MFAP4 Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation Through Regulation of Macrophage Infiltration and Activity

• DOI: 10.3389/fcvm.2021.764337
• Publication Date: 2021-11-05T10:32:27Z
• Authors: Bartosz Pilecki; Paulo V. S. D. de...; Katrine L. Kirket...; Anders Schlosser; Karin Kejling; Magdalena Dubik; Nicklas P. Madsen; Jane Stubbe; Pernille B. L. Ha...; Thomas L. Andersen; Jesper B. Moeller; Niels Marcussen; Vasco Azevedo; Svend Hvidsten; Christina Baun; Guo-Ping Shi; Jes S. Lindholt; Grith L. Sorensen
• Keywords: Apolipoprotein E; Monocyte

Objective: Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the wall. Microfibrillar-associated protein 4 (MFAP4) an extracellular matrix (ECM) involved in induction remodeling. This study aimed to investigate if MFAP4 facilitates development AAA characterize underlying MFAP4-mediated mechanisms. Approach Results: Double apolipoprotein E- Mfap4-deficient (ApoE-/-Mfap4-/-) control E-deficient (ApoE-/-) mice were infused subcutaneously with angiotensin II (Ang II) for 28 days. Mfap4 expression was localized within adventitial medial layers upregulated after Ang treatment. While II-induced blood pressure increase independent genotype, ApoE-/-Mfap4-/- exhibited significantly lower incidence reduced maximal diameter compared ApoE-/- littermates. The AAAs further macrophage infiltration, metalloproteinase (MMP)-2 MMP-9 activity, proliferative collagen content, elastic membrane disruption. deficiency also attenuated activation integrin- TGF-β-related signaling layer tissues. Finally, stimulation promoted human monocyte migration activity macrophage-like THP-1 cells. Conclusion: demonstrates that induces macrophage-rich inflammation, MMP maladaptive remodeling ECM vessel wall, leading acceleration progression. Collectively, our findings suggest essential aggravator pathology acts through regulation influx production.