PMID- 29312500 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1943-8141 (Print) IS - 1943-8141 (Electronic) IS - 1943-8141 (Linking) VI - 9 IP - 12 DP - 2017 TI - Endothelial MMP-9 drives the inflammatory response in abdominal aortic aneurysm (AAA). PG - 5485-5495 AB - Progression of abdominal aortic aneurysm (AAA) is typified by chronic inflammation and extracellular matrix (ECM) degradation of the aortic wall. Vascular inflammation involves complex interactions among inflammatory cells, endothelial cells (ECs), vascular smooth muscle cells (vSMCs), and ECM. Although vascular endothelium and medial neoangiogenesis play a key role in AAA, the molecular mechanisms underlying their involvement are only partially understood. In AAA biopsies, we found increased MMP-9, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which correlated with massive medial neo-angiogenesis (C4d positive staining). In this study, we developed an in vitro model in order to characterize the role of endothelial matrix metalloproteinase-9 (e-MMP-9) as a potential trigger of medial disruption and in the inflammatory response bridging between ECs and vSMC. Lentiviral-mediated silencing of e-MMP-9 through RNA interference inhibited TNF-alpha-mediated activation of NF-kappaB in EA.hy926 human endothelial cells. In addition, EA.hy926 cells void of MMP-9 failed to migrate in a 3D matrix. Moreover, silenced EA.hy926 affected vSMC behavior in terms of matrix remodeling. In fact, also MMP-9 in vSMC resulted inhibited when endothelial MMP-9 was suppressed. FAU - Ramella, Martina AU - Ramella M AD - Department of Health Sciences, Universita del Piemonte Orientale (UPO)Novara, Italy. FAU - Boccafoschi, Francesca AU - Boccafoschi F AD - Department of Health Sciences, Universita del Piemonte Orientale (UPO)Novara, Italy. FAU - Bellofatto, Kevin AU - Bellofatto K AD - Department of Health Sciences, Universita del Piemonte Orientale (UPO)Novara, Italy. FAU - Follenzi, Antonia AU - Follenzi A AD - Department of Health Sciences, Universita del Piemonte Orientale (UPO)Novara, Italy. FAU - Fusaro, Luca AU - Fusaro L AD - Department of Health Sciences, Universita del Piemonte Orientale (UPO)Novara, Italy. FAU - Boldorini, Renzo AU - Boldorini R AD - Department of Health Sciences, Universita del Piemonte Orientale (UPO)Novara, Italy. FAU - Casella, Francesco AU - Casella F AD - Department of Vascular Surgery, Ospedale Maggiore della CaritaNovara, Italy. FAU - Porta, Carla AU - Porta C AD - Department of Vascular Surgery, Ospedale Maggiore della CaritaNovara, Italy. FAU - Settembrini, Piergiorgio AU - Settembrini P AD - Division of Vascular Surgery, Universita di MilanoMilan, Italy. FAU - Cannas, Mario AU - Cannas M AD - Department of Health Sciences, Universita del Piemonte Orientale (UPO)Novara, Italy. LA - eng PT - Journal Article DEP - 20171215 PL - United States TA - Am J Transl Res JT - American journal of translational research JID - 101493030 PMC - PMC5752898 OTO - NOTNLM OT - Abdominal aortic aneurysm OT - MMP-9 silencing OT - endothelium dysfunction OT - inflammatory response OT - vascular remodeling COIS- None. EDAT- 2018/01/10 06:00 MHDA- 2018/01/10 06:01 PMCR- 2017/12/15 CRDT- 2018/01/10 06:00 PHST- 2017/06/21 00:00 [received] PHST- 2017/10/15 00:00 [accepted] PHST- 2018/01/10 06:00 [entrez] PHST- 2018/01/10 06:00 [pubmed] PHST- 2018/01/10 06:01 [medline] PHST- 2017/12/15 00:00 [pmc-release] PST - epublish SO - Am J Transl Res. 2017 Dec 15;9(12):5485-5495. eCollection 2017.