Angiotensin II-mediated up-regulation of connective tissue growth factor promotes atrial tissue fibrosis in the canine atrial fibrillation model

Kiryu, Michiro; Niwano, Shinichi; Niwano, Hiroe; Kishihara, Jun; Aoyama, Yuya; Fukaya, Hidehira; Masaki, Yoshihiko; Izumi, Tohru

doi:10.1093/europace/eus052

Cited by 36 publications

(32 citation statements)

References 32 publications

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“…10 In the last two decades, Ang-(1-7), which is another heptapeptide formed from Ang-I and/or Ang-II, became a novel focus in the RAS because of its protective roles in the cardiovascular system (i.e. vasodilation and antifibrotic effects).…”

Section: Discussionmentioning

confidence: 99%

Effects of the angiotensin-(1-7)/Mas/PI3K/Akt/nitric oxide axis and the possible role of atrial natriuretic peptide in an acute atrial tachycardia canine model

Zhao

Liu

et al. 2014

J Renin Angiotensin Aldosterone Syst

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Objective: To investigate the effects of the angiotensin-(1-7) signaling pathway and the possible role of atrial natriuretic peptide (ANP) on atrial electrical remodeling in canines with acute atrial tachycardia. Methods: Forty dogs were randomly assigned to eight groups (five dogs/group): sham, paced control, paced + angiotensin-(1-7), paced + angiotensin-(1-7) + Mas inhibitor, paced + angiotensin-(1-7) + Akt inhibitor, paced + angiotensin-(1-7) + PI3K inhibitor, paced + angiotensin-(1-7) + nitric oxide (NO) inhibitor, and paced + angiotensin-(1-7) + A-71915 (ANP receptor antagonist). Rapid atrial pacing was maintained at 600 bpm for 2 h for all groups, except the sham group, and angiotensin-(1-7) (6 μg kg−1 h−1), Mas inhibitor (5.83 μg kg−1 h−1), Akt inhibitor (2.14 μg kg−1 h−1), PI3K inhibitor (2.86 μg kg−1 h−1), NO synthase inhibitor (180 μg kg−1h−1), or A-71915 (0.30 μg kg−1 h−1) were administered intravenously. Atrial effective refractory periods, inducibility, and duration of atrial fibrillation (pacing cycle lengths: 300, 250, and 200 ms), and left atrial ANP concentrations were measured. Results: After pacing, the atrial effective refractory periods at the six sites shortened with increased inducibility and duration of atrial fibrillation, which was attenuated by angiotensin-(1-7), and increased ANP concentrations, which was promoted by angiotensin-(1-7) (paced control vs. sham; P < 0.05). All inhibitors and A-71915 blocked the electrophysiological effects of angiotensin-(1-7). ANP secretion induced by angiotensin-(1-7) was also blocked by all inhibitors. Conclusion: Angiotensin-(1-7) prevented acute electrical remodeling in canines with acute atrial tachycardia via the angiotensin-(1-7)/Mas/PI3K/Akt/NO signaling pathway. ANP was related to the anti-arrhythmic effects of angiotensin-(1-7).

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Section: Discussionmentioning

confidence: 99%

Effects of the angiotensin-(1-7)/Mas/PI3K/Akt/nitric oxide axis and the possible role of atrial natriuretic peptide in an acute atrial tachycardia canine model

Zhao

Liu

et al. 2014

J Renin Angiotensin Aldosterone Syst

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“…30 Similar effects have been observed in a dog model with atrial tachypacing. 31 In addition, in a rat model of OSA, repetitive obstructive respiratory events during 4 weeks resulted in structural atrial remodeling characterized by increased fibrosis formation and cellular hypertrophy. 16,18 Effect of RDN on Atrial Arrhythmias, RAAS Activation, and Atrial Oxidative Stress Previously, we have shown that RDN ameliorated the hypoxia/NTP-induced shortening of atrial effective refractory period and inhibited artificially induced episodes of AF during 1 single obstructive respiratory event.…”

Section: Potential Impact Of Repetitive Obstructive Respiratory Eventmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of Renal Denervation on Neurohumoral Activation Triggering Atrial Fibrillation in Obstructive Sleep Apnea

