ATP depletion in macrophages in the core of advanced rabbit atherosclerotic plaques in vivo

Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH

“…Under hypoxia, cells switch to anaerobic metabolism, which leads to the production of lactate and thus the secretion of excess H + ions. Indeed, increased extracellular lactate concentrations are found particularly in the hypoxic areas of atherosclerotic lesions ( 14 ). Also, decreased extracellular pH values have been determined ( 15 ).…”

Intracellular ATP Decrease Mediates NLRP3 Inflammasome Activation upon Nigericin and Crystal Stimulation

“…Decreased iATP levels are also observed in several inflammatory situations. Among these are ischemia-reperfusion and atherosclerosis (27,28). Interestingly, in each of these experimental models, a parallel increase in IL-1b release was observed (4,29).…”

PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model

“…The combination of increased oxygen demand together with impaired oxygen diffusion capacity results in the presence of severe hypoxia (,1% oxygen) in macrophage-rich zones (150-300 mm) into the lesion (7-9). There is growing evidence that zones of hypoxia occur at depth in the atherosclerotic plaque (6,8). Leppanen et al (6) suggested that over time macrophages within the plaque core become adenosine triphosphate-depleted and severely hypoxic, contributing to their death and formation of a necrotic core that increases angiogenesis and plaque destabilization.…”

“…In the initial stages of atherogenesis, modified lipoproteins recruit monocytes and T cells. Macrophages internalize the modified lipoproteins, resulting in the accumulation of high-oxygenconsuming, high-metabolic-rate, lipid-loaded macrophages (foam cells) in developing lesions (5,6). The combination of increased oxygen demand together with impaired oxygen diffusion capacity results in the presence of severe hypoxia (,1% oxygen) in macrophage-rich zones (150-300 mm) into the lesion (7)(8)(9).…”

“…There is growing evidence that zones of hypoxia occur at depth in the atherosclerotic plaque (6,8). Leppanen et al (6) suggested that over time macrophages within the plaque core become adenosine triphosphate-depleted and severely hypoxic, contributing to their death and formation of a necrotic core that increases angiogenesis and plaque destabilization. Sluimer et al (9) demonstrated the direct presence of hypoxia in the macrophage-rich regions of advanced human carotid atherosclerotic plaques using the hypoxia marker pimonidazole, correlating hypoxia with CD68-positive macrophages, and angiogenesis.…”