Procollagen propeptides: serum markers for atrial fibrosis?

Neuberger, Hans‐Ruprecht; Cacciatore, Angela; Reil, Jan‐Christian; Gräber, Stefan; Schäfers, Hans‐Joachim; Ukena, Christian; Böhm, Michael; Mewis, Christian

doi:10.1007/s00392-012-0440-6

Cited by 20 publications

(7 citation statements)

References 15 publications

(19 reference statements)

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“…In liver fibrosis [19, 24, 29], idiopathic pulmonary arterial hypertension, cystic fibrosis [25], renal failure [38] and cardiac fibrosis [16, 30], serum concentrations of PICP, PIIINP, HA, and LN are believed to reflect the level of fibrosis. In experimental models of subarachnoid hemorrhage, increased concentrations of PICP and PIIINP in the CSF, as well as leptomeningeal deposition of collagen Types I and III, have been found [23, 30, 32, 41]. The fibril-forming collagens (types I-III) are synthesized by mesenchymal cells as procollagens.…”

Section: Discussionmentioning

confidence: 99%

High fibrosis indices in cerebrospinal fluid of patients with shunt-dependent post-traumatic chronic hydrocephalus

Wang

et al. 2016

Translational Neuroscience

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ObjectiveA possible relationship between fibrosis along the route of cerebrospinal fluid (CSF) flow and the subsequent development of hydrocephalus has been indicated in previous studies. These changes in the fibrosis index may reflect the severity of hydrocephalus and could potentially become a diagnostic tool. The object of this study was to analyze the levels of procollagen type I C-terminal propeptide (PICP), procollagen type III N-terminal propeptide (PIIINP), hyaluronic acid (HA), and laminin (LN) in the CSF of patients with post-traumatic hydrocephalus and determine the significance of their presence.Subjects and methodsForty-four patients were included in the study: 24 patients with shunt-dependent post-traumatic hydrocephalus (group A - hydrocephalus group); ten brain trauma patients without any sign of hydrocephalus (group B - trauma group); ten patients without brain trauma and hydrocephalus (group C - normal control group). CSF levels of PICP, PIIINP, HA, LN and transforming growth factor-β1(TGF-β1) were detected using enzyme-linked immunosorbent assay (ELISA).ResultsLevels of PICP, PIIINP, HA, and LN in the group of hydrocephalus patients were significantly higher than those in the post-trauma patients without hydrocephalus (p < 0.05) and normal control patients (p < 0.05). Moreover, the increased levels of PICP, PIIINP, HA, and LN were positively correlated with the level of TGF-β1 (p < 0.05).ConclusionWe demonstrated an increase of fibrosis factors including PICP, PIIINP, HA, and LN, that was positively correlated with TGF-β1 levels. This indicates an important role for the process of fibrosis in the development of post-traumatic chronic hydrocephalus and shows the potential utility of PICP, PIIINP, HA, and LN as a diagnostic index in shunt-dependent post-traumatic chronic hydrocephalus.

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Section: Discussionmentioning

confidence: 99%

High fibrosis indices in cerebrospinal fluid of patients with shunt-dependent post-traumatic chronic hydrocephalus

Wang

et al. 2016

Translational Neuroscience

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“…Furthermore, a negative correlation between the serum PINP concentration and the degree of fibrosis in the atria was observed. 80 The reason behind these discrepant findings is not clear, but could potentially be related to variable pathologies, age groups, small number of patients enrolled (Table 1), chronicity of AF and degree of fibrosis. It is therefore essential that these biomarkers are validated in large prospective multicenter studies to assess their incremental value in predicting AF or PoAF before they can be accepted as markers of high risk for AF.…”

Section: Mechanism Underlying Atrial Fibrillation and Circulatory Biomentioning

confidence: 99%

“…78 Various peptides and proteins released during collagen synthesis, maturation, and remodeling have been used to characterize the substrate and risk for AF. 62,79,80 Collagen I and III are secreted as procollagen precursors containing amino- (CINP, CIIINP) and carboxyl-terminal (PICP, PIIICP) propeptides 58,81 that are released into the circulation by proteases, and their levels correlate with the rate of collagen synthesis (Figure 3). Collagen degradation results in the release of a carboxyl-terminal telopeptide of collagen I (CITP) and collagen III (CIIITP).…”

Section: Mechanism Underlying Atrial Fibrillation and Circulatory Biomentioning

confidence: 99%

“…58,81,83 A summary of markers of ECM turnover associated with AF and/or PoAF in humans is provided in Tables 1 and 2. 62,72,74,78–80,84–100 Kallergis et al 79 reported that serum markers of collagen type 1 turnover PICP and CITP were significantly higher in persistent AF patients compared to healthy control subjects, and the levels of PICP, but not CITP, were higher in persistent AF patients than paroxysmal. Persistent AF patients also had a lower level of MMP-1 and increased levels of TIMP-1, suggesting that overall collagen type 1 synthesis was increased and the observed increase in collagen-1 degradation was insufficient to compensate for increased synthesis resulting in progression of fibrosis in patients with persistent AF.…”

Section: Mechanism Underlying Atrial Fibrillation and Circulatory Biomentioning

confidence: 99%

“…The enthusiasm for these biomarkers as predictive of atrial fibrosis as a substrate for PoAF is also decreased by other studies that did not confirm these findings. 80 Neuberger et al 80 prospectively studied 28 patients in SR undergoing cardiac surgery, and PICP, PIIINP and CITP levels were not correlated to left or right atrial collagen content or to the spatial heterogeneity of atrial fibrosis despite the observation that spatial heterogeneity of fibrosis had a direct correlation to interstitial collagen content. Furthermore, a negative correlation between the serum PINP concentration and the degree of fibrosis in the atria was observed.…”

Section: Mechanism Underlying Atrial Fibrillation and Circulatory Biomentioning

confidence: 99%

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Circulating Biomarkers Predictive of Postoperative Atrial Fibrillation

Turagam

Mirza

Werner

et al. 2016

Cardiology in Review

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Postoperative atrial fibrillation (PoAF), a common complication of cardiac surgery, contributes significantly to morbidity, mortality, and increasing health care costs. Despite advances in surgical and medical management, the overall incidence of PoAF has not changed significantly, partly due to the limited understanding of mechanisms underlying acute surgery-related factors, such as myocardial injury, inflammation, sympathetic activation, and oxidative stress, which play an important role in the initiation of PoAF, while a preexisting atrial substrate appears to be more important in the maintenance of this dysrhythmia. Thus, in a majority of patients, PoAF becomes a manifestation of an underlying arrhythmogenic substrate that is unmasked following acute surgical stress. As such, the ability to identify which patients have this proarrhythmic substrate and are, therefore, at high risk for developing AF postoperatively, is important for the improved selection for prophylactic interventions, closer monitoring for complications, and establishing the probability of AF in the long term. This review highlights the role of the underlying substrate in promoting PoAF, proposed mechanisms, and the potential role of serum biomarkers to identify patients at risk for PoAF.

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