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Review
. 2021 Feb 22;117(3):663-673.
doi: 10.1093/cvr/cvaa062.

Macrophage lineages in heart valve development and disease

Andrew J Kim  1 , Na Xu  1 , Katherine E Yutzey  1
Affiliations
Review

Macrophage lineages in heart valve development and disease

Andrew J Kim et al. Cardiovasc Res. .

Abstract

Heterogeneous macrophage lineages are present in the aortic and mitral valves of the heart during development and disease. These populations include resident macrophages of embryonic origins and recruited monocyte-derived macrophages prevalent in disease. Soon after birth, macrophages from haematopoietic lineages are recruited to the heart valves, and bone marrow transplantation studies in mice demonstrate that haematopoietic-derived macrophages continue to invest adult valves. During myxomatous heart valve disease, monocyte-derived macrophages are recruited to the heart valves and they contribute to valve degeneration in a mouse model of Marfan syndrome. Here, we review recent studies of macrophage lineages in heart valve development and disease with discussion of clinical significance and therapeutic applications.

Keywords: Heart valve; Macrophage; Myxomatous valve disease; Valve development.

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Figures

Figure 1
Figure 1
Macrophage origins in developing heart valves. The sources of macrophages in the cardiovascular system during development include the yolk sac and AGM region in embryos, the foetal liver in foetuses and newborns, and the bone marrow during definitive haematopoiesis after birth. The right panel shows a mouse aortic valve at 1 month-of-age with CD45+ cells stained red that are predominantly heterogeneous macrophages.
Figure 2
Figure 2
Heart valve development and disease. During embryonic development, endocardial cushions are present in the outflow tract that elongate and stratify into valve leaflets after birth. Valve layers consist of fibrosa (yellow), spongiosa (blue), and atrialis (black). Bottom panels depict myxomatous alterations associated with connective tissue mutations (left) and calcification of aortic valves characteristic of aortic stenosis (right).
Figure 3
Figure 3
Macrophages in mouse heart development and MVD. (A–C) Localization of embryonic (CD206+) and postnatal (MHCII+) macrophage populations and localization in the developing mouse aortic valve change after birth. (Right panels) Increased numbers and altered localization of macrophages in myxomatous mitral valves of MFS mice (Fbn1C1039G/+) at 2 months-of-age.
Figure 4
Figure 4
CCR2 depletion as a therapeutic approach for MVD. Increased recruited macrophages (CCR2+) are present in myxomatous mitral valves that express CCL2. Recruited macrophages are not present in CCR2-null mice and they have reduced myxomatous valve degeneration as adults.
See this image and copyright information in PMC

References

    1. Lavine KJ, Pinto AR, Epelman S, Kopecky BJ,, Clemente-Casares X, Godwin J, Rosenthal N, Kovacic JC. The macrophage in cardiac homeostasis and disease: JACC macrophage in CVD series (part 4). J Am Coll Cardiol 2018;72:2213–2230. - PMC - PubMed
    1. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119–1131. - PubMed
    1. Nasir K, Katz R, Takasu J, Shavelle DM, Detrano R, Lima JA, Blumenthal RS, O’Brien K, Budoff MJ. Ethnic differences between extra-coronary measures on cardiac computed tomography: multi-ethnic study of atherosclerosis (MESA). Atherosclerosis 2008;198:104–114. - PMC - PubMed
    1. Iung B, Vahanian A. Epidemiology of valvular heart disease in the adult. Nat Rev Cardiol 2011;8:162–172. - PubMed
    1. Levine RA, Hagege AA, Judge DP, Padala M, Dal-Bianco JP, Aikawa E, Beaudoin J, Bischoff J, Bouatia-Naji N, Bruneval P, Butcher JT, Carpentier A, Chaput M, Chester AH, Clusel C, Delling FN, Dietz HC, Dina C, Durst R, Fernandez-Friera L, Handschumacher MD, Jensen MO, Jeunemaitre XP, Le Marec H, Le Tourneau T, Markwald RR, Merot J, Messas E, Milan DP, Neri T, Norris RA, Peal D, Perrocheau M, Probst V, Puceat M, Rosenthal N, Solis J, Schott JJ, Schwammenthal E, Slaugenhaupt SA, Song JK, Yacoub MH; Leducq Mitral Transatlantic Network. Mitral valve disease–morphology and mechanisms. Nat Rev Cardiol 2015;12:689–710. - PMC - PubMed

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