Related Experiment Video

Updated: Aug 15, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

A proatherogenic role for cGMP-dependent protein kinase in vascular smooth muscle cells

Wiebke Wolfsgruber1, Susanne Feil, Sabine Brummer

  • 1Institut für Pharmakologie und Toxikologie, Technische Universität, Biedersteiner Strasse 29, 80802 Munich, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|November 5, 2003
PubMed

Insights

Smooth muscle cGMP-dependent protein kinase I (cGKI) promotes atherosclerosis. Inhibiting cGKI in vascular cells may offer a new therapeutic strategy for treating this cardiovascular disease.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Vascular Cell Biology

Background:

  • Nitric oxide (NO) has complex roles in atherosclerosis.
  • The precise mechanisms by which NO influences atherosclerosis are not fully elucidated.
  • cGMP-dependent protein kinase I (cGKI) is a key mediator of NO signaling in vascular smooth muscle cells (SMCs).

Purpose of the Study:

  • To investigate the role of smooth muscle cGKI in the development of atherosclerosis.
  • To determine if cGKI in SMCs promotes or protects against atherogenesis.
  • To explore the molecular mechanisms by which cGKI influences SMC behavior in the context of atherosclerosis.

Main Methods:

  • Selective postnatal ablation of cGKI in mouse SMCs.
  • Cell-fate mapping studies in mice.
  • In vitro activation of endogenous cGKI in primary aortic SMCs.
  • Analysis of proatherogenic markers including proliferation, adhesion molecules, and signaling pathways.

Main Results:

  • Ablation of SMC-specific cGKI significantly reduced atherosclerotic lesion area in mice.
  • Cell-fate mapping revealed cGKI's involvement in the development of SMC-derived plaque cells.
  • Activated cGKI in SMCs increased proliferation, vascular cell adhesion molecule-1, peroxisome proliferator-activated receptor gamma, and PI3K/Akt signaling.
  • Activated cGKI also decreased plasminogen activator inhibitor 1 mRNA levels.

Conclusions:

  • Smooth muscle cGKI plays a critical role in promoting atherogenesis.
  • cGKI mediates proatherogenic changes in SMCs both in vitro and in vivo.
  • Inhibition of smooth muscle cGKI may represent a potential therapeutic target for atherosclerosis.

More Related Videos

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro08:28

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Published on: February 15, 2022

Isolation of Intrapulmonary Artery and Smooth Muscle Cells to Investigate Vascular Responses07:56

Isolation of Intrapulmonary Artery and Smooth Muscle Cells to Investigate Vascular Responses

Published on: June 8, 2022

Related Concept Videos

Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
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 cells.
Two...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
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 to...