Expression of Rho Kinase and Its Mechanism in the Left Atrial Appendage in Patients with Atrial Fibrillation

Chen, Yongqing; Su, Fangju; Han, Juanping; Jiao, Piqi; Guo, Wenyun

doi:10.1532/hsf.1851

Cited by 7 publications

(8 citation statements)

References 14 publications

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“…Recently, the involvement of the ROCK pathway was documented using left atrial appendage biopsies of AF patients vs. those with sinus rhythm which showed increased expression of ROCK and MYPT-1 that correlated with the expression of Cx40, an integral membrane protein of heart gap junctions, fundamental for the rapid cell-cell transfer of action potential [10].…”

Section: Discussionmentioning

confidence: 99%

“…This last finding then raised questions as to the exact role(s) of the RhoA/ROCK pathway of Ang II transduction in the molecular mechanisms linked to AF. Just recently, Chen et al [10] using human left atrial appendages from patients undergoing cardiac surgery found an overexpression of ROCK, its metabolic downstream mediator myosin phosphatase target subunit-1 (MYPT-1), known as the marker of ROCK activity, as well as Cx40 in those patients with documented AF.…”

Section: Introductionmentioning

confidence: 99%

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Rho Kinase Activity, Connexin 40, and Atrial Fibrillation: Mechanistic Insights from End-Stage Renal Disease on Dialysis Patients

Calò

Ravarotto

Bertoldi

et al. 2020

JCM

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Evidence on cellular/molecular mechanisms leading to atrial fibrillation (AF) are scanty. Increased expression of Rho kinase (ROCK) and myosin-phosphatase-target subunit-1 (MYPT-1), ROCK activity’s marker, were shown in AF patients, which correlated with connexin 40 (Cx40) expression, membrane protein of heart gap junctions, key for rapid action potential’s cell–cell transfer. AF is the most frequent arrhythmia in dialysis patients who present increased MYPT-1 phosphorylation, which correlates with left ventricular (LV) mass. Given ROCK’s established role in cardiovascular–renal remodeling, induction of impaired cell-to-cell coupling/potential conduction promoting AF initiation/perpetuation, we evaluated in dialysis patients with AF, MYPT-1 phosphorylation, Cx40 expression, and their relationships to support their involvement in AF. Mononuclear cells’ MYPT-1 phosphorylation, Cx40 expression, and the ROCK inhibitor fasudil’s effect were assessed in dialysis patients with AF (DPAFs), dialysis patients with sinus rhythm (DPs), and healthy subjects (C) (western blot). M-mode echocardiography assessed LV mass and left atrial systolic volume. DPAF’s phospho-MYPT-1 was increased vs. that of DPs and C (1.57 ± 0.17 d.u. vs. 0.69 ± 0.04 vs. 0.51 ± 0.05 respectively, p < 0.0001). DP’s phospho-MYPT-1 was higher vs. that of C, p = 0.009. DPAF’s Cx40 was higher vs. that of DPs and C (1.23 ± 0.12 vs. 0.74 ± 0.03 vs. 0.69 ± 0.03, p < 0.0001). DPAF’s phospho-MYPT-1 correlated with Cx40 (p < 0.001), left atrial systolic volume (p = 0.013), and LV mass (p = 0.014). In DPAFs, fasudil reduced MYPT-1 phosphorylation (p < 0.01) and Cx40 expression (p = 0.03). These data point toward ROCK and Cx40’s role in the mechanism(s) leading to AF in dialysis patients. Exploration of the ROCK pathway in AF could contribute to AF generation’s mechanistic explanations and likely identify potential pharmacologic targets for translation into treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rho Kinase Activity, Connexin 40, and Atrial Fibrillation: Mechanistic Insights from End-Stage Renal Disease on Dialysis Patients

