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.
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.
Authors: Anna Raskin; Stephan Lange; Katherine Banares; Robert C Lyon; Anke Zieseniss; Leonard K Lee; Katrina G Yamazaki; Henk L Granzier; Carol C Gregorio; Andrew D McCulloch; Jeffrey H Omens; Farah Sheikh Journal: J Biol Chem Date: 2012-07-09 Impact factor: 5.157
Authors: P Sipola; K Peuhkurinen; K Lauerma; M Husso; P Jääskeläinen; M Laakso; H J Aronen; J Risteli; J Kuusisto Journal: Heart Date: 2006-09 Impact factor: 5.994
Authors: Elif Elmas; Christina Doesch; Stephan Fluechter; Miriam Freundt; Christel Weiss; Siegfried Lang; Thorsten Kälsch; Dariush Haghi; Jana Papassotiriou; Jan Kunde; Stefan O Schoenberg; Martin Borggrefe; Theano Papavassiliu Journal: Int J Cardiovasc Imaging Date: 2010-09-26 Impact factor: 2.357
Authors: Justin P Zachariah; Steven D Colan; Peter Lang; John K Triedman; Mark E Alexander; Edward P Walsh; Charles I Berul; Frank Cecchin Journal: Circ Heart Fail Date: 2012-05-24 Impact factor: 8.790