Published Online
on September 2, 2003

A more recent version of this article appeared on September 23, 2003

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Submitted on December 31, 2002
Revised on June 9, 2003
Accepted on July 6, 2003

Myocardial Collagen Turnover in Hypertrophic Cardiomyopathy

Raffaella Lombardi MD, Sandro Betocchi MD^*, Maria Angela Losi MD, Carlo Gabriele Tocchetti MD, Mariano Aversa MD, Marianna Miranda MD, Gianluigi D'Alessandro MD, Alessandra Cacace; , Quirino Ciampi MD, and Massimo Chiariello MD

From the Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University of Naples, Naples, Italy.

^* To whom correspondence should be addressed. E-mail: sandro.betocchi{at}unina.it.

Background--Myocardial interstitial fibrosis is a characteristic of hypertrophic cardiomyopathy (HCM). This study evaluates the collagen turnover in HCM and its impact on left ventricular (LV) diastolic function.

Methods and Results--Thirty-six HCM patients and 14 sex- and age-matched controls were studied. Collagen turnover was assessed as follows. By radioimmunoassay, a byproduct of collagen III synthesis (PIIINP) and 3 peptides resulting from collagen I synthesis (PICP and PINP) and degradation (ICTP) were measured. By ELISA, matrix metalloproteinases (MMPs) were determined, as follows: active MMP-2; active MMP-9; and MMP-1 as active, free (as active MMP-1 plus its precursor), and total (as free MMP-1 plus MMP-1/tissue inhibitor complexes). Tissue inhibitor of metalloproteinases-1 (TIMP-1) was also assayed. All patients underwent echocardiography. The difference in duration between transmitral forward (A) and pulmonary venous retrograde (AR) waves (A-Ar) was considered an estimate of passive diastolic function. Furthermore, restrictive or pseudonormal LV filling patterns were considered to identify patients with passive diastolic dysfunction. Patients had higher levels of PIIINP, ICTP, MMP-2, MMP-9, and total TIMP-1 than did controls. PIIINP was inversely related to LV end-diastolic diameter. A-Ar was inversely related to PICP, PINP, and their differences with ICTP (estimates of collagen I buildup). Furthermore, A-Ar was directly related to MMP-1 and MMP-2.

Conclusions--As compared with controls, collagen turnover is enhanced in HCM patients. As collagen I synthesis prevails over degradation and MMP-1 and MMP-2 are inhibited, passive diastolic dysfunction occurs in patients with HCM.

Key words: diastole • cardiomyopathy • collagen • peptides • metalloproteinases

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