Diverse Bacteria Promote Macrophage Foam Cell Formation Via Toll-Like Receptor-Dependent Lipid Body Biosynthesis

Nicolaou, Giovanna; Goodall, Alison H.; Erridge, Clett

doi:10.5551/jat.10249

Cited by 51 publications

(50 citation statements)

References 48 publications

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“…TLR1/2 and TLR4 agonists stimulate lipid body formation in the presence and absence of lipoprotein supplementation (33). The ability of TLR agonists to prolong TAG retention, in addition to augmenting the uptake of oxidized LDL (and promoting desmosterol synthesis (34)), suggests that both phenomena may contribute to the formation of macrophage foam cells in vivo.…”

Section: Discussionmentioning

confidence: 99%

Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in Macrophages

Huang¹,

Morales‐Rosado²,

Ray³

et al. 2014

Journal of Biological Chemistry

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Background: How microbial agonists induce macrophages to store triglycerides (TAG) for prolonged periods was not known. Results: Toll-like receptor (TLR)1/2, TLR3, and TLR4 agonists increased fatty acid uptake, increased TAG synthesis, and decreased lipolysis, augmenting TAG storage for Ն72 h. Conclusion: TAG retention is an active, multifaceted, and long lasting response to sensing microbes. Significance: Prolonged TAG storage contributes to foam cell formation.

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Section: Discussionmentioning

confidence: 99%

Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in Macrophages

Huang¹,

Morales‐Rosado²,

Ray³

et al. 2014

Journal of Biological Chemistry

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“…Diverse bacteria promote formation of foam cells from macrophages by lipid body biosynthesis that is dependent upon toll-like receptors (226). In this study, foam cell formation cannot be caused by phagocytosis of oxidized LDL by the scavenger receptor, since neither inhibition of LDL oxidation nor inhibition of the scavenger receptor are able to prevent foam cell formation by bacteria.…”

Section: Homocysteine Inflammation Infection and Atherogenesismentioning

confidence: 75%

Homocysteine Metabolism, Atherosclerosis, and Diseases of Aging

McCully

2015

Comprehensive Physiology

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The importance of homocysteine in vascular function and arteriosclerosis was discovered by demonstration of arteriosclerotic plaques in children with homocystinuria caused by inherited enzymatic deficiencies of cystathionine synthase, methionine synthase, or methylene-tetrahydrofolate reductase. According to the homocysteine theory of arteriosclerosis, an elevated blood homocysteine level is an important risk factor for atherosclerosis in subjects without these rare enzymatic abnormalities. The homocysteine theory is supported by demonstration of arterial plaques in experimental animals with hyperhomocysteinemia, by discovery of a pathway for conversion of homocysteine thiolactone to sulfate in cell cultures from children with homocystinuria, and by demonstration of growth promotion by homocysteic acid in normal and hypophysectomized animals. Studies with cultured malignant cells revealed abnormal homocysteine thiolactone metabolism, resulting in homocysteinylation of proteins, nucleic acids, and glycosaminoglycans, explaining the abnormal oxidative metabolism, abnormalities of cellular membranes, and altered genetic expression observed in malignancy. Abnormal homocysteine metabolism in malignant cells is attributed to deficiency of thioretinamide, the amide synthesized from retinoic acid and homocysteine thiolactone. Two molecules of thioretinamide combine with cobalamin to form thioretinaco. Based on the molecular structure of thioretinaco, a theory of oxidative phosphorylation was proposed, involving oxidation to a disulfonium derivative by ozone, and binding of oxygen, nicotinamide adenine dinucleotide and phosphate as the active site of adenosine triphosphate synthesis in mitochondria. Obstruction of vasa vasorum by aggregates of microorganisms with homocysteinylated low-density lipoproteins is proposed to cause ischemia of arterial wall and a microabscess of the intima, the vulnerable atherosclerotic plaque.

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“…A recent study found that exposure to a wide variety of bacteria commonly found in human atherosclerotic plaques induced lipid body formation and cholesterol ester accumulation in murine macrophages. 119 Furthermore, this effect was found to occur in a Toll-like receptor (TLR) 2 and/or TLR 4 dependent manner, giving rise to the possibility that debris from non-viable bacteria within macrophages may promote foam cell formation by interacting with TLRs. Thus exposure to the microbial components of respiratory pathogens may provide a more extreme example of the microbial priming for plaque progression provided by the oral and gut commensals.…”

Section: Localised Vascular Inflammationmentioning

confidence: 97%

“…119 Aside from potential direct infection of plaques, the finding of bacterial debris in human plaques may be the result of recruitment to the plaque of inflammatory cells that have already encountered micro-organisms in the lung or other remote locations, leading to increased localised inflammation and atherosclerosis progression. A recent study found that exposure to a wide variety of bacteria commonly found in human atherosclerotic plaques induced lipid body formation and cholesterol ester accumulation in murine macrophages.…”

Section: Localised Vascular Inflammationmentioning

confidence: 99%

Mechanistic links between acute respiratory tract infections and acute coronary syndromes

Bazaz¹,

Marriott²,

Francis³

et al. 2013

Journal of Infection

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Diverse Bacteria Promote Macrophage Foam Cell Formation Via Toll-Like Receptor-Dependent Lipid Body Biosynthesis

Abstract: Conclusions:The bacterial debris observed in human atheroma, which is currently considered to be harmless, may have potential to contribute to disease progression via TLR-dependent lipid body formation in macrophages.

Cited by 51 publications

References 48 publications

Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in Macrophages

Toll-like Receptor Agonists Promote Prolonged Triglyceride Storage in Macrophages

Homocysteine Metabolism, Atherosclerosis, and Diseases of Aging

Mechanistic links between acute respiratory tract infections and acute coronary syndromes

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