Aortic intimal resident macrophages are essential for maintenance of the non-thrombogenic intravascular state.
Gloria E Hernandez, Feiyang Ma, Guadalupe Martinez, Nadia B Firozabadi, Jocelynda Salvador, Lih Jiin Juang, Jerry Leung, Peng Zhao, Diego A López, Reza Ardehali, Anna E Beaudin, Christian J Kastrup, Matteo Pellegrini, Matthew J Flick, M Luisa Iruela-Arispe
Author Information
Gloria E Hernandez: Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Feiyang Ma: Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Guadalupe Martinez: Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nadia B Firozabadi: Department of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Jocelynda Salvador: Department of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Lih Jiin Juang: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, University of British Columbia, 2185 East Mall, Vancouver, BC, V6T1Z4, Canada.
Jerry Leung: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, University of British Columbia, 2185 East Mall, Vancouver, BC, V6T1Z4, Canada.
Peng Zhao: Department of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Diego A López: Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112.
Reza Ardehali: Department of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Anna E Beaudin: Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112.
Christian J Kastrup: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, University of British Columbia, 2185 East Mall, Vancouver, BC, V6T1Z4, Canada.
Matteo Pellegrini: Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Matthew J Flick: Department of Pathology and Laboratory Medicine, UNC Blood Research Center, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599.
M Luisa Iruela-Arispe: Department of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Leukocytes and endothelial cells frequently cooperate to resolve inflammatory events. In most cases, these interactions are transient in nature and triggered by immunological insults. Here, we report that in areas of disturbed blood flow, aortic endothelial cells permanently and intimately associate with a population of specialized macrophages that are recruited at birth from the closing ductus arteriosus and share the luminal surface with the endothelium becoming interwoven in the tunica intima. Anatomical changes that affect hemodynamics, like in patent ductus arteriosus, alter macrophage seeding to coincide with regions of disturbed flow. Aortic resident macrophages expand via direct cell renewal. Induced-depletion of intimal macrophages led to thrombin-mediated endothelial cell contraction, progressive fibrin accumulation and formation of microthrombi that, once dislodged, caused blockade of vessels in several organs. Together the findings revealed that intravascular resident macrophages are essential to regulate thrombin activity and clear fibrin deposits in regions of disturbed blood flow.
