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Valvular Prostaglandins Are Elevated in Severe Human Aortic Valve Stenosis
Lucien G J Cayer1,2, Arun Surendran3,4, Tobias Karakach1,5
1Food and Human Nutritional Sciences (L.G.J.C., T.K., H.M.A.), University of Manitoba, Winnipeg, Canada.
Insights
Oxylipins, particularly those from the arachidonic acid-COX pathway, are significantly elevated in aortic valve stenosis (AVS). This finding suggests potential therapeutic targets for slowing AVS progression.
Area of Science:
- Cardiovascular Medicine
- Lipidomics
- Biochemistry
Background:
- Aortic valve stenosis (AVS) is a prevalent valvular heart disease characterized by valve remodeling, leading to heart failure.
- Current therapeutic strategies for AVS lack pharmacological interventions to slow disease progression.
- Emerging evidence suggests a potential role for oxylipins in the pathogenesis of AVS.
Purpose of the Study:
- To investigate the role of oxylipins in the human aortic valve (AV) and plasma of patients with AVS.
- To identify specific oxylipin pathways associated with AVS severity.
- To explore potential therapeutic targets for AVS based on oxylipin dysregulation.
Main Methods:
- Targeted oxylipin analysis using high-performance liquid chromatography-tandem mass spectrometry.
- Analysis of human AV tissue and plasma samples from 110 patients undergoing AV surgery.
- Comparison of oxylipin profiles in patients with varying AVS severity and with healthy controls.
Main Results:
- 36 oxylipins were identified in human AV tissue, with all showing increased levels in severe AVS.
- The arachidonic acid-COX (cyclooxygenase) pathway-derived prostanoids were most associated with AVS severity.
- Distinct oxylipin profiles were observed between AVS patients and healthy controls in plasma samples.
Conclusions:
- Oxylipins, specifically prostanoids involved in inflammation and osteogenesis, are positively correlated with AVS severity.
- The identified prostanoid dysregulation highlights cyclooxygenase (COX) inhibition as a potential therapeutic strategy for AVS.
- Further research is warranted to explore the therapeutic efficacy of COX inhibition in mitigating AVS.
Background:
Aortic valve stenosis (AVS) is the most common valvular disease in the developed world. AVS involves the progressive fibrocalcific remodeling of the aortic valve (AV), which impairs function and can ultimately lead to heart failure. Due to gaps in our understanding of the underlying mechanisms of AVS, there are no pharmacological treatments or dietary interventions known to slow AVS progression. Recent studies have begun to suggest oxylipins-a class of bioactive lipids-may be dysregulated in the valves of patients with AVS.
Methods:
We utilized high-performance liquid chromatography-tandem mass spectrometry to conduct a targeted oxylipin analysis on human AV tissue and plasma from a cohort of 110 patients undergoing AV surgery.
Results:
We identified 36 oxylipins in human AV tissue with all showing significant increase in patients with severe AVS. A multivariate model including patient characteristics and valvular oxylipins identified the arachidonic acid-COX (cyclooxygenase) pathway-derived prostanoids to be the most associated with AVS severity. Plasma oxylipin levels were measured in a subset of AV surgery patients and compared with a control group of healthy participants, showing distinct oxylipin profiles between control and disease.
Conclusions:
Our comprehensive analysis of oxylipins in the human AV identified the inflammatory and osteogenic regulating prostanoids to be positively correlated with AVS severity. This elucidation of prostanoid dysregulation warrants further research into COX inhibition to mitigate AVS.
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