2026-06-14T03:31:33Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/66842024-10-31T11:52:17Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Clemente, Cristina author Rius, Cristina author Alonso-Herranz, Laura author Martin-Alonso, Mara author Pollan, Angela author Camafeita, Emilio author Martinez, Fernando author Mota, Ruben A. author Nunez, Vanessa author Rodriguez, Cristina author Seiki, Motoharu author Martinez-Gonzalez, Jose author Andres, Vicente author Ricote, Mercedes author Arroyo, Alicia G author 2018 Matrix metalloproteinases are involved in vascular remodeling. Little is known about their immune regulatory role in atherosclerosis. Here we show that mice deficient for MT4-MMP have increased adherence of macrophages to inflamed peritonea, and larger lipid deposits and macrophage burden in atherosclerotic plaques. We also demonstrate that MT4-MMP deficiency results in higher numbers of patrolling monocytes crawling and adhered to inflamed endothelia, and the accumulation of Mafb+ apoptosis inhibitor of macrophage (AIM)+ macrophages at incipient atherosclerotic lesions in mice. Functionally, MT4-MMP-null Mafb+ AIM+ peritoneal macrophages express higher AIM and scavenger receptor CD36, are more resistant to apoptosis, and bind acLDL avidly, all of which contribute to atherosclerosis. CCR5 inhibition alleviates these effects by hindering the enhanced recruitment of MT4-MMP-null patrolling monocytes to early atherosclerotic lesions, thus blocking Mafb+ AIM+ macrophage accumulation and atherosclerosis acceleration. Our results suggest that MT4-MMP targeting may constitute a novel strategy to boost patrolling monocyte activity in early inflammation. Nat Commun. 2018; 9(1):910 10.1038/s41467-018-03351-4 2041-1723 Nature Communications 29500407 http://hdl.handle.net/20.500.12105/6684 MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis