The fibrosis biomarkers procollagen

type III, N-terminal propeptide andtransforming growth factor β1 as foes forpatients with atrial fibrillation

To the Editor:

Cardiac fibrosis is thought to play a central role in thepathogenesis of atrial fibrillation (AF). Cardiac fibrosis ischaracterized by net accumulation of extracellular matrixproteins in the cardiac interstitium. Inflammatory cytokines,chemokines, and growth factors (such as transforminggrowth factor β1 (TGF-β1)) are some of the best-studiedmediators implicated in cardiac fibrosis. However, thepotential role of fibrosis biomarkers procollagen type III,N-terminal propeptide (PIIINP) and TGF-β1 in AF are stillunclear. Rosenberg et al 1 found that PIIINP levels wereassociated with risk of incident AF in a complex manner,with an association that appeared to be positive up tomedian levels but with little relationship beyond that.Moreover, TGF-β1 levels were not associated with AF risk.This study suggested that PIIINPmay serve as a foe and goodtherapeutic target for AF.

Numerous studies have found that TGF-β1 and PIIINPplay a key role in AF. Richter et al 2 demonstrated thatall markers showed a significant ablation-induced up-regulation (matrix metalloproteinase 9 (MMP-9): 1.8 ±0.1-fold, TGF-β1: 2.4 ± 0.4-fold, and PIIINP: 1.3 ± 0.1-fold).The area under the curve of MMP-9 and TGF-β1 correlatedwith the ablation-induced reduction of left atrial (LA)volume. The area under the curve of PIIINP independentlypredicted recurrent AF. Furthermore, Sonmez et al 3

indicated that PIIINP levels were significantly higher in AFpatients. PIIINP had a strong positive correlation with leftatrial volume (LAV) index. What is more, Kawamura et al 4

show that elevated baseline PIIINP concentration is anindependent predictor for AF recurrence after cardiover-sion. However, Mira et al 5 indicated that the TGF-β1messenger RNA and protein expression levels in patientswith AF were significantly higher than that in the control

group. These results show that PIIINP and TGF-β1 as foesfor patients with AF.

These findings demonstrated that PIIINP and TGF-β1may serve as good potential therapeutic target for AFPIIINP and TGF-β1 as foes for patients with AF. All in all,we greatly enjoyed reading the article by Rosenberg et al 1

and believe PIIINP and TGF-β1may be useful for preventionand treatment of patients with AF.

Am Heart J 2014;168:e15.0002-8703http://dx.doi.org/10.1016/j.ahj.2014.07.004

Hui Tao, MD

Wei Cao, MD

Kai-Hu Shi, PhD*

Department of Cardiothoracic Surgery

The Second Hospital of Anhui Medical University

Hefei, China

Cardiovascular Research Center

Anhui Medical University

Hefei, China

E-mail: ayskh3@hotmail.com

References1. Rosenberg MA, Maziarz M, Tan AY, et al. Circulating fibrosis

biomarkers and risk of atrial fibrillation: the CardiovascularHealth Study (CHS). Am Heart J 2014;167(5):723-728.e2.

2. Richter B, Gwechenberger M, Socas A, et al. Time course of markers oftissue repair after ablation of atrial fibrillation and their relation to leftatrial structural changes and clinical ablation outcome. Int J Cardiol2011;152(2):231-6.

3. Sonmez O, Ertem FU, Vatankulu MA, et al. Novel fibro-inflammationmarkers in assessing left atrial remodeling in non-valvular atrialfibrillation. Med Sci Monit 2014;20:463-70.

4. Kawamura M, Munetsugu Y, Kawasaki S, et al. Type IIIprocollagen-N-peptide as a predictor of persistentatrial fibrillation recurrence after cardioversion.Europace 2012;14(12):1719-25.

5. Mira YE, Muhuyati, Lu WH, et al. TGF-beta1 signal pathway in theregulation of inflammation in patients with atrial fibrillation. Asian Pac JTrop Med 2013;6(12):999-1003.