Abrogation of mitochondrial transcription in smooth muscle cells impairs smooth muscle contractility and vascular tone

• Autorzy: Jawien J. , Bian Z. , Sheikine Y. , Olofsson P.S. , Pang Y. , Edholm T. , Dou Y. , Metzger D. , Hellstrom P.M. , Feil R. , Hansson G.K.
• Języki publikacji: EN

Abstrakty

EN

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.

Słowa kluczowe

EN

mitochondrion; blood vessel; contractile cell population; smooth muscle cell; hemodynamics; vascular tone; adenosine triphosphate; oxidative phosphorylation

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2008
• Tom: 59
• Numer: 2
• Opis fizyczny: p.239-252,fig.,ref.

Twórcy

autor

Jawien J.

• Jagiellonian University School of Medicine, 16 Grzegorzecka Str., 31-531 Krakow, Poland

autor

Bian Z.

autor

Sheikine Y.

autor

Olofsson P.S.

autor

Pang Y.

autor

Edholm T.

autor

Dou Y.

autor

Metzger D.

autor

Hellstrom P.M.

autor

Feil R.

autor

Hansson G.K.