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  • Open Daily: 10am - 10pm
    Alley-side Pickup: 10am - 7pm

    3038 Hennepin Ave Minneapolis, MN
    612-822-4611

Open Daily: 10am - 10pm | Alley-side Pickup: 10am - 7pm
3038 Hennepin Ave Minneapolis, MN
612-822-4611
Role of Myd88-Dependent Inflammation in Flow-Mediated Vascular Remodeling.

Role of Myd88-Dependent Inflammation in Flow-Mediated Vascular Remodeling.

Tang, Paul Chun Yung

Paperback

Aging & Elder Care

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ISBN10: 1243570962
ISBN13: 9781243570963
Publisher: Proquest Umi Dissertation Pub
Pages: 168
Weight: 0.69
Height: 0.36 Width: 7.44 Depth: 9.69
Language: English
Vascular remodeling is a mechanism to normalize sustained 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, but not in myeloid differentiation protein-88 (MyD88)-deficient mice. Inward remodeling was associated with MyD88-dependent and superoxide-initiated chemokine and cytokine 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 chemokine and cytokine production, whereas MyD88 expression by bone marrow-derived cells was obligatory for changes in vessel size. In addition, we found that C-X-C chemokine receptor type 3 (CXCR3) expression by macrophages was necessary for flow-mediated vascular remodeling. This was associated with decreased macrophage infiltration in the common carotid arteries of CXCR3-/- mice experiencing decreased luminal flow. Administration of bone marrow derived wild type (WT) myeloid cells was able to rescue macrophage infiltration and vascular remodeling. In addition, matrix metalloproteinase expression was decreased in the carotids of CXCR3 -/- mice. We conclude that there are at least two distinct roles for MyD88 in flow-mediated inward remodeling of conduit arteries and that the production of superoxide-dependent chemokines and cytokines by the endothelium in response to low shear stress act as alarmins for the perivascular accumulation and activation of macrophages. In addition, CXCR3 expressing macrophages may have a distinct phenotype that enabled the remodeling process. Our findings suggest that inflammation is necessary for vascular adaptation to changes in hemodynamic forces.

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