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Transverse Aortic Constriction in Mice
Published on: April 22, 2010
Matrix metalloproteinase-7 and ADAM-12 (a disintegrin and metalloproteinase-12) define a signaling axis in
Xiang Wang1, Fung Lan Chow, Tatsujiro Oka
1Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
Circulation
|April 29, 2009
Summary
This study reveals a new signaling pathway involving matrix metalloproteinase-7 (MMP-7) and ADAM-12 that drives hypertension and cardiac hypertrophy. Targeting this MMP-7/ADAM-12 axis offers potential therapeutic strategies for cardiovascular disorders.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biochemistry
Background:
- Gq protein-coupled receptor overstimulation drives hypertension and hypertrophy.
- Matrix metalloproteinase-7 (MMP-7) and ADAM-12 are implicated in these cardiovascular processes.
- A novel signaling axis between MMP-7 and ADAM-12 is investigated.
Purpose of the Study:
- To elucidate the role of MMP-7 in hypertension and cardiac hypertrophy.
- To determine the relationship between MMP-7 and ADAM-12 in cardiovascular regulation.
- To explore the therapeutic potential of targeting the MMP-7/ADAM-12 axis.
Main Methods:
- Rodent models of acute, long-term, and spontaneous hypertension.
- Pharmacological inhibition, RNA interference, and gene knockout of MMP-7.
- Quantitative reverse-transcription polymerase chain reaction to assess gene expression.
Main Results:
- Vascular MMP-7 activation is required for acute hypertension induced by vasoconstrictors.
- MMP-7 knockdown attenuated hypertension and cardiac hypertrophy in spontaneously hypertensive rats.
- MMP-7 controls ADAM-12 transcription, which is implicated in cardiac hypertrophy.
Conclusions:
- Hypertension and hypertrophy signaling involve MMP-7 through posttranscriptional and transcriptional mechanisms.
- MMP-7 is transcriptionally linked to ADAM-12, forming a novel signaling axis.
- Targeting the MMP-7/ADAM-12 axis may offer therapeutic benefits for hypertensive disorders.
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