Identification of Circulating Inflammatory Proteins Associated with Calcific Aortic Valve Stenosis by Multiplex Analysis

Rui Lin ¹, Yuexin Zhu ¹, Weiyao Chen ¹

⁰The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road, Chaoyang District, Beijing, 100029, China.

Cardiovascular Toxicology +

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April 8, 2024

View abstract on PubMed

Summary

Calcific aortic valve stenosis (CAVS) involves inflammation and calcification. Matrix metallopeptidase-1 (MMP1) and sirtuin 2 (SIRT2) proteins are causally linked to CAVS, offering potential therapeutic targets.

Area Of Science

Cardiovascular Biology
Inflammation Research
Proteomics

Background

Calcific aortic valve stenosis (CAVS) is a prevalent cause of mortality in aging populations.
It involves progressive inflammation and calcification of aortic valve leaflets.
Identifying key inflammatory proteins is crucial for therapeutic development.

Purpose Of The Study

To identify inflammatory proteins associated with CAVS occurrence and progression.
To investigate the causal relationship between these proteins and CAVS.
To explore potential therapeutic targets for CAVS.

Main Methods

Affinity-based proteomic assays to measure 92 inflammatory proteins.
Case-control cohort study to identify differential proteins.
Mendelian randomization using genome-wide association studies data (>400,000 individuals).
Single-cell and immunohistochemistry analysis for gene and protein expression.

Main Results

Five proteins showed significant positive correlation with CAVS severity.
Elevated matrix metallopeptidase-1 (MMP1) and sirtuin 2 (SIRT2) levels were causally associated with increased CAVS risk.
MMP1 and SIRT2 expression was significantly higher in calcified valves compared to controls.

Conclusions

MMP1 and SIRT2 are causally implicated in the pathogenesis of CAVS.
These proteins represent promising novel therapeutic targets for CAVS.
Further research into MMP1 and SIRT2 pathways could lead to effective treatments.

Keywords:

Calcific aortic valve stenosis Circulating inflammatory proteins Matrix metallopeptidase-1 Mendelian randomization Sirtuin 2