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. 2015 Jul 10;6(19):17054-64.
doi: 10.18632/oncotarget.3881.

Age-related changes in monocytes exacerbate neointimal hyperplasia after vascular injury

Laisel Martinez  1 , Camilo Gomez  1 , Roberto I Vazquez-Padron  1
Affiliations

Age-related changes in monocytes exacerbate neointimal hyperplasia after vascular injury

Laisel Martinez et al. Oncotarget. .

Abstract

Neointimal hyperplasia is the leading cause of restenosis after endovascular interventions. It is characterized by the accumulation of myofibroblast-like cells and extracellular matrix in the innermost layer of the wall and is exacerbated by inflammation. Monocytes from either young or aged rats were applied perivascularly to injured vascular walls of young recipient animals. Monocytes from aged rats, but not young donors, increased neointima thickness. Accordingly, the gene expression profiles of CD11b+ monocytes from aged rats showed significant up-regulation of genes involved in cellular adhesion, lipid degradation, cytotoxicity, differentiation, and inflammation. These included cadherin 13 (Cdh13), colony stimulating factor 1 (Csf1), chemokine C-X-C motif ligand 1 (Cxcl1), endothelial cell-selective adhesion molecule (Esam), and interferon gamma (Ifng). In conclusion, our results suggest that the increased inflammatory and adhesive profile of monocytes contributes to pathological wall remodeling in aged-related vascular diseases.

Keywords: age; balloon injury; gene expression; monocytes; neointimal hyperplasia.

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Conflict of interest statement

CONFLICTS OF INTERESTS

The authors indicate no potential conflicts of interests.

Figures

Figure 1
Figure 1. Aging causes monocytosis in rats
A. Representative flow cytometry analysis of purified monocytes. B.Cell counts ± SEM of monocytes, granulocytes and lymphocytes in young and aged rats (n = 3 per group). Numbers are expressed as percentages of peripheral blood mononuclear cells. *p < 0.05.
Figure 2
Figure 2. Monocytes from aged rats exacerbate post-injury neointimal hyperplasia in young arteries
A-B. Equal numbers of monocytes from young and aged rats were suspended in Matrigel and exogenously seeded around arteries prior to balloon injury. A. Hematoxylin and Eosin and B. SMA stained cross-sections of injured arteries treated with Matrigel alone, or monocytes from young and aged donors, and harvested 21 days after injury. The neointima layer is delineated by arrows. C. Neointima-to-media ratios of the three experimental groups expressed as mean ratio ± SEM (n = 6 per group). *p < 0.05.
Figure 3
Figure 3. Perivascular delivery of monocytes from young and aged rats increased the number of CD68+ macrophages in the adventitia
A. Immunofluorescent staining of injured arteries 21 days after surgery using an anti-CD68 antibody. CD68+ macrophages are shown in yellow, while nuclei were counter-stained with DAPI (blue). B. Number of macrophages per section in the three experimental groups. Bars represent the mean ± SEM (n = 4 per group). *p < 0.05.
Figure 4
Figure 4. Aging induces significant gene expression differences in rat monocytes
A. Confirmatory qRT-PCR for cadherin 13 (Cdh13) and secreted frizzled-related protein 1 (Sfrp1) in monocytes. Gene expression (GE) is expressed in fold change of aged vs. young as calculated using the ddCT method. B. Immunofluorescent staining of young and aged monocytes using antibodies against CDH13 and SFRP1.
See this image and copyright information in PMC

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