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Cardiovasc. Med."],"abstract":"<jats:p>Maladaptive vascular remodeling is a shared feature of diverse arterial disorders and arises from a self-reinforcing interplay between inflammation and extracellular matrix (ECM) turnover. Matrix metalloproteinase-12 (MMP-12), also known as macrophage elastase, has emerged as a context-dependent mediator within this crosstalk. This review synthesizes current knowledge on the structure, function, and regulation of MMP-12, detailing its multifaceted roles across arterial diseases. Divergent observations across experimental models and clinical settings can be better understood when MMP-12 activity is interpreted in relation to the inflammatory milieu, temporal disease stage, and substrate landscape. Within this framework, MMP-12 can act as a matrix-degrading protease, an amplifier of inflammatory cell recruitment, a regulator of protease cascades, or, in selected settings, a homeostatic modulator of inflammatory resolution. Finally, we discuss the opportunities and translational challenges of MMP-12-targeted strategies, emphasizing that therapeutic interpretation should be constrained by disease context, evidence level, and model heterogeneity.<\/jats:p>","DOI":"10.3389\/fcvm.2026.1825585","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:38:14Z","timestamp":1781757494000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Matrix metalloproteinase-12 in arterial diseases: context-dependent mechanisms of vascular remodeling and therapeutic implications"],"prefix":"10.3389","volume":"13","author":[{"given":"Yifan","family":"Luo","sequence":"first","affiliation":[{"name":"Division of Vascular Surgery, Department of General Surgery, West China Hospital, Sichuan University","place":["Chengdu, Sichuan Province, China"]},{"name":"West China Lecheng Hospital, Sichuan University","place":["Qionghai, 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