Novel Role of AT1 Receptor in Heart Failure and the Significance of Oxidative Stress

2006 ◽  
Vol 12 (8) ◽  
pp. S152
Author(s):  
Shokei Kim-Mitsuyama ◽  
Eiichiro Yamamoto
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
At1 Receptor

Role of oxidative stress in left ventricular remodeling and heart failure after myocardial infarction

1999 ◽  
Vol 5 (3) ◽  
pp. 79
Author(s):  
Shintaro Kinugawa ◽  
Hiroyuki Tsutsui ◽  
Tomomi Ide ◽  
Hideo Ustumi ◽  
Nobuhiro Suematsu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular

Abstract 125: Perturbation of Mitochondrial Calcium Uniporter Promotes Cardiac Oxidative Stress and Autophagy During Heart Failure

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sudarsan Rajan ◽  
Santhanam Shanmughapriya ◽  
Dhanendra Tomar ◽  
Zhiwei Dong ◽  
Joseph Y Cheung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Mouse Model ◽  
Atp Depletion ◽  
Regulatory Role ◽  
Mitochondrial Calcium ◽  
Mitochondrial Bioenergetics ◽  
Complex Assembly ◽  
New Findings

Mitochondrial calcium ([Ca 2+ ] m ) is essential for cardiomyocyte viability, and aberration of [Ca 2+ ] m is known to elicit multiple cardiac stress conditions associated with ATP depletion, reactive oxygen species, and mitochondrial permeability transition pore opening, all of which can lead to metabolic stress and the loss of dysfunctional mitochondria by aberrant autophagy. Elucidating the regulatory role of m itochondrial c alcium u niporter (MCU)-mediated [Ca 2+ ] m in modulating cardiac mitochondrial bioenergetics and autophagy has high significance and clinical impact for many pathophysiological processes. [Ca 2+ ] m is exquisitely controlled by the inner mitochondrial membrane uniporter, transporters, regulators and exchangers including MCU, MCUR1, EMRE, MICU1, MICU2 and LETM1. Our recently published findings revealed that Mitochondrial Ca 2+ Uniporter Regulator 1 (MCUR1) serves as a scaffold factor for uniporter complex assembly. We found that deletion of MCUR1 impaired [Ca 2+ ] m uptake, mitochondrial Ca 2+ current ( I MCU ) and mitochondrial bioenergetics and is associated with increased autophagy. Our new findings indicate that the impairment of [Ca 2+ ] m uptake exacerbated autophagy following ischemia-reperfusion (I/R) injury. In support of our mouse model, human failing hearts show that MCUR1 protein levels are markedly decreased and autophagy markers are increased, demonstrating a crucial link between [Ca 2+ ] m uptake and autophagy during heart failure. Additionally, our results reveal that either oxidation or disruption of human MCU Cys-97 (in mouse Cys-96; gain-of-function MCU C96A mutant) produces a conformational change within the N terminal β-grasp fold of MCU which promotes higher-order MCU complex assembly and increased I MCU activity and mitochondrial ROS levels. The results of our studies using a novel cardiac-specific MCUR1-KO model and a constitutively active global MCU C96A KI mouse model (CRISPR-Cas9 genome edited) elucidate the regulatory role of [Ca 2+ ] m in cardiac bioenergetics and autophagy during oxidative stress and myocardial infarction. Thus, targeting assembly and the activity of MCU complex will offer a new potential therapeutic target in the treatment of cardiomyopathy and heart failure.

scholarly journals Role of Oxidative Stress in Heart Failure: Insights from Gene Transfer Studies

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1645
Author(s):  
Bart De Geest ◽  
Mudit Mishra
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Gene Therapy ◽  
Steady State ◽  
Gene Transfer ◽  
Oxidative Modification ◽  
Heme Oxygenase 1 ◽  
Therapy Studies ◽  
Pathological Remodeling

Under physiological circumstances, there is an exquisite balance between reactive oxygen species (ROS) production and ROS degradation, resulting in low steady-state ROS levels. ROS participate in normal cellular function and in cellular homeostasis. Oxidative stress is the state of a transient or a persistent increase of steady-state ROS levels leading to disturbed signaling pathways and oxidative modification of cellular constituents. It is a key pathophysiological player in pathological hypertrophy, pathological remodeling, and the development and progression of heart failure. The heart is the metabolically most active organ and is characterized by the highest content of mitochondria of any tissue. Mitochondria are the main source of ROS in the myocardium. The causal role of oxidative stress in heart failure is highlighted by gene transfer studies of three primary antioxidant enzymes, thioredoxin, and heme oxygenase-1, and is further supported by gene therapy studies directed at correcting oxidative stress linked to metabolic risk factors. Moreover, gene transfer studies have demonstrated that redox-sensitive microRNAs constitute potential therapeutic targets for the treatment of heart failure. In conclusion, gene therapy studies have provided strong corroborative evidence for a key role of oxidative stress in pathological remodeling and in the development of heart failure.

scholarly journals Role of Oxidant Stress on AT1 Receptor Expression in Neurons of Rabbits With Heart Failure and in Cultured Neurons

2008 ◽  
Vol 103 (2) ◽  
pp. 186-193 ◽  
Author(s):  
Dongmei Liu ◽  
Lie Gao ◽  
Shyamal K. Roy ◽  
Kurtis G. Cornish ◽  
Irving H. Zucker
Keyword(s):  
Heart Failure ◽  
Oxidant Stress ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Cultured Neurons

scholarly journals Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications

2015 ◽  
Vol 36 (38) ◽  
pp. 2555-2564 ◽  
Author(s):  
Thomas Münzel ◽  
Tommaso Gori ◽  
John F. Keaney ◽  
Christoph Maack ◽  
Andreas Daiber
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Diastolic Heart Failure ◽  
Therapeutic Implications ◽  
Pathophysiological Role

scholarly journals Role of CyPA in cardiac hypertrophy and remodeling

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Mengfei Cao ◽  
Wei Yuan ◽  
Meiling Peng ◽  
Ziqi Mao ◽  
Qianru Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Interstitial Fibrosis ◽  
Systolic Function ◽  
Cardiac Fibroblasts ◽  
Cardiomyocyte Hypertrophy ◽  
Pathological Cardiac Hypertrophy ◽  
Complex Process

Abstract Pathological cardiac hypertrophy is a complex process and eventually develops into heart failure, in which the heart responds to various intrinsic or external stress, involving increased interstitial fibrosis, cell death and cardiac dysfunction. Studies have shown that oxidative stress is an important mechanism for this maladaptation. Cyclophilin A (CyPA) is a member of the cyclophilin (CyPs) family. Many cells secrete CyPA to the outside of the cells in response to oxidative stress. CyPA from blood vessels and the heart itself participate in a variety of signaling pathways to regulate the production of reactive oxygen species (ROS) and mediate inflammation, promote cardiomyocyte hypertrophy and proliferation of cardiac fibroblasts, stimulate endothelial injury and vascular smooth muscle hyperplasia, and promote the dissolution of extracellular matrix (ECM) by activating matrix metalloproteinases (MMPs). The events triggered by CyPA cause a decline of diastolic and systolic function and finally lead to the occurrence of heart failure. This article aims to introduce the role and mechanism of CyPA in cardiac hypertrophy and remodeling, and highlights its potential role as a disease biomarker and therapeutic target.

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