Molecular imaging of MMP activity discriminates unstable from stable plaque phenotypes in shear-stress induced murine

Robert Seifert1,2, Michael T Kuhlmann1, Sarah Eligehausen1

  • 1European Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.

Plos One
|October 11, 2018
PubMed
Abstract

Insights

Matrix metalloproteinase (MMP) imaging effectively identified unstable atherosclerotic plaques in mice. This molecular imaging approach visualizes differences in MMP activity, aiding in the characterization of rupture-prone plaques.

Area of Science:

  • Cardiovascular Research
  • Molecular Imaging
  • Biomedical Engineering

Background:

  • Atherosclerotic plaque rupture is a major cause of ischemic events.
  • Identifying unstable plaques for prevention is a clinical challenge.
  • Matrix metalloproteinases (MMPs) are implicated in plaque destabilization.

Purpose of the Study:

  • To evaluate MMP imaging for discriminating unstable from stable atherosclerotic plaque phenotypes.
  • To assess the utility of MMP inhibitor-based photoprobes in atherosclerosis research.

Main Methods:

  • ApoE deficient mice were used with a cuff model to induce unstable (upstream) and stable (downstream) plaques.
  • MMP inhibitor-based photoprobe (Cy5.5-AF443) was administered intravenously.
  • In situ and ex vivo fluorescence reflectance imaging, immunohistochemistry, and ELISA were performed.

Main Results:

  • Significantly higher Cy5.5-AF443 uptake was observed in unstable plaques compared to stable plaques.
  • Unstable plaques showed increased presence of macrophages, MMP-2, and MMP-9.
  • MMP-2 concentrations were significantly elevated in unstable plaques.

Conclusions:

  • MMP-2 and MMP-9 activities are significantly higher in unstable atherosclerotic plaques.
  • MMP inhibitor-based fluorescence molecular imaging can visualize differences in shear stress-induced atherosclerosis.
  • This imaging modality holds promise for characterizing rupture-prone plaques.

Related Concept Videos

Shearing Stress01:19

Shearing Stress

Shearing stress, denoted by the Greek letter tau (τ), is stress caused by forces acting transversely on an object. These forces create internal ones within the entity in the plane where the external forces are applied. The resultant of these internal forces is the shear in the section.
The average shearing stress can be calculated by dividing the shear by the area of the cross-section.
2.0K
Shearing Stresses in a Beam: Problem Solving01:14

Shearing Stresses in a Beam: Problem Solving

A cantilever beam with a rectangular cross-section under distributed and point loads experiences shearing stresses. The analysis begins by identifying the loads acting on the beam. Then, the reactions at the beam's fixed end are calculated using equilibrium equations. The vertical reaction is a combination of the distributed and point loads, while the moment reaction is the sum of their moments. The shear force distribution along the beam, resulting from these loads, is established by creating...
673
Elastic Strain Energy for Shearing Stresses01:20

Elastic Strain Energy for Shearing Stresses

As discussed in previous lessons, strain energy in a material is the energy stored when it is elastically deformed, a concept crucial in materials science and mechanical engineering. This energy results from the internal work done against the cohesive forces within the material. When a material undergoes shearing stress and corresponding shearing strain, the strain energy density, which is the energy stored per unit volume, is calculated. Within the elastic limit, where the stress is...
516
Stereotypes, Prejudice, and Discrimination02:55

Stereotypes, Prejudice, and Discrimination

Humans are very diverse and although we share many similarities, we also have many differences. The social groups we belong to help form our identities (Tajfel, 1974). These differences may be difficult for some people to reconcile, which may lead to prejudice toward people who are different. Prejudice is a negative attitude and feeling toward an individual based solely on one’s membership in a particular social group (Allport, 1954; Brown, 2010). Prejudice is common against people who...
95.4K
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
412
Atherosclerosis I: Introduction01:30

Atherosclerosis I: Introduction

Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
1.1K