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Glypican 1 and syndecan 1 differently regulate noradrenergic hypertension development: Focus on IP3R and calcium

Simone R Potje1, Ayman Isbatan2, Rita C Tostes3

  • 1Department of Anesthesiology, College of Medicine Tucson, University of Arizona, USA; Department of Anesthesiology, College of Medicine, University of Illinois at Chicago, USA; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.

Pharmacological Research
|August 19, 2021
PubMed

Insights

Glypican 1 and syndecan 1 regulate blood pressure. Glypican 1 deficiency protects against hypertension by altering calcium signaling, suggesting it as a therapeutic target.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Hypertension Research

Background:

  • Vascular dysfunction is critical in hypertension development.
  • Heparan sulfate proteoglycans (HSPG) influence nitric oxide (NO) and calcium signaling, vital for vascular function.
  • The roles of HSPG in NO/calcium signaling, vascular dysfunction, and blood pressure regulation remain unclear.

Purpose of the Study:

  • To investigate if HSPGs, specifically syndecan 1 and glypican 1, control systemic blood pressure.
  • To elucidate the mechanisms by which glypican 1 and syndecan 1 regulate vascular tone.
  • To determine their contribution to the development of noradrenergic hypertension.

Main Methods:

  • Systemic arterial blood pressure assessment in knockout mouse models (Sdc1-/- and Gpc1-/-).
  • Evaluation of calcium-dependent vasoconstriction and expression of calcium-sensitive proteins.
  • Analysis of inositol trisphosphate receptor (IP3R) activity and endoplasmic reticulum calcium storage.

Main Results:

  • Both Sdc1-/- and Gpc1-/- mice exhibited decreased systolic blood pressure, notably in Gpc1-/-.
  • Gpc1-/- mice were protected from norepinephrine-induced hypertension.
  • This protection correlated with impaired calcium-dependent vasoconstriction, altered SERCA and calmodulin expression, reduced IP3R activity, and increased ER calcium storage in Gpc1-/- mice.

Conclusions:

  • Glypican 1 acts as a trigger for noradrenergic hypertension via IP3R and calcium signaling pathways.
  • Glypican 1 represents a potential therapeutic target for resistant hypertension.
  • Targeting Glypican 1 may offer new treatment strategies for conditions with elevated norepinephrine.
Abstract

Keywords:
Acetylcholine (Pubmed CID:187)Caffeine (Pubmed CID:2519)CalciumCalcium dichloride (Pubmed CID: 5284359)Glypican 1HypertensionIP(3)RNifedipine (Pubmed CID: 4485)NorepinephrineNorepinephrine bitartrate (Pubmed CID: 297812)Phenylephrine (Pubmed CID: 6041)Potassium Chloride (Pubmed CID: 4873)Sodium Nitroprusside (Pubmed CID: 11953895)Syndecan 1

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