Cardiomyocyte-Derived Mitochondrial Superoxide Causes Myocardial Electrical Remodeling by Downregulating Potassium Channels and Related Molecules

Kurokawa, Syuhei; Niwano, Shinichi; Niwano, Hiroe; Murakami, Masami; Ishikawa, Shoko; Masaki, Yoshihiko; Tamaki, Hideaki; Toda, Toshifusa; Noda, Yoichi; Shimizu, Takahiko; Izumi, Tohru; Ako, Junya

doi:10.1253/circj.cj-13-1587

Cited by 15 publications

(14 citation statements)

References 33 publications

(19 reference statements)

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“…As regards the former, AGEs determine the impairing of Kv channel activity in vascular smooth muscle cells through glycation reaction. As regards the latter, the interaction between AGEs and their receptors represents a stimulus for oxidative stress, which is associated with a downregulation of Kv 1.2 and Kv 1.5 proteins and mRNA of expression [ 74 , 75 , 76 ]. These mechanisms cause the alteration of coronary blood flow regulation through the impairing of both non-endothelial- and endothelial-dependent vasodilatation mechanisms [ 73 ].…”

Section: Role Of Ion Channels In the Pathophysiological Continuum mentioning

confidence: 99%

Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels

Severino

D’Amato

Netti

et al. 2018

IJMS

101

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Diabetes mellitus is one the strongest risk factors for cardiovascular disease and, in particular, for ischemic heart disease (IHD). The pathophysiology of myocardial ischemia in diabetic patients is complex and not fully understood: some diabetic patients have mainly coronary stenosis obstructing blood flow to the myocardium; others present with coronary microvascular disease with an absence of plaques in the epicardial vessels. Ion channels acting in the cross-talk between the myocardial energy state and coronary blood flow may play a role in the pathophysiology of IHD in diabetic patients. In particular, some genetic variants for ATP-dependent potassium channels seem to be involved in the determinism of IHD.

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Section: Role Of Ion Channels In the Pathophysiological Continuum mentioning

confidence: 99%

Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels

Severino

D’Amato

Netti

et al. 2018

IJMS

101

View full text Add to dashboard Cite

show abstract

“…21 This is probably because AF is a complex disease with a multifactorial etiology. [31][32][33][34] In order to avoid a biased sampling from AF patients, we carefully selected patients in this study that strictly represent samples to elucidate AF-specific changes in the miRNAs of the human atrium. Importantly, electrical remodeling in atrial cardiomyocytes with chronic AF is distinct from those with paroxysmal AF.…”

Section: Regulation Of Mir-30d In Cardiomyocytes With Afmentioning

confidence: 99%

Atrial Fibrillation-Mediated Upregulation of miR-30d Regulates Myocardial Electrical Remodeling of the G-Protein-Gated K+ Channel, IK.ACh

Miyamoto

Iwata

Nakada

et al. 2016

Circ J

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“…In the former, AGEs exert bad effects via cross linking of important proteins. On the other hand, AGEs bind to RAGE, thereby inducing oxidative stress [ 18 , 36 , 37 , 38 , 39 ], leading to K v channel impairment and vascular damage [ 6 , 40 , 41 , 42 ]. Therefore, we used anti-RAGE to block AGEs binding with RAGE.…”

Section: Discussionmentioning

confidence: 99%

“…The interaction of AGEs/RAGE can activate a diverse array of intracellular signaling pathways including p21 ras , MAPK, and NF-κB that stimulate oxidative stress [ 18 , 36 , 37 , 38 , 39 ]. Increased oxidative stress has been described to downregulate K v channels both at the protein and mRNA level [ 40 , 41 , 42 ]. In addition, AGEs/RAGE interaction has been shown to downregulate PPARγ, a member of the nuclear hormone receptor superfamily, which was proposed to be a regulator of transcriptional regulation of K v channel expression in retinal arterioles [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Advanced Glycation End Products Impair Voltage-Gated K+ Channels-Mediated Coronary Vasodilation in Diabetic Rats

Chen

et al. 2015

PLoS ONE

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BackgroundWe have previously reported that high glucose impairs coronary vasodilation by reducing voltage-gated K+ (Kv) channel activity. However, the underlying mechanisms remain unknown. Advanced glycation end products (AGEs) are potent factors that contribute to the development of diabetic vasculopathy. The aim of this study was to investigate the role of AGEs in high glucose-induced impairment of Kv channels-mediated coronary vasodilation.MethodsPatch-clamp recording and molecular biological techniques were used to assess the function and expression of Kv channels. Vasodilation of isolated rat small coronary arteries was measured using a pressurized myograph. Treatment of isolated coronary vascular smooth muscle cells (VSMCs) and streptozotocin-induced diabetic rats with aminoguanidine, the chemical inhibitor of AGEs formation, was performed to determine the contribution of AGEs.ResultsIncubation of VSMCs with high glucose reduced Kv current density by 60.4 ± 4.8%, and decreased expression of Kv1.2 and Kv1.5 both at the gene and protein level, whereas inhibiting AGEs formation or blocking AGEs interacting with their receptors prevented high glucose-induced impairment of Kv channels. In addition, diabetic rats manifested reduced Kv channels-mediated coronary dilation (9.3 ± 1.4% vs. 36.9 ± 1.4%, P < 0.05), which was partly corrected by the treatment with aminoguanidine (24.4 ± 2.2% vs. 9.3 ± 1.4%, P < 0.05).ConclusionsExcessive formation of AGEs impairs Kv channels in VSMCs, then leading to attenuation of Kv channels-mediated coronary vasodilation.

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Cardiomyocyte-Derived Mitochondrial Superoxide Causes Myocardial Electrical Remodeling by Downregulating Potassium Channels and Related Molecules

Cited by 15 publications

References 33 publications

Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels

Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels

Atrial Fibrillation-Mediated Upregulation of miR-30d Regulates Myocardial Electrical Remodeling of the G-Protein-Gated K<sup>+</sup> Channel, <i>I</i><sub>K.ACh</sub>

Advanced Glycation End Products Impair Voltage-Gated K+ Channels-Mediated Coronary Vasodilation in Diabetic Rats

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