Document Detail

Hypertension impairs myocardin function - a novel mechanism facilitating arterial remodeling.
MedLine Citation:
PMID:  22843699     Owner:  NLM     Status:  Publisher    
AIMS: Hypertension evokes detrimental changes in the arterial vessel wall which facilitate stiffening and thus leads to a further rise in mean blood pressure eventually causing heart failure. The underlying pathophysiological remodeling process is elicited by an increase in wall stress (WS) and strictly dependent on the activation of vascular smooth muscle cells (SMC). However, it remains unclear as to why these cells fail to maintain their contractile and quiescent phenotype in a hypertensive environment.Methods and ResultsIn this context, we reveal that the knockdown of myocardin - a pivotal transcriptional determinant of the contractile SMC phenotype - is sufficient to induce SMC proliferation. In line with this observation, immunofluorescence analyses of the media of remodeling arteries from hypertensive mice demonstrate a significant decrease in the abundance of myocardin and an increase in SMC proliferation. Subsequent analyses of isolated perfused mouse arteries and human cultured SMCs exposed to cyclic stretch, i.e. mimicking one component of WS, suggest that this biomechanical force facilitates serine phosphorylation of myocardin. Furthermore, this biomechanical stimulus promotes irapid translocation of myocardin from the nucleus to the cytoplasm, inhibits its mRNA expression and causes proteasomal degradation of the cytoplasmatic protein. CONCLUSIONS: Collectively, these findings suggest that hypertension negates the activity of myocardin in SMCs on multiple levels hence eliminating a crucial determinant of SMC quiescence. This mechanism may control the initial switch from the contractile towards the synthetic SMC phenotype during hypertension and may offer an interesting novel concept to prevent cardiovascular disease.
Larissa Pfisterer; Anja Feldner; Markus Hecker; Thomas Korff
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-26
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, Germany.
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