Aortic stenosis (AS) is a disease characterized by narrowing of the aortic valve (AV)
orifice. The purpose of this study was to clarify the significance of bacterial detection
and clinicopathological factors, including valve-infiltrating immune cells and disease
severity, in relation to AS. After obtaining the written informed consent form from
50 patients with AS, we performed immunohistochemical analysis of lipopolysaccharide
(LPS) for gram-negative bacteria and lipoteichoic acid (LTA) for gram-positive bacteria
on surgically resected-AVs. Moreover, we evaluated the relationships among the presence
of bacteria, immune checkpoint protein PD-L1 expression, and immune cell infiltrations
such as CD8-positive T lymphocytes, CD163-positive macrophages, and FOXP3-positive
regulatory T cell (Treg) in resected-aortic valves. LPS detection in the resected-aortic
valve tissues was significantly associated with stromal PD-L1 expression, valve calcification,
and LTA existence in resected samples. We showed that the presence of LPS was significantly
related to high PD-L1 expression only in calcified-AVs, not in non-calcified-AVs.
Moreover, the high expression of PD-L1 in AS samples without LPS was significantly
associated with positive infiltration of CD163-positive macrophages and FOXP3-positive
Tregs. Immunohistochemical bacterial detection in resected-aortic valves was associated
with PD-L1 accumulation and valve calcification. PD-L1 significantly accumulated only
in calcified valves with LPS existence.
Graphical abstract
Graphical Abstract
Keywords
Abbreviations:
AS (aortic valve stenosis), AV (aortic valve), LPS (lipopolysaccharide), LTA (lipoteichoic acid), PD-L1 (programmed death ligand 1), CD8 (cluster of differentiation 8), CD163 (cluster of differentiation 163), FOXP3 (forkhead box protein 3), ICI (immune checkpoint inhibitor), VIC (valvular interstitial cell)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: October 21, 2021
Footnotes
Ethics approval and consent to participate: This study conformed to the Declaration of Helsinki and was approved by the Institutional Review Board of the Clinical Research at Gunma University Hospital (approval number: HS2020-014, May 19, 2020). Informed consent for this retrospective study was obtained by the opt-out method.
Funding: This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS); grant numbers 19K18171.
Conflicts of Interest: The authors have no conflicts of interest to disclose.
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- Commentary: Are Explanted Aortic Valves Always Infected?Seminars in Thoracic and Cardiovascular SurgeryVol. 34Issue 4
- PreviewAtherosclerosis and aortic valve stenosis (AS) are considered part of a single pathological process. Previous work focused on the relationships between inflammatory markers like C-reactive protein, tumor necrosis factor alpha (TNF-α) interleukin-6 (IL-6) and the progression of AS.1 Other studies investigated the association between bacteria and viruses and AS2,3 because the pathogenic mechanisms of age-related calcific AS are still not fully understood although endothelial damage lies always beneath.
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- PreviewSenile aortic stenosis has been associated with chronic inflammatory immune response initiated by the presence of gram-negative bacteria.1 This response leads to the osteogenic calcification of aortic valve leaflets, however, there has been so far no clear evidence of the presence of these bacteria and their association with the progression of the aortic stenosis. In this context, Erkhem-Ochir and colleagues2 found a strong association between gram-negative bacteria and high expression of programmed cell death-1 ligand and immune-cell-induced inflammation in patients with aortic stenosis.
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