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Origin of Matrix-Producing Cells That Contribute to Aortic Fibrosis in Hypertension. Hypertension 2016 Feb;67(2):461-8

Date

12/24/2015

Pubmed ID

26693821

Pubmed Central ID

PMC4713264

DOI

10.1161/HYPERTENSIONAHA.115.06123

Scopus ID

2-s2.0-84954370789   42 Citations

Abstract

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.

Author List

Wu J, Montaniel KR, Saleh MA, Xiao L, Chen W, Owens GK, Humphrey JD, Majesky MW, Paik DT, Hatzopoulos AK, Madhur MS, Harrison DG



MESH terms used to index this publication - Major topics in bold

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