Apolipoproteins B, (a), and E Accumulate in the Morphologically Early Lesion of ‘Degenerative’ Valvular Aortic Stenosis

TLDR

Nonrheumatic aortic stenosis of trileaflet valves, traditionally viewed as degenerative, actually harbors chronic inflammatory cells such as macrophages and T lymphocytes in its early lesions. The study aimed to determine whether lipoproteins accumulate in aortic valve lesions. Immunohistochemistry on 18 trileaflet aortic valves ranging from normal to stenotic was used to detect apolipoproteins B, (a), E, macrophages, and α‑actin–expressing cells. All three apolipoproteins were present in lesions from early to end‑stage but absent in normal valves, and most extracellular valve lipid co‑localized with these apolipoproteins, supporting the idea that lipoprotein accumulation drives aortic stenosis pathogenesis.

Abstract

Abstract Nonrheumatic aortic stenosis of trileaflet aortic valves has been considered to be a “degenerative” process, but the early lesion of aortic stenosis contains the chronic inflammatory cells, macrophages and T lymphocytes. Because lipoprotein deposition is prominent in atherosclerosis, another chronic inflammatory process, this study examined whether lipoproteins accumulate in aortic valve lesions. Immunohistochemical studies were performed to detect apolipoprotein (apo) B, apo(a), apoE, macrophages, and α-actin–expressing cells on 18 trileaflet aortic valves that ranged from normal to stenotic. All three apolipoproteins were detected in early through end-stage lesions of aortic stenosis but not in histologically normal regions. Comparison with oil red O staining suggested that most of the extracellular neutral lipid in these valves was associated with either plasma-derived or locally produced apolipoproteins. Thus, in early through end-stage aortic valve lesions, apolipoproteins accumulate and are associated with the majority of extracellular valve lipid. These results are consistent with the hypothesis that lipoprotein accumulation in the aortic valve contributes to pathogenesis of aortic stenosis.