Korean Circ J.  2014 Jul;44(4):233-242. 10.4070/kcj.2014.44.4.233.

Histological and Biochemical Comparisons between Right Atrium and Left Atrium in Patients with Mitral Valvular Atrial Fibrillation

• Park JH
• Lee JS
• Ko YG
• Lee SH
• Lee BS
• Kang SM
• Chang BC
• Pak HN

• KMID: 2223884
• DOI: http://doi.org/10.4070/kcj.2014.44.4.233

Abstract

BACKGROUND AND OBJECTIVES
It has been known that the dominant driver of atrial fibrillation (AF) exists in the left atrium (LA) and the incidence of systemic thromboembolism is higher than that of pulmonary thromboembolism in patients with AF. Therefore, we hypothesized that histological and biochemical characteristics of the LA and the right atrium (RA) are different in patients with mitral valvular AF.
SUBJECTS AND METHODS
We analyzed the histology and messenger ribonucleic acid (mRNA) or protein expression associated with endothelial function and thrombogenesis in 33 human atrial appendage tissues (20 LA tissues, 13 RA tissues) taken from 25 patients {57.7+/-11.3 years old, 44% males, AF: sinus rhythm (SR)=17:8} with mitral valve disease. We also performed whole mRNA quantification in 8 tissues (both LA and RA tissues from 4 patients) by using next generation sequencing (NGS).
RESULTS
1) The degree of fibrosis (p=0.001) and subendocardial smooth muscle thickness (p=0.004) were significantly greater in the LA than in the RA. 2) More advanced matrix fibrosis was found in the LA of patients with AF than in the LA of patients with SR (p=0.046), but not in the RA. 3) There was no LA-RA difference in protein (Western blot) and mRNA {quantitative real-time polymerase chain reaction (qRT-PCR)} expressions of NF-kappaB, 3-NT, CD31, E-selectin, inducible NO synthase, stromal cell-derived factor-1alpha, Endothelin-1, platelet-derived growth factor, myeloperoxidase, or NCX, except for higher mRNA expression of HCN4 in the RA (qRT-PCR, p=0.026) and that of KCNN1 in the LA (NGS, p=0.016).
CONCLUSION
More advanced matrix and subendocardial remodeling were noticed in the LA than in the RA in patients with mitral valvular AF. However, the expressions of tissue factors associated with thrombogenesis were not significantly different between the RA and the LA.

Keyword

Atrial fibrillation; Mitral valve disease; Fibrosis; Subendocardium

MeSH Terms

Atrial Appendage
Atrial Fibrillation*
Chemokine CXCL12
E-Selectin
Endothelin-1
Fibrosis
Heart Atria*
Humans
Incidence
Male
Mitral Valve
Muscle, Smooth
NF-kappa B
Nitric Oxide Synthase
Peroxidase
Platelet-Derived Growth Factor
Pulmonary Embolism
Real-Time Polymerase Chain Reaction
RNA
RNA, Messenger
Thromboembolism
Thromboplastin
Chemokine CXCL12
E-Selectin
Endothelin-1
NF-kappa B
Nitric Oxide Synthase
Peroxidase
Platelet-Derived Growth Factor
RNA
RNA, Messenger
Thromboplastin

Figure

• 

  Fig. 1 Diagram of the mechanisms of multiple tissue factors associated with thrombosis. NO: nitric oxide, TNF: tumor necrosis factor, IL: interleukin, Ap-1/Sp-1: Ap-1/Sp-1 transcription factors, Egr-1: early growth response protein-1, SDF: stromal cell-derived factor, PECAM: platelet endothelial cell adhesion molecule, PDGF: platelet-derived growth factor, BMEPC: bone marrow-derived endothelial progenitor cells.

• 

  Fig. 2 Masson's trichrome (MT) staining (A) and α-smooth muscle actin (SMA) staining (B) of AF-LA, SR-LA, AF-RA, and SR-RA. AF: atrial fibrillation, LA: left atrium, RA: right atrium, SR: sinus rhythm.

• 

  Fig. 3 Scatter plots of fibrosis area (%) and thickness of the subendocardial smooth muscle layer (mm) for the LA and RA. Most of the remodeling occurred in the fibrillating LA followed by LA showing sinus rhythm. AF: atrial fibrillation, LA: left atrium, RA: right atrium, SR: sinus rhythm.

• 

  Fig. 4 Western blot analysis of pNF-κB, CD31, E-selectin, iNOS, SDF-1α, Endothelin-1, PDGF, and MPO showed that the protein expression levels were not significantly different between the LA and the RA. LA: left atrium, RA: right atrium, iNOS: inducible NO synthase, SDF-1: stromal cell-derived factor-1, PDGF: platelet-derived growth factor, MPO: myeloperoxidase.

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