Soluble CD146 in Heart Failure: Pathophysiological Role and Diagnostic Potential
Abstract
:1. Introduction
2. CD146: Structure, Expression, and Regulation
2.1. Molecular Structure
2.2. Expression Profile
2.3. Isoforms of CD146
2.4. Regulation of CD146 Expression and Shedding
3. Pathophysiological Role of CD146 in Heart Failure: Mechanisms and Vascular Implications
3.1. Hemodynamic Stress and Endothelial Activation
3.2. Inflammatory Cytokines and Oxidative Stress
3.3. CD146 and Endothelial Dysfunction: Amplifying Congestion
4. Clinical Relevance and Diagnostic Studies
4.1. Diagnostic Value in Acute and Chronic Heart Failure
4.2. Associations with Imaging and Hemodynamic Parameters
4.3. Complementarity to Established Biomarkers
5. CD146 and Traditional Biomarkers in Heart Failure
5.1. Comparative Analysis: CD146 vs. Traditional Biomarkers in Heart Failure
5.2. Diagnostic Utility of Integrated Biomarker Panels in Heart Failure
6. Limitations and Confounding Conditions
sCD146 and Renal Dysfunction
7. Therapeutic Prospects of Targeting CD146 in Heart Failure
- Neutralization of sCD146 is an alternative approach. The monoclonal antibody M2J-1, developed to specifically bind sCD146 while sparing the membrane-bound form, has shown efficacy in preclinical cancer models, reducing pathological angiogenesis and inflammation without compromising vascular stability [38,69]. This targeted strategy may have relevance in HF, especially in HFpEF, where persistent congestion and endothelial inflammation are key drivers of disease [14,19].
- Direct blockade of endothelial CD146 has also been explored. In neuroinflammation models, the monoclonal antibody AA98 reduced leukocyte extravasation and tissue injury by disrupting CD146-mediated immune cell adhesion [36,70]. Translating this concept to HF could help modulate chronic inflammatory infiltration in the myocardium and peripheral organs, though careful dosing would be needed to avoid impairing normal immune function.
8. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
HF | Heart failure |
NYHA | New York Heart Association |
RAAS | Renin–angiotensin–aldosterone system |
SNS | Sympathetic nervous system |
ADH | Antidiuretic hormone |
NO | Antidiuretic hormone |
ROS | Reactive oxygen species |
CKD | Chronic kidney disease |
lgCD146 | long form CD146 |
shCD146 | short form CD146 |
sCD146 | soluble form CD146 |
MMP | Matrix metalloproteinases |
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Application | Details |
---|---|
Diagnostic Utility | Elevated sCD146 levels are associated with systemic and pulmonary congestion, reflecting endothelial dysfunction and vascular strain. It complements traditional biomarkers like NT-proBNP in diagnosing HF. |
Prognostic Value | High sCD146 levels predict adverse outcomes, including rehospitalization, disease progression, and mortality. It provides independent prognostic information, especially in conjunction with other biomarkers. |
Monitoring Therapy | Serial measurements of sCD146 can be used to monitor treatment response, especially in decongestive therapy. Reductions in sCD146 levels may indicate effective decongestion and improved endothelial function. |
Utility in HF with Preserved Ejection Fraction (HFpEF) | sCD146 is valuable in diagnosing and monitoring HFpEF, where traditional markers like NT-proBNP may be less reliable. |
Identification of Subclinical Congestion | Persistent elevation of sCD146 levels may indicate residual congestion even after apparent clinical improvement, identifying patients at risk for relapse. |
Biomarker | Source | Primary Signal | Clinical Strengths | Limitations |
---|---|---|---|---|
NT-proBNP | Cardiomyocytes | Myocardial wall stretch | High sensitivity for volume overload; prognosis | Affected by renal function, obesity |
Troponin I/T | Cardiomyocytes | Myocyte necrosis | Acute coronary syndrome, myocardial injury | Does not reflect congestion |
Galectin-3 | Fibroblasts | Fibrosis, inflammation | Risk stratification | Low specificity |
sST2 | Immune cells, myocardium | Cardiac stress, inflammation | Prognosis | Influenced by comorbidities |
sCD146 | Endothelial cells | Endothelial dysfunction, congestion | Complements NT-proBNP; reflects vascular strain and central congestion | Elevated in malignancy, inflammatory diseases; limited outcome data |
Syndecan-1 | Endothelial glycocalyx | Glycocalyx degradation, microvascular damage | Independent predictor of early mortality, reflects systemic endothelial injury | Elevated in other critical illnesses (e.g., sepsis); lacks cardiac specificity |
Endocan | Activated endothelial cells | Endothelial inflammation and dysfunction | Elevated in cardiogenic shock; correlates with BNP and disease severity | Prognostic role in HF still emerging; not specific to HF |
VCAM-1 | Cytokine-activated endothelium | Leukocyte adhesion and inflammation | Reflects cytokine-driven endothelial inflammation; part of the acute HF inflammatory profile | Prognostic power unclear in acute HF; overlap with CRP and other inflammatory markers |
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Mocan, D.; Jipa, R.; Jipa, D.A.; Lala, R.I.; Puschita, M.; Rasinar, F.-C.; Balta, D.-F.; Groza, I.-S.; Uzum, A. Soluble CD146 in Heart Failure: Pathophysiological Role and Diagnostic Potential. Biomedicines 2025, 13, 1370. https://doi.org/10.3390/biomedicines13061370
Mocan D, Jipa R, Jipa DA, Lala RI, Puschita M, Rasinar F-C, Balta D-F, Groza I-S, Uzum A. Soluble CD146 in Heart Failure: Pathophysiological Role and Diagnostic Potential. Biomedicines. 2025; 13(6):1370. https://doi.org/10.3390/biomedicines13061370
Chicago/Turabian StyleMocan, Daniela, Radu Jipa, Daniel Alexandru Jipa, Radu Ioan Lala, Maria Puschita, Florin-Claudiu Rasinar, Diana-Federica Balta, Iulia-Silvia Groza, and Amelia Uzum. 2025. "Soluble CD146 in Heart Failure: Pathophysiological Role and Diagnostic Potential" Biomedicines 13, no. 6: 1370. https://doi.org/10.3390/biomedicines13061370
APA StyleMocan, D., Jipa, R., Jipa, D. A., Lala, R. I., Puschita, M., Rasinar, F.-C., Balta, D.-F., Groza, I.-S., & Uzum, A. (2025). Soluble CD146 in Heart Failure: Pathophysiological Role and Diagnostic Potential. Biomedicines, 13(6), 1370. https://doi.org/10.3390/biomedicines13061370