Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage

Abstract

Visual Abstract

Parallel Murine and Human Plaque Proteomics Reveals Pathways of Plaque Rupture

“…Absence of these proteins would limit comparison of our data with proteomic data generated by others using different extraction methods. 25 , 26 In addition, because the murine and human data exhibit only modest overlap in altered expression of individual proteins, our data suggest important differences between the biochemistry of SR-uPA +/0 aortas and human carotid plaques. For example, the proteases that are more abundant in SR-uPA +/0 aortas (MMP2 and MMP3) differ from the proteases that are more abundant in ruptured human plaques (MMP9, MMP12, MMP19, neutrophil elastase, Cathepsins B, D, G, and Z, chymase, carboxypeptidase B2, carboxypeptidase N, and mast cell carboxypeptidase).…”

“… 24 Identification of these pathways could provide new drug targets and could also reveal markers of unstable atherosclerosis. 25 , 26 …”

Internal Bleeding

“…The observations of Matic et al. (1) raise a number of interesting questions that merit further investigation. Is intraplaque hemorrhage a characteristic of carotid atheromata, or does it affect atherosclerotic plaques in other vascular beds?…”

“…In this issue of JACC: Basic to Translational Science , Matic et al. (1) report transcriptomic and proteomic profiling of atherosclerotic plaques banked from carotid endarterectomies. In parallel, they looked at blood sampled near the lesion in vivo in comparison to peripheral blood.…”

“…Matic et al. (1) found that exposure to ferric iron was associated with iron uptake by THP-1 human monocyte cell line–derived macrophage-like cells and stimulated HMOX1 and BLVRB expression, suggesting that local hemolysis and iron derived from heme drive the elevated concentrations of these enzymes in plaques. Intraplaque hemorrhage promotes erythrocyte sequestration and localized hemolysis, hemostasis, and coagulation, including platelet activation, fibrin formation, and trapping of leukocytes, mainly neutrophils, in human plaques (2) .…”