Linz

Hohl²,

Nickel³

et al. 2013

Hypertension

117

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O bstructive sleep apnea (OSA) is associated with a high prevalence of cardiovascular diseases such as hypertension and atrial fibrillation (AF).1,2 OSA is characterized by repetitive total collapses of the upper airway, leading to intermittent hypoxia, forced inspiration-induced negative tracheal and thoracic pressure (NTP), postapneic blood pressure rises, 3 and increased sympathetic activation. 4 Stimulation of vascular and cardiac α-and β-adrenoceptors by the neurotransmitters of the sympathetic nervous system leads to neurohumoral activation and increased reactive oxygen species (ROS) generation via nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase) 5 and mitochondria. 6 Furthermore, elevated NADPHoxidase activity is associated with permanent AF in mice and humans 7,8 and, in particular, with an early event in the natural history of postoperative AF. 9 Therefore, increased sympathetic activation may play an important role for the initiation and progression of AF in OSA.Modulation of the autonomic nervous system by renal sympathetic denervation (RDN) has been shown to be effective in reducing both renal norepinephrine spillover and muscle sympathetic nerve activity. [10][11][12] In a pig model mimicking OSA, 1-time applied NTP during 2 minutes of obstructive respiratory events increased inducibility of AF by premature electric stimuli, 13,14 which could be reduced by β-adrenoceptor blockade and RDN. 15 However, the role of sympathetic activation for spontaneous AF episodes and the reasons for the progression to permanent AF in OSA Abstract-Obstructive sleep apnea is characterized by repetitive collapses of the upper airway, negative thoracic pressure periods, and intermittent hypoxia, stimulating the autonomic nervous system. The increased sympathetic drive during obstructive sleep apnea results in postapneic blood pressure rises and neurohumoral activation potentially involved in the initiation and progression to permanent atrial fibrillation (AF). In a pig model mimicking obstructive sleep apnea, we studied the effects of repetitive obstructive respiratory events for 4 hours on the occurrence of spontaneous AF episodes, postapneic blood pressure rises, and neurohumoral activation. In addition, renal sympathetic denervation was performed to investigate the impact of the sympathetic nervous system. Repetitive obstructive respiratory events caused pronounced postapneic blood pressure rises, prolonged duration of spontaneous AF episodes triggered by spontaneous atrial beats, and increased plasma renin activity and aldosterone concentrations. This was associated with increased nicotinamide adenine dinucleotide phosphate-oxidase activity, reduced antioxidative capacity, and elevated expression of connective tissue growth factor, a redox-sensitive mediator of fibrosis. Renal sympathetic denervation inhibited postapneic blood pressure rises and decreased plasma renin activity and aldosterone concentrations. The occurrence and duration of spontaneous AF were reduced comparable with a comb...

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“…AT1R antagonism appeared to attenuate collagen synthesis, fibrosis and structural remodeling in rabbit model of atrial fibrillation and it was proposed that OLM acted through the inhibition of p38MAPK/ERK pathway in cardiac fibroblasts [14]. Furthermore, in the canine model of atrial fibrillation, interstitial fibrosis was caused by the AT1R-dependent up-regulation of strong mediator of ECM synthesis, CTGF, and this effect was partially abolished by OLM [15].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, OLM administered after a myocardial infarction attenuated injury-evoked up-regulation of BAX protein, Fas receptor and Fas ligand [16]. Similarly, the induction of TNF-a expression in the rat model of steatohepatitis was limited by the inhibition of AT1R signaling by OLM [15]. In a study of experimental autoimmune myocarditis OLM prevented apoptosis by decreasing the levels of mediators of oxidative stress, endoplasmic reticulum stress, and cardiac inflammatory mediators [17].…”

Section: Discussionmentioning

confidence: 99%

A novel approach for preventing esophageal stricture formation: olmesartan prevented apoptosis

Dereli

Krazinski

Ayvaz

et al. 2014

Folia Histochem Cytobiol.

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Accidentally ingested corrosive substances can cause functional and structural damage to the esophageal tissue resulting in stricture formation. It has been reported that the administration of olmesartan (OLM) can have anti-inflammatory, antifibrotic and antiapoptotic effects on injured tissue. The aim of our study was to check if OLM could prevent formation of scars in the corrosive esophageal burn model. Fifty-one Wistar Albino rats were divided into six groups: Control, Sham, OLM, Sham + OLM, Burn, and Burn + OLM. Olmesartan (5 mg/kg) was given by gavage once per day for 21 consecutive days after injury. The morphology of the esophagus was assessed after Masson trichrome staining, and apoptosis was evaluated using the terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) method. The serum nucleosomes (as an indicator of apoptosis), serum p53 protein, and esophageal tissue p53 protein levels of each group were measured by immunoassays. Muscularis mucosa damage, submucosal collagen deposition, and tunica muscularis injury in the Burn + OLM group decreased significantly compared with the Burn group (p < 0.05). Similarly, the number of apoptotic cells in the Burn + OLM group decreased compared with the Burn group (p < 0.05). Serum levels of nucleosomes and p53 and tissue of p53 protein did not differ between the groups. Exogenously administered OLM can effectively prevent the occurrence of esophageal strictures caused by corrosive esophageal burns.

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Angiotensin II-mediated up-regulation of connective tissue growth factor promotes atrial tissue fibrosis in the canine atrial fibrillation model

Cited by 36 publications

References 32 publications

Effects of the angiotensin-(1-7)/Mas/PI3K/Akt/nitric oxide axis and the possible role of atrial natriuretic peptide in an acute atrial tachycardia canine model

Effects of the angiotensin-(1-7)/Mas/PI3K/Akt/nitric oxide axis and the possible role of atrial natriuretic peptide in an acute atrial tachycardia canine model

Effect of Renal Denervation on Neurohumoral Activation Triggering Atrial Fibrillation in Obstructive Sleep Apnea

A novel approach for preventing esophageal stricture formation: olmesartan prevented apoptosis

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