Ferryl hemoglobin and heme induce Α1‐microglobulin in hemorrhaged atherosclerotic lesions with inhibitory function against hemoglobin and lipid oxidation

Dávid Pethő, Tamás Gáll, Zoltán Hendrik, Annamária Nagy, Lívia Beke, Attila Péter Gergely, Gábor Méhes, Csaba Tóth, Magnus Gram, Bo Åkerström, György Balla, József Balla

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Infiltration of red blood cells into atheromatous plaques and oxidation of hemoglobin (Hb) and lipoproteins are implicated in the pathogenesis of atherosclerosis. α1‐microglobulin (A1M) is a radical‐scavenging and heme‐binding protein. In this work, we examined the origin and role of A1M in human atherosclerotic lesions. Using immunohistochemistry, we observed a significant A1M immunoreactivity in atheromas and hemorrhaged plaques of carotid arteries in smooth muscle cells (SMCs) and macrophages. The most prominent expression was detected in macrophages of organized hemorrhage. To reveal a possible inducer of A1M expression in ruptured lesions, we exposed aortic endothelial cells (ECs), SMCs and macrophages to heme, Oxy‐ and FerrylHb. Both heme and FerrylHb, but not OxyHb, upregulated A1M mRNA expression in all cell types. Importantly, only FerrylHb induced A1M protein secretion in aortic ECs, SMCs and macrophages. To assess the possible function of A1M in ruptured lesions, we analyzed Hb oxidation and heme‐catalyzed lipid peroxidation in the presence of A1M. We showed that recombinant A1M markedly inhibited Hb oxidation and heme‐driven oxidative modification of low‐density lipoproteins as well plaque lipids derived from atheromas. These results demonstrate the presence of A1M in atherosclerotic plaques and suggest its induction by heme and FerrylHb in the resident cells.

Originalspråkengelska
Artikelnummer6668
TidskriftInternational Journal of Molecular Sciences
Volym22
Utgåva13
DOI
StatusPublished - 2021

Ämnesklassifikation (UKÄ)

  • Kardiologi

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