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

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.

Effective litmus gene test for monitoring the quality of blood samples: Application to Alzheimer’s disease diagnostics

“…The SPC25 gene encodes a component of the NDC80 kinetochore complex that may be involved in kinetochore-microtubule interactions and spindle checkpoint activity 31 . Although there was a report that SPC25 was upregulated in aged monocytes from rats 32 , it is not known if SPC25 is associated with neurodegenerative diseases such as AD. The involvement of SPC25 in AD pathogenesis remains to be determined.…”

Oxidative stress-induced cellular senescence desensitizes cell growth and migration of vascular smooth muscle cells through down-regulation of platelet-derived growth factor receptor-beta

“…Vazquez-Padron et al mentioned that aging exacerbated wire injury-induced neointimal formation and increased VSMC proliferation in aged female C57BL/6 mice (18 months) [21]. Increased neointimal thickening in the carotid artery after balloon angioplasty was also found in aged Fischer 344 rats (22~24 months) [22–24]. These controversial results of an aging effect on the restenosis prevalence may have been caused by differences in patient characteristics, such as race, gender, selection criteria (e.g., comorbidity status), surgical interventions (e.g., balloon angioplasty vs. vascular stenting), medicinal interventions, and lifestyle factors (e.g., smoking).…”

Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers

“…This is in line with a plethora of changes reported for monocytes and macrophages upon aging in humans and rodents. For example, old rats enrich for CD11b + monocytes expressing IFNγ (63), while elderly human PB accumulate so-called intermediate and non-classical monocytes producing high levels of TNFα (8). Aging also impairs phagocytosis of myeloid cells, such as human neutrophils and CD14 + monocytes and murine PC macrophages (8, 11), and the responses of monocytes and macrophages to IFNγ and TLR stimulations (64-66).…”