Induction of intracellular heat-shock protein 72 prevents the development of vascular smooth muscle cell calcification
| Autor: | Tzongshi Lu, Yun-Chun Yang, Szu-Yu Yiao, Daniel Zehnder, Guerman Molostvov, Kenneth Lim, Li-Li Hsiao |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Serum Response Factor medicine.medical_specialty Vascular smooth muscle Physiology Myocytes Smooth Muscle Core Binding Factor Alpha 1 Subunit HSP72 Heat-Shock Proteins Coronary Artery Disease Biology Transfection Muscle Smooth Vascular Pathogenesis Young Adult Organ Culture Techniques Physiology (medical) Heat shock protein medicine.artery Internal medicine medicine Humans Myocyte RNA Messenger Renal Insufficiency Chronic Vascular Calcification Cells Cultured Aged Aged 80 and over Aorta Nuclear Proteins Middle Aged medicine.disease Up-Regulation Phenotype Endocrinology Case-Control Studies Trans-Activators Female Quercetin RNA Interference Signal transduction Cardiology and Cardiovascular Medicine Heat-Shock Response Intracellular Signal Transduction Calcification |
| Zdroj: | Cardiovascular Research. 96:524-532 |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvs278 |
| Popis: | Aims Vascular calcification (VC) is a significant contributor to cardiovascular mortality in patients with chronic kidney disease (CKD) and coronary artery disease (CAD). Osteo/chondrocytic transformation and simultaneous dedifferentiation of smooth muscle cells (SMCs) are important in the pathogenesis of VC. Heat-shock protein 72 (HSP72) is a cardioprotective inducible heat-shock protein that functions as a molecular chaperone. However, its role in the development of accelerated vascular dysfunction and calcification is largely unexplored. Methods and results We describe for the first time marked reduction in HSP72 expression in arteries from patients with CKD and CAD, compared with healthy controls, in vivo . Induction of HSP72 by heat-shock treatment (HST) significantly prevented the development of calcification of human aortic smooth muscle cells (HA-SMCs), in vitro. These anti-calcific effects were abolished following treatment with both quercetin, an HST inhibitor, and HSP72 siRNA knockdown . Induction of HSP72 suppressed Cbfa-1-dependent osteo/chondrocytic transformation and stabilized SMC contractile phenotype through the myocardin–serum response factor (SRF) pathway. Co-immunoprecipitation studies demonstrated physical association between SRF and HSP72. Furthermore, organ culture of arteries from CKD and CAD patients showed that these arteries retained their ability to induce HSP72 following HST, despite initially reduced expression. Conclusion Our study shows for the first time that intracellular HSP72 may function as a central regulator of molecular pathways involved in the development of VC. We suggest treatment strategies that up-regulate HSP72 as a new approach to inhibit VC. |
| Databáze: | OpenAIRE |
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