Origin of Matrix-Producing Cells That Contribute to Aortic Fibrosis in Hypertension.

Wu J, Montaniel KR, Saleh MA, Xiao L, Chen W, Owens GK, Humphrey JD, Majesky MW, Paik DT, Hatzopoulos AK, Madhur MS, Harrison DG
Hypertension. 2016 67 (2): 461-8

PMID: 26693821 · PMCID: PMC4713264 · DOI:10.1161/HYPERTENSIONAHA.115.06123

Various hypertensive stimuli lead to exuberant adventitial collagen deposition in large arteries, exacerbating blood pressure elevation and end-organ damage. Collagen production is generally attributed to resident fibroblasts; however, other cells, including resident and bone marrow-derived stem cell antigen positive (Sca-1(+)) cells and endothelial and vascular smooth muscle cells, can produce collagen and contribute to vascular stiffening. Using flow cytometry and immunofluorescence, we found that adventitial Sca-1(+) progenitor cells begin to produce collagen and acquire a fibroblast-like phenotype in hypertension. We also found that bone marrow-derived cells represent more than half of the matrix-producing cells in hypertension, and that one-third of these are Sca-1(+). Cell sorting and lineage-tracing studies showed that cells of endothelial origin contribute to no more than one fourth of adventitial collagen I(+) cells, whereas those of vascular smooth muscle lineage do not contribute. Our findings indicate that Sca-1(+) progenitor cells and bone marrow-derived infiltrating fibrocytes are major sources of arterial fibrosis in hypertension. Endothelial to mesenchymal transition likely also contributes, albeit to a lesser extent and pre-existing resident fibroblasts represent a minority of aortic collagen-producing cells in hypertension. This study shows that vascular stiffening represents a complex process involving recruitment and transformation of multiple cells types that ultimately elaborate adventitial extracellular matrix.

© 2015 American Heart Association, Inc.

MeSH Terms (16)

Animals Aorta, Thoracic Aortic Diseases Cells, Cultured Collagen Disease Models, Animal Extracellular Matrix Proteins Fibroblasts Fibrosis Flow Cytometry Hypertension Immunohistochemistry Male Mice Mice, Inbred C57BL Muscle, Smooth, Vascular

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