Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
September 4, 2008AJP Cell PhysiologyOpen Access

MAP kinase/phosphatase pathway mediates the regulation of ACE2 by angiotensin peptides

View Full Paper
Ask AI
Bookmark
Share

Population

Hypertensive rats and rat aortic vascular smooth muscle cells (VSMCs)

Design

Preclinical

Authors

PGPatricia E. GallagherWake Forest UniversityCFCarlos M. FerrarioPreventive CardiologyETE. Ann TallantWake Forest University

Discussion

Loading...

Member takes

Implication

Hypothesis-generating in rat VSMCs; leaves open relevance to human vascular disease or RAS therapies.

Key Points

  • To determine the molecular signaling pathways through which angiotensin II and angiotensin-(1-7) regulate angiotensin-converting enzyme 2 (ACE2) expression and activity.
  • Treated cultured rat aortic vascular smooth muscle cells (VSMCs) with angiotensin II alone and in combination with angiotensin-(1-7).
  • Evaluated ACE2 mRNA and activity, along with ERK1/ERK2 activation, in the presence of selective peptide receptor antagonists and kinase/phosphatase inhibitors.
  • Angiotensin II downregulated ACE2 mRNA and enzymatic activity in VSMCs while increasing ERK1/ERK2 MAP kinase phosphorylation.
  • Angiotensin-(1-7) co-treatment and the MAP kinase kinase inhibitor PD98059 each prevented the angiotensin II-induced decline in ACE2 mRNA.
  • Inhibition of tyrosine or serine-threonine phosphatases blocked the protective effect of angiotensin-(1-7), indicating that angiotensin-(1-7) preserves ACE2 via MAP kinase phosphatase activation.

Structured PICO

P
Population
Hypertensive rats and rat aortic vascular smooth muscle cells (VSMCs)
I
Intervention
Angiotensin II (ANG II), Angiotensin-(1-7) [ANG-(1-7)], and various inhibitors (olmesartan, PD98059, sodium vanadate, okadaic acid)
O
Outcome
ACE2 mRNA and protein levels, and ACE2 activitysurrogate

The MAP kinase-phosphatase pathway is a primary molecular mechanism for regulating ACE2 to maintain the balance between ANG II and ANG-(1-7).

Cite This Study

Gallagher et al. (2008) studied this question.

synapsesocial.com/papers/6a797bbd756812e39589167ahttps://doi.org/10.1152/ajpcell.00145.2008
View Full Paper
Ask AI
Bookmark
Share

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Intracellular mechanisms involved in vascular remodelling of resistance arteries in hypertension: role of angiotensin II2005 · 238 citations
  2. 2Upregulation of Angiotensin-Converting Enzyme 2 After Myocardial Infarction by Blockade of Angiotensin II Receptors2004 · 575 citations
  3. 3Angiotensin II AT1 receptors regulate ACE2 and angiotensin-(1–7) expression in the aorta of spontaneously hypertensive rats2005 · 205 citations
  4. 4Molecular Mechanisms of Inhibition of Vascular Growth by Angiotensin-(1-7)2003 · 169 citations
  5. 5Injections of angiotensin‐converting enzyme 2 inhibitor MLN4760 into nucleus tractus solitarii reduce baroreceptor reflex sensitivity for heart rate control in rats2008 · 77 citations