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C-reactive protein co-expresses with tumor necrosis factor-alpha in the myocardium in human dilated cardiomyopathy
Mamoru Satoh1, Motoyuki Nakamura, Tomonari Akatsu
1Second Department of Internal Medicine, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan. m_satoh@imu.ncvc.go.jp
Insights
C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha) are elevated in dilated cardiomyopathy (DCM) patients, correlating with disease severity. Treatment with spironolactone and ACEIs/ARBs reduced these inflammatory markers.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- C-reactive protein (CRP) is found in cardiac tissue, stimulating proinflammatory cytokines.
- Cardiac tumor necrosis factor-alpha (TNF-alpha) is crucial in dilated cardiomyopathy (DCM) pathogenesis.
Purpose of the Study:
- Investigate CRP and TNF-alpha co-expression in DCM myocardium.
- Examine the association between CRP/TNF-alpha and clinical features in DCM patients.
Main Methods:
- Real-time RT-PCR to measure CRP and TNF-alpha mRNA in endomyocardial biopsies from 41 DCM patients and 16 controls.
- Immunohistochemistry and in situ hybridization to identify cellular sources of CRP and TNF-alpha.
- Correlation analysis of mRNA levels with clinical parameters and treatment regimens.
Main Results:
- Both CRP and TNF-alpha mRNA were expressed in DCM myocardium, but not in controls.
- CRP and TNF-alpha levels positively correlated and were localized in cardiomyocytes.
- Elevated mRNA levels correlated with reduced systolic function and increased left ventricular volume.
- mRNA levels were lower in patients treated with spironolactone plus ACEIs or ARBs.
Conclusions:
- Cardiac CRP and TNF-alpha may act as proinflammatory mediators in DCM, linked to clinical severity.
- Expression of CRP and TNF-alpha decreased with spironolactone and ACEI/ARB treatment in DCM patients.
Background:
C-reactive protein (CRP) has recently been reported to be present in cardiac tissue and to stimulate the production of proinflammatory cytokines. Cardiac expression of tumor necrosis factor-alpha (TNF-alpha) plays an important role in the pathogenesis of dilated cardiomyopathy (DCM).
Aims:
To determine whether CRP co-expresses with TNF-alpha in the myocardium and to examine its association with clinical features in patients with DCM.
Methods And Results:
Endomyocardial biopsy tissues were obtained from 41 DCM patients and 16 controls by right ventricular endomyocardial biopsy. Levels of CRP and TNF-alpha mRNA were measured by real-time RT-PCR. Immunohistochemistry and in situ hybridization were performed to identify the cellular sources of CRP and TNF-alpha. Both CRP and TNF-alpha mRNA were expressed in myocardium obtained from DCM patients, but not in controls. A positive correlation was found between CRP and TNF-alpha levels. CRP/TNF-alpha double staining was found to be colocalized in the cardiomyocytes of DCM patients. Both forms of mRNA were also expressed in cardiomyocytes. Both CRP and TNF-alpha mRNA levels were negatively correlated with systolic function and positively correlated with left ventricular volume in DCM patients. These mRNA levels were lower in DCM patients treated with a combination of spironolactone and either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) than in patients not treated with these drugs.
Conclusion:
Cardiac expression of CRP with TNF-alpha may function as a proinflammatory mediator in DCM and may be related to the clinical severity of DCM. Expression of both of these proteins was decreased in DCM patients receiving spironolactone and either ACEIs or ARBs.
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