Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model.

Abstract

PURPOSE:

This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation.

METHODS:

Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry.

RESULTS:

Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments.

CONCLUSION:

This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.

• Authors: Liang Geng, Wei Wang, Ying Chen, Jiumei Cao, Lin Lu, Qiujing Chen, Rumin He, Weifeng Shen
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 89 Issue 1 Pg. 72-81 (Aug 2010) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 20621845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• RNA, Messenger
• Collagen
• ADAM Proteins
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• ADAM10 Protein
• ADAM10 protein, rat
• ADAM17 Protein
• Adam17 protein, rat
• Calcium Chloride

Topics

• ADAM Proteins (genetics, metabolism)
• ADAM10 Protein
• ADAM17 Protein
• Animals
• Aortic Aneurysm, Thoracic (chemically induced, metabolism, pathology)
• Calcium Chloride (toxicity)
• Collagen (metabolism)
• Disease Models, Animal
• Immunoenzyme Techniques
• Male
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• RNA, Messenger (genetics)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction