Is Structural Remodeling of Fibrillated Atria the Consequence of Tissue Hypoxia?

Ogi, Hiroshi; Nakano, Yukiko; Niida, Shumpei; Dote, Keigo; Hirai, Yukoh; Suenari, Kazuyosi; Tonouchi, Yukiji; Oda, Noboru; Makita, Yuko; Ueda, Shigeyuki; Kajihara, Kenta; Imai, Kyoichi; Sueda, Takuya; Chayama, Kazuaki; Kihara, Yasuki

doi:10.1253/circj.cj-09-0969

Cited by 47 publications

(41 citation statements)

References 49 publications

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“…Smoking, airway inflammation, hypoxia, hypercapnia, pulmonary hypertension, β-adrenergic agonist and steroids all contribute to ultimately causing or worsening AF [11][12][13][14][15].…”

Section: Copd and Atrial Fibrillation: Potential Causes Of Arrhythmiamentioning

confidence: 99%

“…Matrix metalloproteinase 9 (MMP9) expression is increased in the atrium in a patient with AF and potentially causes atrial remodeling. It was shown via Immunofluorescence that there was excess production and colocalization of HIF-1α, VEGF and MMP-9 within the endothelium of the atrial arteries in the AF group as compared to patients without AF [13].…”

Section: Copd and Atrial Fibrillation: Potential Causes Of Arrhythmiamentioning

confidence: 99%

See 1 more Smart Citation

The Association between Chronic Obstructive Pulmonary Disease (COPD) and Atrial Fibrillation: A Review

Shah¹,

Desai²

2017

Chron Obstruct Pulmon Dis

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COPD is one of the leading causes of Mortality & Morbidity in the US and is associated with a wide variety of cardiovascular diseases especially arrhythmias, angina, myocardial infarction and congestive heart failure and is directly associated with the severity of COPD described in the GOLD initiative. COPD is an independent risk factor for AF/AFL. Smoking, hypoxia and inflammation all contribute to AF in COPD patients mainly via atrial remodeling while hypercapnia contributes to it via increasing refractoriness of the atrial musculature and a delay in the return of the refractoriness to normal after resolution of the hypercapnia. The most common EKG abnormality found in patients with COPD is P pulmonale and the PQ interval is the strongest predictor of developing AF. The P wave Dispersion (PwD) was also an independent risk factor for the development of AF and was found to be more in the acute phase than in the stable phase.The BODE index, an important prognostic score among patients hospitalized with a COPD exacerbation has a direct co relation with the prevalence of AF/AFL while the DECAF score, which was found to be superior to the CURB 65 score as a mortality predictor for hospitalized patients, includes AF as one of the criteria. Chronic hypoxemia is one of the main reasons for altered pulmonary vein anatomy and hence the presence of COPD was identified as an independent risk factor for the recurrence of atrial tachyarrhythmias after catheter ablation in patients with COPD and the absence of COPD was also found to be an independent predictor for a successful electrocardioversion. These patients were also found to have an increased incidence of non-PV foci for the arrhythmias. Oral glucocorticoids were associated with an increased risk of developing AF especially high dose steroids. It is recommended to correct the underlying respiratory decompensation while treating patients with AF as they render the treatment of AF ineffective. Nondihydropyridine calcium channel blockers should be used as first line rate control agents for AF in patients with concomitant COPD while the β-blockers, sotalol, propafenone can be used in patients with obstructive lung disease who do not have bronchospasm.

