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Acta Physiol (Oxf). 2017 Aug;220(4):432-445. doi: 10.1111/apha.12835. Epub 2017 Jan 16.

A comparison of left and right atrial fibroblasts reveals different collagen production activity and stress-induced mitogen-activated protein kinase signalling in rats.

Chung CC1,2, Kao YH1,3, Yao CJ4,5, Lin YK2, Chen YJ1,2.

Author information

1
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
2
Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
3
Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
4
Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
5
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Abstract

AIM:

Atrial fibrosis plays a pivotal role in the pathophysiology of heart failure (HF). The left atrium (LA) experiences greater fibrosis than the right atrium (RA) during HF. It is not clear whether LA cardiac fibroblasts contain distinctive activities that predispose LA to fibrosis.

METHODS:

LA and RA fibrosis were evaluated in healthy and isoproterenol-induced HF Sprague Dawley rats. Rat LA and RA primary isolated fibroblasts were subjected to proliferation assay, oxidative stress assay, cell migration analysis, collagen measurement, cytokine array and Western blot.

RESULTS:

Healthy rat LA and RA had a similar extent of collagen deposition. HF significantly increased fibrosis to a greater severity in LA than in RA. Compared to isolated RA fibroblasts, the in vitro experiments showed that isolated LA fibroblasts had higher oxidative stress and exhibited higher collagen, transforming growth factor-β1, connective tissue growth factor production and less vascular endothelial growth factor (VEGF) production, but had similar migration, myofibroblast differentiation and proliferation activities. VEGF significantly increased the collagen production ability of LA fibroblasts, but not RA fibroblasts. LA fibroblasts had more phosphorylated ERK1/2 and P38 expression. ERK inhibitor (PD98059, 50 μmol L-1 ) significantly attenuated collagen production and increased VEGF production in RA fibroblasts but not in LA fibroblasts. P38 inhibitor (SB203580, 30 μmol L-1 ) significantly attenuated collagen production in LA fibroblasts but not in RA fibroblasts. P38 inhibitor also significantly increased VEGF production in RA and LA fibroblasts.

CONCLUSIONS:

Differences in profibrotic activity between LA and RA fibroblasts may be caused by different responses to mitogen-activated protein kinase signalling.

KEYWORDS:

fibroblasts; fibrosis; heart failure; left atrium; right atrium

PMID:
27875022
DOI:
10.1111/apha.12835
[Indexed for MEDLINE]

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