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BMP6, a potential biomarker of inflammatory fibrosis and promising protective factor for dilated cardiomyopathy
Feng Jiang1, Jiayang Tang1, Xiaoqi Wei1
1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, China.
Insights
Bone morphogenetic protein 6 (BMP6) is a promising biomarker for dilated cardiomyopathy (DCM) and a potential therapeutic target due to its antifibrotic effects in heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Fibrosis Research
Background:
- Dilated cardiomyopathy (DCM) is a major cause of heart failure, exacerbated by inflammation and aging.
- Cardiac fibrosis is a key driver of adverse remodeling in DCM-induced heart failure.
- Understanding the molecular mechanisms underlying DCM progression is crucial for developing effective treatments.
Purpose of the Study:
- To identify specific biomarkers and therapeutic targets for DCM-induced heart failure.
- To investigate the role of BMP6 in the context of DCM and cardiac fibrosis.
- To validate BMP6 as a potential diagnostic and therapeutic agent.
Main Methods:
- Utilized bulk and single-cell RNA sequencing (RNA-seq) to analyze DCM heart tissue.
- Employed Mendelian randomization analysis to establish causality.
- Constructed animal models and performed BMP6 knockdown experiments.
Main Results:
- DCM hearts showed significant inflammatory cell infiltration and fibrosis.
- Aberrant BMP6 expression was identified in fibroblasts of DCM hearts.
- BMP6 demonstrated high specificity as a biomarker for DCM and a protective role against it.
- BMP6 knockdown increased collagen production, confirming its antifibrotic function.
Conclusions:
- BMP6 is a potential diagnostic biomarker for DCM.
- BMP6 exhibits antifibrotic properties, making it a promising therapeutic target for DCM-induced heart failure.
- Further research into BMP6 modulation could lead to novel heart failure treatments.
Background:
Dilated cardiomyopathy (DCM) stands as one of the most prevalent and severe causes of heart failure. Inflammation plays a pivotal role throughout the progression of DCM to heart failure, while age acts as a natural predisposing factor for all cardiovascular diseases. These two factors often interact, contributing to cardiac fibrosis, which is both a common manifestation and a pathogenic driver of adverse remodeling in DCM-induced heart failure.
Method:
Bulk RNA-seq, single-cell RNA-seq, Mendelian randomization analysis, animal model construction, and BMP6 knockdown were utilized to identify and validate potential specific markers and targets for intervention in DCM heart failure.
Results:
We found that DCM hearts exhibit pronounced inflammatory cell infiltration and fibrosis. Both bulk RNA-seq and single-cell RNA-seq analyses revealed aberrant BMP6 expression specifically in fibroblasts. The ROC curve underscores the high specificity of BMP6 in relation to DCM, while Mendelian randomization analysis further confirms BMP6 as a protective factor against DCM. Notably, BMP6 knockdown led to a decrease in SMAD6 expression and a marked elevation in COL1A1 expression levels, indicating its antifibrotic role.
Conclusion:
BMP6 emerges as a promising biomarker for DCM, and its functional role in exerting an antifibrotic effect underscores its potential as a therapeutic target.
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