Related Experiment Video

Updated: Jun 19, 2025

Assessing Endothelial Vasodilator Function with the Endo-PAT 2000
07:46

Assessing Endothelial Vasodilator Function with the Endo-PAT 2000

Published on: October 15, 2010

43.7K

Auto/Paracrine C-Type Natriuretic Peptide/Cyclic GMP Signaling Prevents Endothelial Dysfunction

Franziska Werner1, Takashi Naruke1, Lydia Sülzenbrück1

  • 1Institute of Physiology, University Würzburg, 97070 Würzburg, Germany.

International Journal of Molecular Sciences
|July 27, 2024
PubMed

Insights

Endothelial C-type natriuretic peptide (CNP) signaling protects female mice from cardiovascular disease. Deleting its receptor (GC-B) in endothelial cells worsened arterial stiffness, hypertension, and atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Endothelial Function
  • Molecular Signaling

Background:

  • Endothelial dysfunction is central to cardiovascular diseases.
  • C-type natriuretic peptide (CNP) is an endothelial hormone regulating vascular tone and barrier function.
  • The guanylyl cyclase-B (GC-B) receptor mediates CNP's effects and is expressed in endothelial cells.

Purpose of the Study:

  • To investigate the role of endothelial CNP/cGMP signaling in cardiovascular health and disease.
  • To characterize the impact of endothelial-selective GC-B deletion on vascular function and disease progression.
  • To explore potential sex-specific differences in CNP/GC-B signaling pathways.

Main Methods:

  • Generated mice with endothelial-selective deletion of the GC-B receptor (EC GC-B KO).
  • Assessed vascular structure, function, and inflammatory markers in EC GC-B KO mice.
  • Evaluated atherosclerosis development in EC GC-B KO and control mice on an Ldlr-deficient background.
  • Studied vascular regeneration capacity following hind-limb ischemia.

Main Results:

  • EC GC-B KO mice exhibited thicker, stiffer aortae and isolated systolic hypertension.
  • Increased expression of proinflammatory markers (E-selectin, VCAM-1) and impaired nitric oxide bioavailability were observed.
  • Enhanced atherosclerosis, characterized by larger plaque areas, increased macrophage infiltration, and necrotic cores, was found in double KO mice.
  • Diminished vascular regeneration was noted in EC GC-B KO mice.
  • All observed changes were specific to female mice, with no significant effects in males.

Conclusions:

  • Endothelial CNP/GC-B/cGMP signaling is crucial for protecting against arterial stiffness, systolic hypertension, and atherosclerosis.
  • This signaling pathway also plays a vital role in promoting reparative angiogenesis.
  • A significant sex disparity exists, with diminished CNP/GC-B activity predominantly impacting endothelial dysfunction in female mice.

Keywords:
C-type natriuretic peptideangiogenesisarterial stiffeningatherosclerosiscyclic GMPendothelial dysfunctionsystolic hypertension

More Related Videos

Predicting Amputation using Local Circulating Mononuclear Progenitor Cells in Angioplasty-treated Patients with Critical Limb Ischemia07:25

Predicting Amputation using Local Circulating Mononuclear Progenitor Cells in Angioplasty-treated Patients with Critical Limb Ischemia

Published on: September 22, 2020

3.4K
Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues08:41

Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues

Published on: June 3, 2019

9.8K

Related Concept Videos

Paracrine Signaling01:21

Paracrine Signaling

Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...
54.9K
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.0K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.4K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.4K
Endocrine Signaling01:45

Endocrine Signaling

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
64.2K
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
46.5K