What question did this study set out to answer?

To determine whether sarco(endo)plasmic reticulum Ca2+-ATPase isoform 3 (SERCA3) regulates vascular smooth muscle tone and endothelial cell Ca2+ signaling.

November 1, 1997Journal of Biological ChemistryOpen Access

Defective Endothelium-dependent Relaxation of Vascular Smooth Muscle and Endothelial Cell Ca2+ Signaling in Mice Lacking Sarco(endo)plasmic Reticulum Ca2+-ATPase Isoform 3

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Population

Mice with a null mutation in the SERCA3 gene and wild-type mice, including aortic ring preparations and…

Comparison

SERCA3 gene knockout (null mutation) vs Wild-type mice

Design

Preclinical

Authors

LLLynne H. LiuLaboratory of Molecular Genetics RPRichard J. PaulUniversity of Cincinnati RSRoy L. SutliffNational Institutes of Health

Discussion

Member takes

Implication

Implicates SERCA3 in endothelial NO-mediated relaxation; leaves open translation to human vascular disease.

Key Points

To determine whether sarco(endo)plasmic reticulum Ca2+-ATPase isoform 3 (SERCA3) regulates vascular smooth muscle tone and endothelial cell Ca2+ signaling.
Generated homozygous SERCA3 null mutant mice using gene-targeting techniques.
Measured isometric contractile and relaxation responses of isolated aortic rings exposed to phenylephrine, KCl, a nitric oxide donor, and acetylcholine.
Conducted Ca2+ imaging in cultured aortic endothelial cells to evaluate acetylcholine-evoked intracellular Ca2+ transients and store refilling.
Acetylcholine-induced endothelium-dependent aortic relaxation was significantly blunted in homozygous null mutants compared to wild-type mice (35.4 +/- 7.3% vs. 61.3 +/- 5.6%).
Contraction force generation in response to phenylephrine or KCl, as well as relaxation induced by a direct nitric oxide donor, did not differ between null mutants and wild-type controls.
Cultured SERCA3-deficient endothelial cells exhibited markedly diminished acetylcholine-induced Ca2+ transients and severely impaired replenishment of intracellular Ca2+ stores.

Structured PICO

Population

Mice with a null mutation in the SERCA3 gene (homozygous mutant mice) and wild-type mice, including aortic ring preparations and cultured aortic endothelial cells.

Intervention

SERCA3 gene knockout (null mutation)

Comparator

Wild-type mice

Outcome

Acetylcholine-induced endothelium-dependent relaxation of aortas and intracellular Ca2+ signaling in cultured aortic endothelial cellssurrogate

SERCA3 plays a critical role in endothelial cell Ca2+ signaling events involved in nitric oxide-mediated relaxation of vascular smooth muscle.

Cite This Study

Liu et al. (1997) studied this question.

synapsesocial.com/papers/6a83cd0b21c6da9699fe1673 https://doi.org/10.1074/jbc.272.48.30538

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Defective Endothelium-dependent Relaxation of Vascular Smooth Muscle and Endothelial Cell Ca2+ Signaling in Mice Lacking Sarco(endo)plasmic Reticulum Ca2+-ATPase Isoform 3

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Defective Endothelium-dependent Relaxation of Vascular Smooth Muscle and Endothelial Cell Ca2+ Signaling in Mice Lacking Sarco(endo)plasmic Reticulum Ca2+-ATPase Isoform 3

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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