Calò

Ravarotto

Bertoldi

et al. 2020

JCM

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“…Some athletes may develop an extreme cardiac remodelling process, including atrial structure and function changes [12][13], worse ventricular performance post-effort [6], and appearance of arrhythmias in the long-term follow-up [24]. Regarding the physiopathology of the previous process, the ROCK signaling pathway could play an important role in electrical properties changes in atrial tissue (connexin expression), as Chen et al (2018) showed studying the LA appendage in patients with and without atrial fibrillation [25]. In our study, the HT group showed higher: left cardiac cavities remodelling, ROCK activity and sports performance than other groups; probably these pathways related to cell survival to stress and cardiac remodelling allow to athletes a better adaptation and performance to extreme efforts, but there could be an individual point for each subject in which a poor adaptation may be observed.…”

Section: Discussionmentioning

confidence: 99%

Left Cardiac Remodelling assessed by Echocardiography is Associated with Rho-kinase Activation in Long-distance Runners

Contreras-Briceño¹,

Vega²,

Mandiola³

et al. 2021

Preprint

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This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDR) during the training period before a marathon race. Thirty-six healthy male LDR (37.0±5.3 years; 174.0±7.0 height; BMI: 23.8±2.8; VO2-peak: 56.5±7.3 mL·kg-1·min-1) were separated into two groups according to previous training level: high-training (HT, n=16) ≥100 km·week-1 and low-training (LT, n=20) ≥70 and &lt;100 km·week-1. Also, twenty-one healthy nonactive subjects were included as a control group (CTR). A transthoracic echocardiography was performed and ROCK activity levels in circulating leukocytes were measured at rest (48-hr without exercising) the week before the race. HT group showed higher left ventricular mass index (LVMi) and left atrial volume index (LAVi) than other groups (p&lt;0.05, for both), also higher levels of ROCK activity were found in LDR (HT=6.17±1.41 vs CTR=1.64±0.66 (p&lt;0.01); vs LT=2.74±0.84; (p&lt;0.05)). In LDR a direct correlation between ROCK activity levels and LVMi (r=0.83; p&lt;0.001), and LAVi (r=0.70; p&lt;0.001) were found. In conclusion, in male competitive long-distance runners, the load of exercise implicated in marathon training is associated with ROCK activity levels and the left cardiac remodelling process assessed by echocardiography.

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“…Among the implications of increased left ventricular mass, atrial fibrillation is the most frequent arrhythmia in patients with kidney failure with or without renal replacement therapy and is associated to marked MYPT-1 phosphorylation [68]. Cardiac remodeling, including atrial myocytes structural and electrical alterations, greatly contributes to the pathogenesis of atrial fibrillation.…”

Section: Oxidative Stress and Dialysis Proceduresmentioning

confidence: 99%

The Pivotal Role of Oxidative Stress in the Pathophysiology of Cardiovascular-Renal Remodeling in Kidney Disease

et al. 2021

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The excessive activation of the renin-angiotensin system in kidney disease leads to alteration of intracellular pathways which concur altogether to the induction of cardiovascular and renal remodeling, exposing these patients since the very beginning of the renal injury to chronic kidney disease and progression to end stage renal disease, a very harmful and life threatening clinical condition. Oxidative stress plays a pivotal role in the pathophysiology of renal injury and cardiovascular-renal remodeling, the long-term consequence of its effect. This review will examine the role of oxidative stress in the most significant pathways involved in cardiovascular and renal remodeling with a focus on the detrimental effects of oxidative stress-mediated renal abnormalities on the progression of the disease and of its complications. Food for thoughts on possible therapeutic target are proposed on the basis of experimental evidences.

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Expression of Rho Kinase and Its Mechanism in the Left Atrial Appendage in Patients with Atrial Fibrillation

Cited by 7 publications

References 14 publications

Rho Kinase Activity, Connexin 40, and Atrial Fibrillation: Mechanistic Insights from End-Stage Renal Disease on Dialysis Patients

Rho Kinase Activity, Connexin 40, and Atrial Fibrillation: Mechanistic Insights from End-Stage Renal Disease on Dialysis Patients

Left Cardiac Remodelling assessed by Echocardiography is Associated with Rho-kinase Activation in Long-distance Runners

The Pivotal Role of Oxidative Stress in the Pathophysiology of Cardiovascular-Renal Remodeling in Kidney Disease

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