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

Systolic and diastolic myocardial dysfunction has been demonstrated to be associated with an activation of the circulating and local renin-angiotensin-aldosterone system (RAAS), and with a subsequent inappropriately increased production of reactive oxygen species (ROS). While, at low concentrations,...

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Bibliographic Details
Published in:European heart journal Vol. 36; no. 38; pp. 2555 - 2564
Main Authors: Münzel, Thomas, Gori, Tommaso, Keaney, Jr, John F, Maack, Christoph, Daiber, Andreas
Format: Journal Article
Language:English
Published: England 07.10.2015
Subjects:
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Antioxidants - therapeutic use
Cardiovascular System - enzymology
Cardiovascular System - metabolism
Drug Therapy, Combination
Exercise Therapy - methods
Heart Failure, Diastolic - etiology
Heart Failure, Systolic - enzymology
Heart Failure, Systolic - etiology
Humans
Hydralazine - therapeutic use
Mitochondria - metabolism
NADPH Oxidases - physiology
Nitrates - therapeutic use
Nitric Oxide - deficiency
Nitric Oxide Synthase - physiology
Oxidative Stress - physiology
Phosphodiesterase Inhibitors - therapeutic use
Reactive Oxygen Species - chemistry
Reactive Oxygen Species - metabolism
Stroke Volume - physiology
Vitamins - therapeutic use
Xanthine Oxidase - physiology
ISSN:1522-9645
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Summary:Systolic and diastolic myocardial dysfunction has been demonstrated to be associated with an activation of the circulating and local renin-angiotensin-aldosterone system (RAAS), and with a subsequent inappropriately increased production of reactive oxygen species (ROS). While, at low concentrations, ROS modulate important physiological functions through changes in cellular signalling and gene expression, overproduction of ROS may adversely alter cardiac mechanics, leading to further worsening of systolic and diastolic function. In addition, vascular endothelial dysfunction due to uncoupling of the nitric oxide synthase, activation of vascular and phagocytic membrane oxidases or mitochondrial oxidative stress may lead to increased vascular stiffness, further compromising cardiac performance in afterload-dependent hearts. In the present review, we address the potential role of ROS in the pathophysiology of myocardial and vascular dysfunction in heart failure (HF) and their therapeutic targeting. We discuss possible mechanisms underlying the failure of antioxidant vitamins in improving patients' prognosis, the impact of angiotensin-converting enzyme inhibitors or AT1 receptor blockers on oxidative stress, and the mechanism of the benefit of combination of hydralazine/isosorbide dinitrate. Further, we provide evidence supporting the existence of differences in the pathophysiology of HF with preserved vs. reduced ejection fraction and whether targeting mitochondrial ROS might be a particularly interesting therapeutic option for patients with preserved ejection fraction.
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ISSN:1522-9645
DOI:10.1093/eurheartj/ehv305