Related Experiment Video
Updated: Jun 7, 2026
Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
Published on: September 28, 2015
Transgenic expression of matrix metalloproteinase-2 induces coronary artery ectasia
Sia Dahi1, Joel S Karliner, Rajabrata Sarkar
1The Department of Surgery, San Francisco Department of Veterans Affairs Medical Center/University of California San Francisco and Northern California Institute for Research and Education, San Francisco, CA 94121, USA.
Insights
Coronary artery ectasia (CAE) is linked to matrix metalloproteinase-2 (MMP-2). This study shows MMP-2 causes CAE in mice, suggesting it initiates the human disorder.
Area of Science:
- Cardiovascular Biology
- Vascular Pathology
- Enzyme Function in Disease
Background:
- Coronary artery ectasia (CAE) is often seen with atherosclerosis but may stem from systemic vascular issues.
- Aneurysmal vascular diseases involve inflammatory cytokines and enzymes degrading vascular walls.
- Matrix metalloproteinase-2 (MMP-2) degrades elastin and is implicated in aortic aneurysms.
Purpose of the Study:
- To investigate the role of MMP-2 in the development of coronary artery ectasia (CAE).
- To characterize CAE in a novel transgenic mouse model expressing cardiac-specific active MMP-2.
- To determine if MMP-2 plays a critical role in CAE pathogenesis.
Main Methods:
- Engineered transgenic mice for cardiac-specific expression of active MMP-2.
- Quantified coronary artery diameters, structure, and elastin integrity.
- Utilized latex casting to assess coronary artery volumes and branching patterns.
- Examined vascular expression of the MMP-2 transgene and inflammatory cell infiltration.
Main Results:
- MMP-2 transgenic mice exhibited increased mid-ventricular coronary luminal areas and aneurysmal dilation.
- Compromised coronary vascular elastin integrity and perivascular fibrosis were observed.
- No evidence of atherosclerosis was found in the transgenic model.
- Latex casts revealed coronary artery ectasia with fusiform dilatation.
Conclusions:
- The MMP-2 transgenic mouse model closely replicates human CAE.
- Enhanced MMP-2 expression initiates coronary artery ectasia.
- MMP-2 plays a critical and initiating role in the pathogenesis of coronary artery ectasia.
Abstract:
Coronary artery ectasia (CAE) is generally diagnosed in patients undergoing arteriography for presumptive atherosclerotic coronary artery disease. CAE is commonly considered as a variant of atherosclerotic disease; however, recent studies suggest that CAE is the result of a systemic vascular disorder. There is increasing evidence that aneurysmal vascular disease is a systemic disorder characterized by enhanced expression of pro-inflammatory cytokines and increased synthesis of enzymes capable of degrading elastin and other components of the vascular wall. Matrix metalloproteinase-2 degrades a number of extracellular substrates, including elastin and has been shown to play a critical role in the development of abdominal aortic aneurysms. This study characterizes the development of CAE in a unique murine transgenic model with cardiac-specific expression of active MMP-2. Transgenic mice were engineered to express an active form of MMP-2 under control of the α-myosin heavy chain promoter. Coronary artery diameters were quantified, along with studies of arterial structure, elastin integrity and vascular expression of the MMP-2 transgene. Latex casts quantified total coronary artery volumes and arterial branching. Mid-ventricular coronary luminal areas were increased in the MMP-2 transgenics, coupled with foci of aneurysmal dilation, ectasia and perivascular fibrosis. There was no evidence for atherogenesis. Coronary vascular elastin integrity was compromised and coupled with inflammatory cell infiltration. Latex casts of the coronary arteries displayed ectasia with fusiform dilatation. The MMP-2 transgenic closely replicates human CAE and supports a critical and initiating role for this enzyme in the pathogenesis of this disorder.
