Ex vivo foam cell formation is enhanced in monocytes from older individuals by both extrinsic and intrinsic mechanisms

Thomas A. Angelovich, Margaret D.Y. Shi, Jingling Zhou, Anna Maisa, Anna C. Hearps, Anthony Jaworowski

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Aging is the strongest predictor of cardiovascular diseases such as atherosclerosis, which are the leading causes of morbidity and mortality in elderly men. Monocytes play an important role in atherosclerosis by differentiating into foam cells (lipid-laden macrophages) and producing atherogenic proinflammatory cytokines. Monocytes from the elderly have an inflammatory phenotype that may promote atherosclerotic plaque development; here we examined whether they are more atherogenic than those from younger individuals.Using an in vitro model of monocyte transmigration and foam cell formation, monocytes from older men (median age [range]: 75 [58-85] years, n = 20) formed foam cells more readily than those of younger men (32 [23-46] years, n = 20) (P < 0.003) following transmigration across a TNF-activated endothelial monolayer. Compared to young men, monocytes from the elderly had impaired cholesterol efflux and lower expression of regulators of cholesterol transport and metabolism. Foam cell formation was enhanced by soluble factors in serum from older men, but did not correlate with plasma lipid levels. Of the three subsets, intermediate monocytes formed the most foam cells.Therefore, both cellular changes to monocytes and soluble plasma factors in older men primes monocytes for foam cell formation following transendothelial migration, which may contribute to enhanced atherosclerosis in this population.

Original languageEnglish
Pages (from-to)17-26
Number of pages10
JournalExperimental Gerontology
Volume80
DOIs
Publication statusPublished - 1 Jul 2016

Keywords

  • Age-related disease
  • Atherosclerosis
  • Foam cells
  • Inflammation
  • Monocytes

Cite this

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title = "Ex vivo foam cell formation is enhanced in monocytes from older individuals by both extrinsic and intrinsic mechanisms",
abstract = "Aging is the strongest predictor of cardiovascular diseases such as atherosclerosis, which are the leading causes of morbidity and mortality in elderly men. Monocytes play an important role in atherosclerosis by differentiating into foam cells (lipid-laden macrophages) and producing atherogenic proinflammatory cytokines. Monocytes from the elderly have an inflammatory phenotype that may promote atherosclerotic plaque development; here we examined whether they are more atherogenic than those from younger individuals.Using an in vitro model of monocyte transmigration and foam cell formation, monocytes from older men (median age [range]: 75 [58-85] years, n = 20) formed foam cells more readily than those of younger men (32 [23-46] years, n = 20) (P < 0.003) following transmigration across a TNF-activated endothelial monolayer. Compared to young men, monocytes from the elderly had impaired cholesterol efflux and lower expression of regulators of cholesterol transport and metabolism. Foam cell formation was enhanced by soluble factors in serum from older men, but did not correlate with plasma lipid levels. Of the three subsets, intermediate monocytes formed the most foam cells.Therefore, both cellular changes to monocytes and soluble plasma factors in older men primes monocytes for foam cell formation following transendothelial migration, which may contribute to enhanced atherosclerosis in this population.",
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Ex vivo foam cell formation is enhanced in monocytes from older individuals by both extrinsic and intrinsic mechanisms. / Angelovich, Thomas A.; Shi, Margaret D.Y.; Zhou, Jingling; Maisa, Anna; Hearps, Anna C.; Jaworowski, Anthony.

In: Experimental Gerontology, Vol. 80, 01.07.2016, p. 17-26.

Research output: Contribution to journalArticleResearchpeer-review

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