Extracellular matrix alterations in patients with paroxysmal and persistent atrial fibrillation: biochemical assessment of collagen type-I turnover.

Department of Cardiology, University Hospital of Heraklion, Crete, Greece.
Journal of the American College of Cardiology (Impact Factor: 15.34). 07/2008; 52(3):211-5. DOI: 10.1016/j.jacc.2008.03.045
Source: PubMed

ABSTRACT We investigated whether the serum markers of collagen turnover differed in various forms of atrial fibrillation (AF) and in sinus rhythm (SR) in humans.
Structural alterations and fibrosis have been implicated in the generation and perpetuation of AF.
Serum C-terminal propeptide of collagen type-I (CICP), C-terminal telopeptide of collagen type-I (CITP), matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinases-1 were measured as markers of collagen synthesis and degradation in 70 patients with AF and 20 healthy control subjects in SR.
C-terminal propeptide of collagen type-I and CITP were significantly higher in AF patients than in control subjects (91 +/- 27 ng/ml vs. 67 +/- 11 ng/ml, p < 0.001 and 0.38 +/- 0.20 ng/ml vs. 0.25 +/- 0.08 ng/ml, p < 0.001, respectively). Persistent AF patients had higher levels of CICP (105 +/- 28 ng/ml vs. 80 +/- 21 ng/ml, p < 0.001), but not CITP, compared with those with paroxysmal AF. Patients with persistent AF had lower levels of matrix metalloproteinase-1 but increased levels of tissue inhibitor of matrix metalloproteinases-1 compared with patients with paroxysmal AF (11.90 +/- 4.79 ng/ml vs. 14.98 +/- 6.28 ng/ml, p = 0.03 and 155 +/- 45 ng/ml vs. 130 +/- 38 ng/ml, p < 0.001, respectively). Tissue inhibitor of matrix metalloproteinases-1 levels were significantly lower in control subjects compared with those in both paroxysmal and persistent AF patients (102 +/- 15 ng/ml vs. 130 +/- 38 ng/ml vs. 155 +/- 45 ng/ml, respectively, p < 0.001).
Serum markers of collagen type-I turnover differed significantly between patients with AF and SR. Furthermore, these markers also differed significantly between paroxysmal and persistent AF patients, suggesting that the intensity of the extracellular synthesis and degradation of collagen type-I may be related to the burden or type of AF.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims Collagen turnover and atrial fibrosis have been implicated in the generation and perpetuation of atrial fibrillation (AF). We evaluated the importance of serum markers of collagen turnover in predicting the outcome of electrical cardioversion (CV) of persistent AF and the relationship between AF and fibrosis. Methods and results Serum C-terminal pro-peptide of collagen type-I (CICP) and C-terminal telopeptide of collagen type-I (CITP) were measured in 164 patients with AF before and 2 months after CV. All the patients were successfully cardioverted to sinus rhythm (SR) although in 38 of them AF recurred. Baseline CICP levels were comparable in patients in SR 60 days after CV and in those who experienced a relapse of AF (85.08 +/- 16.99 vs. 87.55 +/- 10.43 ng/mL, respectively, P = ns). Baseline CITP levels were significantly higher in patients with AF recurrence compared with those who remained in SR (0.48 +/- 0.16 vs. 0.32 +/- 0.17 ng/mL, respectively, P < 0.0001). In the 126 patients who maintained the SR, CICP levels were significantly lower at the end of the study as compared with the baseline (63.74 +/- 15.92 vs. 85.08 +/- 16.99 ng/mL P = 0.003), while there was a mild increase in plasma CITP levels (0.36 +/- 0.21 vs. 0.32 +/- 0.17 ng/mL, respectively, P = 0.03). Conclusion Atrial fibrillation can result in alterations in atrial structure and architecture that make the atrial myocardium more susceptible to the maintenance of the arrhythmia. Sinus rhythm restoration could affect the fibrotic process occurring or exacerbating during AF course.
    Europace 08/2014; 16(12). DOI:10.1093/europace/eut401 · 3.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The cysteine protease cathepsin K (CatK) has been implicated in the pathogenesis of cardiovascular disease. We sought to determine the link between atrial fibrillation (AF) and plasma CatK levels and to investigate the expression of and therapeutic target for CatK in vivo and in vitro. Plasma CatK and extracellular matrix protein peptides (intact procollagen type I of N-terminal propeptide; carboxyl-terminal telopeptide of type I collagen [ICTP]) were measured in 209 consecutive patients with AF (paroxysmal AF, 146; persistent AF, 63) and 112 control subjects. In addition, the regulation of CatK expression was investigated in vivo and vitro. Patients with AF had higher plasma CatK and ICTP levels than did control subjects. Patients with persistent AF had higher levels of plasma CatK and ICTP than did patients with paroxysmal AF. CatK was correlated with ICTP concentration and left atrial diameter in all subjects. In rabbits, superoxide production, CatK activity, fibrosis, and the levels of atrial tissue angiotensin II, angiotensin type 1 receptor, gp91phox, phospho-p38 mitogen-activated protein kinase, and CatK were greater in those with tachypacing-induced AF than in controls, and these changes were reversed with angiotensin type 1 receptor antagonist. Olmesartan and mitogen-activated protein kinase inhibitor decreased the CatK expression induced by angiotensin II in rat neonatal myocytes. These data indicated that increased plasma CatK levels are linked with the presence of AF. Angiotensin type 1 receptor antagonist appears to be effective in alleviating atrial fibrosis in a rabbit AF model, partly reducing angiotensin type 1 receptor-p38mitogen-activated protein kinase-dependent and -independent CatK activation, thus preventing AF.
    Journal of the American Heart Association 10/2013; 2(6):e000503. DOI:10.1161/JAHA.113.000503
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Objectives: Alterations of collagen metabolism present in heart failure promote the fibrotic substrate for the development of atrial fibrillation. Myocardial collagen I synthesis and degradation can be assessed indirectly by the circulating biomarkers carboxy-terminal propeptide (PICP) and carboxy-terminal telopeptide (CITP), respectively. Design: We examined myocardial collagen type I metabolism in 143 patients with systolic heart failure (NYHA 2-4) in relation to coexisting atrial fibrillation. Results: Mean age was 75 years, blood pressure 134/80 mm Hg, ejection fraction 34%, serum PICP 81 µg/L and CITP 8.3 µg/L, and median plasma brain natriuretic peptide 215 pg/L; 77 were in atrial fibrillation. PICP and CITP related to left atrial diameter (r=0.22, P=0.013, and r=0.26, P=0.003) and CITP to pulmonary capillary wedge pressure and C-reactive protein (r=0.19, P=0.044, and r=0.29, P=0.003). A logistic regression suggested PICP (odds ratio per 1 µg/L change 1.01, P=0.012) and left ventricular end-diastolic volume (odds ratio per 1 mL change 0.98, P<0.001) independently associated with coexisting atrial fibrillation. Conclusion: Collagen type I metabolism is associated to left atrial size. Heart failure patients with coexisting atrial fibrillation exhibit more altered collagen type I metabolism than patients in sinus rhythm. This might represent more severe atrial and ventricular fibrosis.
    Scandinavian cardiovascular journal: SCJ 06/2014; DOI:10.3109/14017431.2014.940063 · 1.07 Impact Factor

Full-text (2 Sources)

Available from
Jun 2, 2014