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

PurposeThis study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl2)-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.MethodsThoracic aorta of male Sprague–Dawley rats was exposed to 0.5 M CaCl2 or normal saline (NaCl). After 12 weeks, animals were euthanized, and CaCl2-treated, CaCl2-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.ResultsDespite similar external diameters among CaCl2-treated, non-CaCl2-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 CaCl2-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl2-treated segments (all p < 0.01), with trends of elevation in CaCl2-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 CaCl2-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments.ConclusionThis study establishes a TAA model by periarterial CaCl2 exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.