Zusammenfassung
Ziel dieser Studie war es, die Hypothese eines veränderten Kollagenstoffwechsels bei Patienten mit hypertropher Kardiomyopathie (HCM) zu testen. Hierzu wurden zirkulierende Marker des Typ-I-Kollagenstoffwechsels untersucht und mit echokardiographischen Parametern der diastolischen Funktion korreliert.
Hintergrund
Die HCM ist eine häufige Erkrankung bei Erwachsenen mit unterschiedlicher klinischer Manifestation. Die linksventrikuläre Hypertrophie und der erhöhte intramyokardiale Kollagengehalt verursachen eine diastolische Dysfunktion.
Methoden
Bei 26 Patienten mit HCM und 38 Kontrollen (Alter: 57±3 und 54±2 Jahre, p=n.s.) wurden die Serumkonzentrationen der kollagenolytischen Matrixmetalloproteinase-1 (MMP-1) unnd deren Inhibitor TIMP-1, sowie die Marker für Typ-I-Kollagensynthese (PICP) und -degradation (ICTP) mittels ELISA und RIA bestimmt. Die diastolische Funktion wurde mittels Dopplerechokardiographie bestimmt.
Ergebnisse
Freies TIMP-1 war bei HCM im Vergleich zu den Kontrollen erhöht (216,78±9.89 vs. 183,77±7,57 ng/ml; p=0,006), ebenso PICP (165,92±10.26 vs. 114,57±6,38 μg/l; p<0,001). Freies MMP-1 war bei HCM signifikant erniedrigt (1,13±0,20 vs. 2,33±0,34; p=0,01). ICTP unterschied sich nicht. Die MMP-1/TIMP-1-Ratio war bei HCM significant erniedrigt (0,006±0,001 vs. 0,012±0,001, p=0,003). PICP korrelierte positiv mit der diastolischen E/A-Ratio (r =0,389; p=0,05) und der Septumdicke (r=0,484; p=0,01).
Schlussfolgerung
Der Serummarker der Kollagensynthese (PICP) ist bei Patienten mit HCM erhöht. Bei erhöhtem Serummarker für eine Hemmung der Kollagenolyse (TIMP-1) und einer Verschiebung der MMP-1/TIMP-1-Ratio zu Gunsten des Inhibitors ist eine Vermehrung des Kollagengehaltes (Fibrose) anzunehmen, die zur passiven diastolischen Dysfunktion bei Patienten mit HCM führt.
Summary
Objectives
The hypothesis of impaired collagenolysis in patients with hypertrophic cardiomyopathy (HCM) was tested by measuring serum markers of type-I collagen metabolism. These markers were correlated with echocardiographic parameters of diastolic function.
Background
HCM is a common disease in the adult population with a wide range of clinical manifestations. Left ventricular hypertrophy and increased intramyocardial collagen content are known to cause diastolic dysfunction in patients with HCM.
Methods
In 26 patients with HCM and 38 control subjects (aged: 57±3 and 54±2 years, p=n.s.) serum levels of collagenolytic matrixmetalloproteinase-1 (MMP-1) and its inhibitor TIMP-1, the markers for collagen type-I synthesis (PICP) and degradation (ICTP) were determined by ELISA and RIA. Diastolic function were determined by Doppler echocardiography.
Results
Free TIMP-1 was elevated in HCM compared to controls (216,78±9,89 vs 183.77±7.57 ng/ml ; p=0.006) as well as PICP (165.92±10.26 vs 114.57±6.38 μg/l; p<0.001). Free MMP-1 was significantly lower in HCM (1.13±0.20 vs 2.33±0.34; p=0.01). ICTP did not differ. The MMP-1/TIMP-1 ratio was significantly lower in HCM (0.006±0.001 vs 0.012±0.001, p=0.003). PICP correlated positively with diastolic E/A ratio (r=0.389; p=0.05) and septal thickness (r=0.484; p=0.01).
Conclusions
Serum marker of collagen synthesis (PICP) is increased in patients with HCM. Increased marker for inhibition of collagenolysis (TIMP-1) and a disturbed balance of collagen synthesis and degradation (ratio) with a predominance of inhibition of collagenolysis indicates collagen accumulation (fibrosis), which explains passive diastolic dysfunction in patients with HCM.
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Fassbach, M., Schwartzkopff, B. Elevated serum markers for collagen synthesis in patients with hypertrophic cardiomyopathy and diastolic dysfunction. ZS Kardiologie 94, 328–335 (2005). https://doi.org/10.1007/s00392-005-0214-5
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DOI: https://doi.org/10.1007/s00392-005-0214-5