHS [P01 HL069020, R01 HL072863, R01 HL093415] Funding Source: Medline
H11 kinase (H11K) is a small heat shock protein expressed predominantly in the heart and skeletal muscle, which plays a critical role in the maintenance of cardiac cell survival and in promoting cell growth through the activation of complementary signaling pathways. An overexpression of H11K was detected in various forms of heart disease, both in animal models and in patients, including acute and chronic ventricular dysfunction, and myocardial hypertrophy. Overexpression of H11K was reproduced in a cardiac-specific transgenic model, which led to significant progress in understanding the role and mechanism of action of the protein. Increased expression of H11K confers a cardioprotection that is equivalent to ischemic preconditioning; it promotes cardiac hypertrophy while maintaining contractile function. The overexpression of H11K is sufficient to activate most of the signaling pathways involved in cardiac cell growth and survival, including the phosphatidylinositol-3-kinase/Akt pathway, the AMP-dependent protein kinase, the PKC epsilon pathway of ischemic preconditioning, the nitric oxide pathway of delayed cardioprotection, and the mTOR pathway of cell growth. As a result, the survival response triggered by H11K in the heart includes antiapoptosis, cytoprotection, preconditioning, growth, and metabolic stimulation. In addition to activating signaling pathways, H11K promotes the subcellular translocation and crosstalk of intracellular messengers. This review discusses the biological function of H11K, its molecular mechanisms of action, and its potential therapeutic relevance. In particular, we discuss how preemptive conditioning of the heart by H11K might be beneficial for patients with ischemic heart disease who would be at risk of further irreversible cardiac damage.
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