MyD88-dependent, superoxide-initiated inflammation is necessary for flow-mediated inward remodeling of conduit arteries.
Vascular remodeling normalizes abnormal hemodynamic stresses through structural changes affecting vessel size and wall thickness. We investigated the role of inflammation in flow-mediated vascular remodeling using a murine model of partial outflow reduction without flow cessation or neointima formation. Common carotid arteries decreased in size after ipsilateral external carotid artery ligation in wild-type mice, but not in myeloid differentiation protein-88 (MyD88)-deficient mice. Inward remodeling was associated with MyD88-dependent and superoxide-initiated cytokine and chemokine production, as well as transient adventitial macrophage accumulation and activation. Macrophage depletion prevented flow-mediated inward vascular remodeling. Expression of MyD88 by intrinsic vascular cells was necessary for cytokine and chemokine production and changes in vessel size, whereas MyD88 expression by bone marrow-derived cells was obligatory for changes in vessel size. We conclude that there are at least two distinct roles for MyD88 in flow-mediated inward remodeling of conduit arteries. Our findings suggest that inflammation is necessary for vascular adaptation to changes in hemodynamic forces.
Tang
Paul C Y
PC
Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06510, USA.
Qin
Lingfeng
L
Zielonka
Jacek
J
Zhou
Jing
J
Matte-Martone
Catherine
C
Bergaya
Sonia
S
van Rooijen
Nico
N
Shlomchik
Warren D
WD
Min
Wang
W
Sessa
William C
WC
Pober
Jordan S
JS
Tellides
George
G
D000818:Animals; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000033:anatomy & histology / Q000276:immunology / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006439:Hemodynamics; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D012039:Regional Blood Flow / Q000502:physiology; D013481:Superoxides / Q000276:immunology*
D018925:Chemokines; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D013481:Superoxides