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Presence of oxidized low density lipoprotein in nonrheumatic stenotic aortic valves
M Olsson1, J Thyberg, J Nilsson
1Department of Cardiology, Karolinska Hospital, Stockholm, Sweden. margareta.olsson@medks.ki.se
Insights
Oxidized low-density lipoprotein (LDL) particles accumulate in diseased aortic valves, alongside immune cells and calcium. This suggests oxidized lipids may contribute to the progression of aortic stenosis.
Area of Science:
- Cardiovascular Biology
- Immunology
- Pathology
Background:
- Degenerative aortic stenosis is a prevalent condition in the elderly, characterized by inflammation.
- The precise mechanisms driving degenerative aortic stenosis remain unclear.
- Aortic valve disease shares inflammatory similarities with atherosclerosis.
Purpose of the Study:
- To investigate the presence and significance of oxidized low-density lipoprotein (LDL) particles within stenotic aortic valve tissue.
- To explore the relationship between oxidized lipids, inflammation, and calcification in aortic stenosis.
Main Methods:
- Immunohistochemistry was used to detect apoB, 4-hydroxynonenal-modified LDL, leukocytes, and HLA-DR in stenotic and control aortic valves.
- Oil red O staining identified neutral lipids.
- Comparison of six stenotic valves with three control valves.
Main Results:
- Stenotic valves showed extracellular neutral lipid accumulation colocalizing with apoB and oxidized LDL.
- Oxidized LDL was found around calcium deposits, subendothelially, and in the fibrosa layer.
- Oxidized LDL colocalized with macrophages, T lymphocytes, and HLA-DR, indicating an inflammatory response. Control valves lacked significant inflammation.
Conclusions:
- Oxidized LDL particles are present in stenotic aortic valve tissue.
- The colocalization of oxidized LDLs with immune cells and calcium suggests a role in the pathogenesis of aortic stenosis.
- These findings highlight potential therapeutic targets for aortic valve disease.
Abstract:
The aim of the present study was to analyze if LDL particles trapped in stenotic aortic valve tissue undergo oxidative modification. Degenerative aortic stenosis affects >3% of the population >75 years of age in the Western world. Recent studies have revealed the presence of a chronic inflammatory process similar to what has been described in other degenerative diseases such as atherosclerosis. However, the underlying disease mechanisms of degenerative aortic stenosis still remain largely unknown. Six tricuspid stenotic valves, obtained at valve replacement, were compared with 3 control valves collected from hearts taken out during transplantation. The stenotic valves and the control valves were examined by immunohistochemistry, using antibodies against apoB, 4-hydroxynonenal-modified LDL, leukocytes, and HLA-DR. All valves were also stained with oil red O for neutral lipids. Extracellular neutral lipids were found in all stenotic valves, extending from the bases along the fibrosa layer. This lipid colocalized with apoB- and 4-hydroxynonenal-modified LDL immunoreactivity. 4-Hydroxynonenal-modified LDLs were present around calcium deposits, subendothelially, and in the deeper layer of the fibrosa. There was also a colocalization with macrophages, T lymphocytes, and HLA-DR expression. Control valves had a thin area of neutral lipid accumulation, a small amount of apoB, but no signs of inflammation. A distinct colocalization between oxidized LDLs, T-lymphocyte accumulation, and calcium deposits suggests that oxidized lipids may play a role in the disease process.