RECK Overexpression in Smooth Muscle Cells Aggravates Abdominal Aortic Aneurysm Progression

RECK (Reversion-inducing Cysteine-rich Protein with Kazal Motifs) is a known negative regulator of matrix metalloproteinases (MMPs), which play a key role in extracellular matrix (ECM) degradation and vascular remodeling. Abdominal aortic aneurysm (AAA) is a devastating vascular disease characterized by the permanent localized dilation of the abdominal aorta by > 1.5 times its normal diameter. A common pathophysiological feature of AAA development is the ECM degradation of the aortic wall by MMPs. Therefore, we hypothesized that RECK overexpression in smooth muscle cells (SMCs) protects against AAA by suppressing MMP activity. We tested this hypothesis in constitutive ApoE knockout (KO) male mice with tamoxifen-inducible SMC-specific RECK overexpression or SMC-specific RECK KO. All mice (16-22 weeks old) were fed tamoxifen for 2 weeks (40 mg/kg/day) followed by the continuous infusion of angiotensin II (via an osmotic minipump, s.c., 1000 ng/kg/min for 28 days), and AAA development was compared to their corresponding RECK wild-type littermate controls. All differences reported herein are significant at p<0.05. Contrary to expectations, SMC-RECK overexpression led to increased aortic diameters and an incidence of AAA with significantly elevated mortality rates. In comparison, SMC-RECK KO had no significant effects on AAA incidence or mortality. These findings suggest that, rather than being protective, RECK overexpression in SMCs exacerbates AAA progression. Further analysis is needed to determine the underlying mechanisms, including potential changes in MMP activity or alternative signaling pathways. Our study challenges the conventional role of RECK as an MMP inhibitor in AAA pathology and highlights its unexpected impact on disease progression. These preliminary data emphasize the complexity of ECM regulation in AAA and suggest that RECK may influence aneurysm development through mechanisms beyond MMP inhibition. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.