Genetic and Pharmacological Inhibition of TREM-1 Limits the Development of Experimental Atherosclerosis

Abstract

We identified TREM-1 as a major upstream proatherogenic receptor. We propose that TREM-1 activation orchestrates monocyte/macrophage proinflammatory responses and foam cell formation through coordinated and combined activation of CD36 and TLR4. Blockade of TREM-1 signaling may constitute an attractive novel and double-hit approach for the treatment of atherosclerosis.

Prognostic Utility of Soluble TREM‐1 in Predicting Mortality and Cardiovascular Events in Patients With Acute Myocardial Infarction

“…Recently, studies reported that TREM‐1 contributes to the development of atherosclerosis through promoting monocytosis, monocyte/macrophage proinflammatory responses, and formation of inflammatory foam cells 23, 24. TREM‐1 gene polymorphisms are significantly associated with higher coronary atherosclerosis severity in a Russian population 25.…”

Genetic Depletion or Hyperresponsiveness of Natural Killer Cells Do Not Affect Atherosclerosis Development

“…Plasma cholesterol was measured using a commercial kit (DiaSys® Cholesterol FS*, Germany). Quantification of lesion size and composition was performed as previously described 29 . Briefly, the heart and ascending aorta were removed, perfusion-fixed in situ with 4% paraformaldehyde, then placed in phosphate-buffered saline (PBS)-30% sucrose solution overnight, before being embedded in frozen optimal cutting temperature compound and frozen at -70°C.…”

“…Lipids were detected using Oil Red O (Sigma-Aldrich, St. Louis, Missouri) coloration and quantified by a blinded operator using HistoLab software (Microvisions Instruments, Paris, France) 30 , which was also used for morphometric studies. En face quantification was used for atherosclerotic plaques along thoraco-abdominal aorta, as previously described 29 .…”

TREML4 Promotes Inflammatory Programs in Human and Murine Macrophages and Alters Atherosclerosis Lesion Composition in the Apolipoprotein E Deficient Mouse

“…In fact, most members of the TREM receptor family have been implicated in either the preceding inflammatory state or directly in the pathogenesis of atherosclerosis disease in both humans and mice (14)(15)(16)(17). For example, TREM1 is upregulated in dyslipidemia and promotes atherosclerosis by inducing monocytosis and foam cell formation in both humans and mice (16,18). Furthermore, circulating soluble TREML1, which modulates platelet-endothelial cell interactions and sepsis progression (19), also positively correlates with clinical presentation of acute coronary syndrome (14).…”