What question did this study set out to answer?

To determine the molecular mechanism of acute statin-stimulated endothelial nitric oxide synthase (eNOS) activation and whether it is coupled to altered site-specific phosphorylation.

April 20, 2004AJP Heart and Circulatory Physiology

Acute activation and phosphorylation of endothelial nitric oxide synthase by HMG-CoA reductase inhibitors

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Population

Bovine aortic endothelial cells (BAECs), passages 2-6

Comparison

Lovastatin or pravastatin for 0 to 30 minutes vs Control/inhibitors

Design

Preclinical

Follow-up

30 minutes

Authors

MHM. Brennan HarrisUniversity of North Carolina at Chapel Hill MBMichele A. BlackstoneAugusta University SSSarika G. SoodAugusta University

Discussion

Member takes

Implication

Acute statin effects on eNOS remain preclinical; leaves open translation to human vascular outcomes.

Key Points

To determine the molecular mechanism of acute statin-stimulated endothelial nitric oxide synthase (eNOS) activation and whether it is coupled to altered site-specific phosphorylation.
Treated bovine aortic endothelial cells (passages 2–6) with lovastatin or pravastatin across 0 to 30 minutes.
Evaluated site-specific eNOS phosphorylation (Ser-1179, Ser-635, Ser-617, Thr-497, Ser-116) via Western blot using phosphospecific antibodies and kinase inhibitors (wortmannin, KT-5720).
Quantified nitric oxide release via cGMP accumulation in the presence of L-NAME, wortmannin, KT-5720, and mevalonate.
Statin stimulation elevated eNOS phosphorylation at Ser-1179 and Ser-617 via PI3-kinase/Akt and at Ser-635 via PKA.
Statin exposure caused a transient 4-fold increase in nitric oxide release that was attenuated by L-NAME, wortmannin, and KT-5720, but not by mevalonate.

Structured PICO

Population

Bovine aortic endothelial cells (BAECs), passages 2-6

Intervention

Lovastatin or pravastatin for 0 to 30 minutes

Comparator

Control/inhibitors (wortmannin, KT-5720, mevalonate)

Outcome

eNOS phosphorylation (Ser-1179, Ser-635, Ser-617, Thr-497, Ser-116) and NO release (measured by cGMP accumulation)surrogate

Statins acutely activate eNOS and increase NO release via phosphorylation at specific serine residues through PKA and Akt pathways, independent of HMG-CoA reductase inhibition.

Cite This Study

Harris et al. (2004) studied this question.

synapsesocial.com/papers/6a7ac735bdf697b3de02c711 https://doi.org/10.1152/ajpheart.00214.2004

Topics

Statin therapy

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Acute activation and phosphorylation of endothelial nitric oxide synthase by HMG-CoA reductase inhibitors

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Acute activation and phosphorylation of endothelial nitric oxide synthase by HMG-CoA reductase inhibitors

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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Topics

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