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Monocyte chemoattractant protein 1 (MCP-1) gene expression in dilated cardiomyopathy
M H Lehmann1, H Kühnert, S Müller
1Department of Internal Medicine, Division of Cardiology, University of Jena, Jena, Germany.
Insights
Monocyte chemoattractant protein 1 (MCP-1) levels correlate with left ventricular dysfunction severity in dilated cardiomyopathy (DCM). Higher MCP-1 expression and protein indicate increased inflammation and potential myocyte damage in severe DCM.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Leukocyte-mediated cytotoxicity is implicated in cardiac myocyte damage in chronic myocarditis and dilated cardiomyopathy (DCM).
- Chemokines, such as monocyte chemoattractant protein 1 (MCP-1), regulate leukocyte migration and tissue infiltration.
- Previous studies detected MCP-1 messenger RNA in DCM endomyocardial biopsy tissues, suggesting its role in leukocyte recruitment and cardiomyocyte damage.
Purpose of the Study:
- To investigate the association between the severity of left ventricular dysfunction in DCM and quantitative changes in MCP-1 messenger RNA and protein levels in endomyocardial biopsy tissue.
- To determine if MCP-1 expression correlates with the degree of cardiac damage and inflammatory cell infiltration in DCM patients.
Main Methods:
- Quantitative polymerase chain reaction was used to measure MCP-1 messenger RNA expression.
- Immunohistochemistry was employed to detect MCP-1 protein and infiltrating inflammatory cells.
- Endomyocardial biopsy tissues from DCM patients with varying degrees of left ventricular dysfunction (ejection fraction) were analyzed.
Main Results:
- DCM patients with severe left ventricular dysfunction (lower ejection fraction) exhibited significantly higher MCP-1 messenger RNA expression (2.35-fold increase) compared to those with less severe dysfunction (P=0.0229).
- MCP-1 protein was detected in all severe DCM cases, predominantly in the cardiac interstitium, and in a patchy pattern near intramyocardial vessels in less severe cases.
- A trend towards increased inflammatory cell infiltration was observed in DCM patients with lower ejection fractions.
Conclusions:
- Monocyte chemoattractant protein 1 (MCP-1) levels are dynamically regulated and increase with the deterioration of left ventricular function in DCM.
- Elevated MCP-1 may contribute to myocyte damage through the infiltration and activation of monocytes in the cardiac tissue.
- MCP-1 serves as a potential biomarker for disease severity and a therapeutic target in dilated cardiomyopathy.
Abstract:
The cytotoxic action of leukocytes may be a most probable cause of cardiac myocyte damage seen in chronic myocarditis and dilated cardiomyopathy (DCM). The migration and tissue infiltration of leukocytes is regulated by chemotactic cytokines. Recently, the presence of monocyte chemoattractant protein 1 (MCP-1) messenger RNA has been demonstrated in endomyocardial biopsy tissue obtained from patients with DCM. This chemokine could contribute to enhanced leukocyte recruitment and activation resulting in chronic damage of cardiomyocytes. Accordingly, we sought to determine whether the severity of left ventricular dysfunction in DCM is associated with quantitative alterations of MCP-1 messenger RNA and MCP-1 protein in endomyocardial biopsy tissue. A group of DCM patients with low to moderate impairment of left ventricular function (ejection fraction 45.3+/-2.3%, n=7) was compared to patients with severe left ventricular dysfunction (ejection fraction 25.5+/-3.1%, n=7). MCP-1 messenger RNA expression was determined by quantitative polymerase chain reaction. MCP-1 protein and the presence of infiltrating inflammatory cells were detected by immunohistochemistry. DCM patients with severe left ventricular dysfunction showed a 2.35 fold higher MCP-1 messenger RNA expression when compared to DCM patients with less severe dysfunction (P=0.0229). Positive immunohistochemical staining for MCP-1 was found in all seven patients with severe left ventricular dysfunction and was particularly distinct within the cardiac interstitum. In five of seven patients with less severe systolic dysfunction, MCP-1 protein was found, but was less pronounced and distributed in patchy interstitial areas, close to intramyocardial vessels. Furthermore, there was a consistent trend toward a higher infiltration of inflammatory cells in DCM patients with lower ejection fraction. In conclusion, MCP-1 is dynamically regulated in DCM related deterioration of left ventricular function. This mechanism might contribute to myocyte damage via infiltrated and activated monocytes.