| Abrogation of mitochondrial transcription in smooth muscle cells impairs smooth muscle contractility and vascular tone. | |
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MedLine Citation:
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PMID: 18622043 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Smooth muscle cells (SMC) constitute the major contractile cell population of blood vessels and inner organs. SMC contraction depends on energy provided by adenosine triphosphate (ATP) catabolism, which can be generated through oxidative phosphorylation in mitochondria or by anaerobic glycolysis. Mitochondrial activity may also modulate smooth muscle tone by biotransformation of vasoactive mediators. Here, we study the role of mitochondrial DNA gene expression for vascular function in vivo. METHODS: Since loss of functional mitochondria in SMC may not be compatible with normal development, we generated mice with inducible SMC-specific abrogation of the mitochondrial transcription factor A (Tfam). Deletion of this gene leads to dysfunctional mitochondria and prevents aerobic ATP production in affected cells. RESULTS: Invasive blood pressure monitoring in live animals demonstrated that SMC specific Tfam deletion results in lower blood pressure and a defective blood-pressure response to stress, changes that were not compensated by increased heart rate. The contractility to agonists was reduced in arterial and gastric fundus strips from Tfam-deficient mice. Endothelium-dependent relaxation of arterial strips in response to ACh was also blunted. CONCLUSION: Our data show that mitochondrial function is needed for normal gastric contraction, vascular tone, and maintenance of normal blood pressure. |
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Authors:
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J Jawien; Z Bian; Y Sheikine; P S Olofsson; Y Pang; T Edholm; Y Dou; D Metzger; P M Hellström; R Feil; G K Hansson |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society Volume: 59 ISSN: 1899-1505 ISO Abbreviation: J. Physiol. Pharmacol. Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-07-14 Completed Date: 2008-11-25 Revised Date: 2009-01-05 |
Medline Journal Info:
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Nlm Unique ID: 9114501 Medline TA: J Physiol Pharmacol Country: Poland |
Other Details:
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Languages: eng Pagination: 239-52 Citation Subset: IM |
Affiliation:
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Department of Medicine; Karolinska Institute, Stockholm, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Male Mice Mice, Transgenic Mitochondria / genetics, physiology* Muscle Contraction / genetics, physiology* Muscle, Smooth, Vascular / cytology, physiology* Myocytes, Smooth Muscle / cytology, physiology* Transcription, Genetic / genetics, physiology* Vasoconstriction / genetics, physiology* |
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