Myocardial collagen turnover in hypertrophic cardiomyopathy.
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.


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.
Lombardi
Raffaella
R
Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University School of Medicine, Naples, Italy.
Betocchi
Sandro
S
Losi
Maria Angela
MA
Tocchetti
Carlo Gabriele
CG
Aversa
Mariano
M
Miranda
Marianna
M
D'Alessandro
Gianluigi
G
Cacace
Alessandra
A
Ciampi
Quirino
Q
Chiariello
Massimo
M
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I; D004452:Echocardiography; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D011347:Procollagen / Q000097:blood; D012016:Reference Values; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016277:Ventricular Function, Left
D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1