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Lim Domain Binding 3 (Ldb3) Identified as a Potential Marker of Cardiac Extracellular Vesicles
Fadi Abou Zeid1, Henri Charrier1, Olivia Beseme1
1U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, Institut Pasteur de Lille, Université de Lille, Inserm, CHU Lille, 59000 Lille, France.
Insights
Researchers identified Ldb3 as a potential biomarker for cardiac extracellular vesicles (EVs). This discovery could aid in diagnosing heart conditions by improving the isolation and analysis of EVs derived from the heart.
Area of Science:
- Cardiovascular Biology
- Extracellular Vesicle Research
- Biomarker Discovery
Background:
- Extracellular vesicles (EVs) are crucial for cell communication and hold potential as biomarkers for cardiac diseases.
- Current limitations in identifying cardiac-specific EVs hinder understanding their role in heart function and disease.
- Lack of specific markers restricts the isolation and analysis of cardiac EVs.
Purpose of the Study:
- To identify specific protein markers for cardiac extracellular vesicles (EVs).
- To validate the presence and origin of identified markers in cardiac EVs.
- To explore the potential of these markers in diagnosing cardiac conditions.
Main Methods:
- Proteomic analysis of EVs isolated from rat cardiomyocytes, cardiac fibroblasts, cardiac tissue, and plasma using ultracentrifugation and EVtrap.
- Validation of marker enrichment using diverse EV isolation techniques.
- Comparative analysis of marker expression in different rat tissues and cell types.
- Assessment of marker levels in heart tissue and EVs from heart failure patients.
Main Results:
- Ldb3, a Z-disc cytoskeletal protein, was identified as enriched in cardiac EVs.
- Ldb3 was found in both small and large EVs across different isolation methods.
- Ldb3 expression was predominantly observed in the neonatal rat heart, specifically in cardiomyocytes.
- Decreased Ldb3 levels were noted in the left ventricle of heart failure patients, but not in their EVs.
Conclusions:
- Ldb3 is a promising candidate marker for cardiomyocytes-derived EVs.
- Ldb3 has the potential to facilitate the identification of cardiac EVs in various physiological and pathological states.
- This finding may advance the diagnostic capabilities for heart diseases through EV analysis.
Abstract:
Extracellular vesicles (EVs) are considered as transporters of biomarkers for the diagnosis of cardiac diseases, playing an important role in cell-to-cell communication during physiological and pathological processes. However, specific markers for the isolation and analysis of cardiac EVs are missing, imposing limitation on understanding their function in heart tissue. For this, we performed multiple proteomic approaches to compare EVs isolated from neonate rat cardiomyocytes and cardiac fibroblasts by ultracentrifugation, as well as EVs isolated from minced cardiac tissue and plasma by EVtrap. We identified Ldb3, a cytoskeletal protein which is essential in maintaining Z-disc structural integrity, as enriched in cardiac EVs. This result was validated using different EV isolation techniques showing Ldb3 in both large and small EVs. In parallel, we showed that Ldb3 is almost exclusively detected in the neonate rat heart when compared to other tissues, and specifically in cardiomyocytes compared to cardiac fibroblasts. Furthermore, Ldb3 levels, specifically higher molecular weight isoforms, were decreased in the left ventricle of ischemic heart failure patients compared to control groups, but not in the corresponding EVs. Our results suggest that Ldb3 could be a potential cardiomyocytes derived-EV marker and could be useful to identify cardiac EVs in physiological and pathological conditions.
