Elevated serum markers for collagen synthesis in patients with hypertrophic cardiomyopathy and diastolic dysfunction

Abstract

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. 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. 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. 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 mug/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). 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.