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“…Smoking, airway inflammation, hypoxia, hypercapnia, pulmonary hypertension, β-adrenergic agonist and steroids all contribute to ultimately causing or worsening AF [11][12][13][14][15].…”

Section: Copd and Atrial Fibrillation: Potential Causes Of Arrhythmiamentioning

confidence: 99%

Section: Copd and Atrial Fibrillation: Potential Causes Of Arrhythmiamentioning

confidence: 99%

The Association between Chronic Obstructive Pulmonary Disease (COPD) and Atrial Fibrillation: A Review

Shah¹,

Desai²

2017

Chron Obstruct Pulmon Dis

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“…Hypoxia-induced vascular endothelial growth factor (VEGF) expression is strongly regulated by hypoxia-inducible factor-1a (HIF-1a), the transcriptional factor for VEGF, which is a critical modulator for sensing and responding to changes in the oxygen concentration [57]. MMP-9 expression increases in fibrillating atrial tissue, and may contribute to atrial structural remodeling of AF [57]. It is possible that upregulation of HIF-1a/VEGF is involved in the enhancement of MMP-9 expression under hypoxic conditions [57].…”

Section: Arrhythmogenic Mechanisms In Copdmentioning

confidence: 99%

“…MMP-9 expression increases in fibrillating atrial tissue, and may contribute to atrial structural remodeling of AF [57]. It is possible that upregulation of HIF-1a/VEGF is involved in the enhancement of MMP-9 expression under hypoxic conditions [57]. Furthermore, Xu et al reported increased levels of Toll-like receptor 2 (TLR2), HIF-1a and MMP-9 in patients with persistent and permanent AF, and suggested that TLR2 and HIF-1a may promote left atrial structural remodeling [58].…”

Section: Arrhythmogenic Mechanisms In Copdmentioning

confidence: 99%

Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease

Goudis¹,

Konstantinidis

Ntalas

et al. 2015

International Journal of Cardiology

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“…In patients with AF, it has been reported that the atrial HIF-1α level rises with the increasing expression level of MMP-9 (24). MMP-9, as an important protease in the MMP family, is associated with myocardial matrix remodeling (25), and its increasing activity can result in acute myocardial fibrosis (26,27).…”

Section: Discussionmentioning

confidence: 99%

Significance of hypoxia-inducible factor-1α expression with atrial fibrosis in rats induced with isoproterenol

Zhang

Chen

et al. 2014

Experimental and Therapeutic Medicine

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Atrial interstitial fibrosis plays a dual role in inducing and maintaining atrial fibrillation (AF). Hypoxia-inducible factor-1α (HIF-1α) has been reported as closely associated with renal, liver and pulmonary fibrosis diseases. However, whether HIF-1α is involved in myocardial fibrosis, and the associations between HIF-1α, transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) remain unknown. Therefore, this area warrants studying for the significance of AF diagnosis and treatment. The present study investigated the expression of HIF-1α in atrial fibrosis and its possible mechanism in isoproterenol (ISO)-induced rats. The three groups of rats; control, ISO and ISO plus sirolimus [also known as rapamycin (Rapa)], were treated for 15 days and sacrificed to remove the myocardial tissues. The expression levels of HIF-1α, TGF-β1 and MMP-9 and their associations with atrial fibrosis were examined through histomorphology and protein and mRNA levels. The protein and mRNA levels of HIF-1α, TGF-β1 and MMP-9 in the ISO group were increased markedly (P<0.01) compared with the control group, while those in the Rapa group were clearly decreased (P<0.01) compared with the ISO group. The protein and mRNA levels of HIF-1α, TGF-β1 and MMP-9 were positively correlated (P<0.01) with atrial fibrosis (collagen volume fraction index), as were the HIF-1α, TGF-β1 and MMP-9 mRNA levels (P<0.01) and the mRNA levels between MMP-9 and TGF-β1 (P<0.01). During the process of atrial fibrosis in ISO-induced rats, HIF-1α promotes the expression of TGF-β1 and MMP-9 protein, and thus is involved in in atrial fibrosis.

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Is Structural Remodeling of Fibrillated Atria the Consequence of Tissue Hypoxia?

Cited by 47 publications

References 49 publications

The Association between Chronic Obstructive Pulmonary Disease (COPD) and Atrial Fibrillation: A Review

The Association between Chronic Obstructive Pulmonary Disease (COPD) and Atrial Fibrillation: A Review

Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease

Significance of hypoxia-inducible factor-1α expression with atrial fibrosis in rats induced with isoproterenol

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