MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis
Por:
Clemente, C, Rius, C, Alonso-Herranz, L, Martin-Alonso, M, Pollan, A, Camafeita, E, Martinez, F, Mota, RA, Nunez, V, Rodriguez, C, Seiki, M, Martinez-Gonzalez, J, Andres, V, Ricote, M, Arroyo, AG
Publicada:
2 mar 2018
Resumen:
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.
Filiaciones:
Clemente, C:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Matrix Metalloproteinases Angiogenesis & Inflamma, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Rius, C:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Mol & Genet Cardiovasc Pathophysiol Grp, Melchor Fernandez Almagro 3, Madrid 28029, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Alonso-Herranz, L:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Nucl Receptor Signaling Grp, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Martin-Alonso, M:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Matrix Metalloproteinases Angiogenesis & Inflamma, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Pollan, A:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Matrix Metalloproteinases Angiogenesis & Inflamma, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Camafeita, E:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Prote Unit, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Martinez, F:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Bioinformat Unit, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Mota, RA:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Matrix Metalloproteinases Angiogenesis & Inflamma, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Nunez, V:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Nucl Receptor Signaling Grp, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Rodriguez, C:
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Hosp Santa Creu & Sant Pau, Inst Recerca, Programa ICCC, IIB St Pau, St Antoni Maria Claret 167, Barcelona 08025, Spain
Seiki, M:
Univ Tokyo, Inst Med Sci, Div Canc Cell Res, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan
Martinez-Gonzalez, J:
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Inst Invest Biomed Barcelona IIBB CSIC, IIB St Pau, Rossello 161, Barcelona 08036, Spain
Andres, V:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Mol & Genet Cardiovasc Pathophysiol Grp, Melchor Fernandez Almagro 3, Madrid 28029, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Madrid, Spain
Ricote, M:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Nucl Receptor Signaling Grp, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Arroyo, AG:
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Matrix Metalloproteinases Angiogenesis & Inflamma, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Ctr Invest Biol CIB CSIC, Ramiro de Maeztu 9, Madrid 28040, Spain
Gold, Green Published
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