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Genetic Ablation and Guanylyl Cyclase/Natriuretic Peptide Receptor-A: Impact on the Pathophysiology of Cardiovascular

Kailash N Pandey1

  • 1Department of Physiology, Tulane University Health Sciences Center, School of Medicine, New Orleans, LA 70112, USA. kpandey@tulane.edu.

International Journal of Molecular Sciences
|August 17, 2019
PubMed

Insights

Gene targeting in mice reveals natriuretic peptide receptor 1 (NPR1) gene variations influence hypertension and cardiovascular disease risk. Both gene disruption and duplication impact these conditions, offering insights into genetic susceptibility and resistance.

Area of Science:

  • Cardiovascular Science
  • Genetics
  • Nephrology

Background:

  • Genetic mutations affecting natriuretic peptides (NPs) and their receptors (NPRs) are crucial for understanding hypertension, kidney disease, and cardiovascular dysfunction.
  • Studies involving complete gene disruption and tissue-specific gene ablation in mice have advanced knowledge of hypertension and cardiovascular disorders.
  • Oligogenic inheritance, involving interactions among a few alleles, may explain genetic susceptibility to hypertension, renal insufficiency, and congestive heart failure.

Purpose of the Study:

  • To review the phenotypes of natriuretic peptide receptor 1 (Npr1) gene disruption and duplication in mice.
  • To emphasize the roles of Npr1 gene targeting in mouse models concerning hypertension and cardiovascular events.
  • To elucidate how Npr1 gene manipulation contributes to understanding the dose-dependent regulation of hypertension and cardiovascular events by NPs and NPRs.

Main Methods:

  • Analysis of mouse models with targeted gene mutations, including complete gene disruption and tissue-specific gene ablation.
  • Examination of mouse models with Npr1 gene duplication.
  • Focus on mouse models carrying Npr1 gene knockout and/or gene duplication for studying hypertension and cardiovascular events.

Main Results:

  • Gene knockouts of Npr1 increase the risk of hypertension, kidney disorders, and cardiovascular dysfunction.
  • Gene duplications of Npr1 have identified mutations that protect against high blood pressure and cardiovascular events.
  • These findings suggest that specific alleles can confer resistance to hypertension and heart disease.

Conclusions:

  • Npr1 gene targeting in mice provides critical insights into the pathogenesis of hypertension and cardiovascular diseases.
  • Both loss-of-function (disruption) and gain-of-function (duplication) of Npr1 impact cardiovascular health and blood pressure regulation.
  • Understanding Npr1 gene variants in mice contributes to knowledge of NP and NPR roles in dose-dependent regulation of cardiovascular events.
Keywords:
atrial natriuretic peptidecongestive heart failuregene-duplicationgene-knockoutguanylyl cyclase/natriuretic peptide receptor-Ahypertension

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