Nitric Oxide Synthases in Heart Failure

Carnicer, Ricardo; Crabtree, Mark J.; Sivakumaran, Vidhya; Casadei, Barbara; Kass, David A.

doi:10.1089/ars.2012.4824

Cited by 150 publications

(153 citation statements)

References 271 publications

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“…All NOSs generate NO and S-nitrosothiols (SNO) (68). NO primarily functions to stimulate soluble guanylate cyclase to produce cyclic guanosine monophosphate (cGMP), which has numerous downstream targets through cGMP-dependent kinases and phosphodiesterases (9). NO also readily reacts with superoxide to form perioxynitrite (NO + O 2 -/ONOO -), which, in turn, reacts potently with thiol groups to S-nitrosylate-specific protein targets.…”

Section: Nitric Oxidementioning

confidence: 99%

Mechanical Stretch-Induced Activation of ROS/RNS Signaling in Striated Muscle

Ward

Prosser²,

Lederer³

2014

Antioxidants & Redox Signaling

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Significance: Mechanical activation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) occurs in striated muscle and affects Ca 2+ signaling and contractile function. ROS/RNS signaling is tightly controlled, spatially compartmentalized, and source specific. Recent Advances: Here, we review the evidence that within the contracting myocyte, the trans-membrane protein NADPH oxidase 2 (Nox2) is the primary source of ROS generated during contraction. We also review a newly characterized signaling cascade in cardiac and skeletal muscle in which the microtubule network acts as a mechanotransduction element that activates Nox2-dependent ROS generation during mechanical stretch, a pathway termed X-ROS signaling. Critical Issues: In the heart, X-ROS acts locally and affects the sarcoplasmic reticulum (SR) Ca 2+ release channels (ryanodine receptors) and tunes Ca 2+ signaling during physiological behavior, but excessive X-ROS can promote Ca 2+ -dependent arrhythmias in pathology. In skeletal muscle, X-ROS sensitizes Ca 2+ -permeable sarcolemmal ''transient receptor potential'' channels, a pathway that is critical for sustaining SR load during repetitive contractions, but when in excess, it is maladaptive in diseases such as Duchenne Musclar dystrophy. Future Directions: New advances in ROS/RNS detection as well as molecular manipulation of signaling pathways will provide critical new mechanistic insights into the details of X-ROS signaling. These efforts will undoubtedly reveal new avenues for therapeutic intervention in the numerous diseases of striated muscle in which altered mechanoactivation of ROS/RNS production has been identified. Antioxid. Redox Signal. 20,[929][930][931][932][933][934][935][936]

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Section: Nitric Oxidementioning

confidence: 99%

Mechanical Stretch-Induced Activation of ROS/RNS Signaling in Striated Muscle

Ward

Prosser²,

Lederer³

2014

Antioxidants & Redox Signaling

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“…These NOS isoforms are localized to different microdomains in the cardiomyocytes, and are linked to selective signaling that is further impacted by heart disease. For instance, while eNOS is involved with cGMPdependent modulation of β-adrenergic stimuli, nNOS is linked to sarcoplasmic reticular calcium cycling (the reader is kindly directed to specific reviews on this topic) [24,34,128,190]. In this context, it is useful to recall that iNOS may play a protective role in the so called second window of protection of preconditioning [22,121,149] A Under stress conditions, eNOS translocates from the sarcolemma to the mitochondria [209] with an essential role of lipid rafts [51] or signalosomes [176].…”

Section: In Cardiomyocytes the Principal Source Of Ros Is The Mitochomentioning

confidence: 99%

Redox balance and cardioprotection

et al. 2013

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Coronary artery disease is a major cause of morbidity and mortality in the Western countries. Acute myocardial infarction is a serious and often lethal consequence of coronary artery disease, resulting in contractile dysfunction and cell death. It is well known that unbalanced and high steady state levels of reactive oxygen and nitrogen species (ROS/RNS) are responsible of cytotoxicity, which in heart leads to contractile dysfunction and cell death. Pre-and post-conditioning of the myocardium are two treatment strategies that reduce contractile dysfunction and the amount of cell death considerably. Paradoxically, ROS and RNS have been identified as a part of cardioprotective signaling molecules, which are essential in pre-and post-conditioning processes. S-nitrosylation of proteins is a specific posttranslational modification that plays an important role in cardioprotection, especially within mitochondria. In fact, mitochondria are of paramount importance in either promoting or limiting ROS/RNS generation and reperfusion injury, and in triggering kinase activation by ROS/RNS-signaling in cardioprotection. These organelles are also the targets of acidosis, which prevent mitochondrial transition pore opening, thus avoiding ROS induced ROS release. Therefore we will consider mitochondria as either targets of damage or protection from it. The origin of ROS/RNS and the cardioprotective signaling pathways involved in ROS/RNS-based pre-and post-conditioning will be explored in this article. A particular emphasis will be given to new aspects concerning the processes of S-nitrosylation in the cardioprotective scenario.

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“…There are three NOS isoforms: NOS1 or neuronal NOS (nNOS); NOS2 or inducible NOS (iNOS); and NOS3 or endothelial NOS (eNOS), two of which (nNOS and eNOS) are constitutively expressed in the cardiovascular system (27). Under physiological conditions, NO generated by NOSs in a tightly regulated manner participates in several cellular signaling pathways.…”

Section: What Is the Role Of Myocardial Endogenous Oxidase Systems Inmentioning

confidence: 99%

Targeting Inflammation and Oxidative Stress in Atrial Fibrillation: Role of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibition with Statins

Pinho-Gomes

Reilly

Brandes

et al. 2014

Antioxidants & Redox Signaling

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Significance: Atrial fibrillation (AF) is a burgeoning health-care problem, and the currently available therapeutic armamentarium is barely efficient. Experimental and clinical evidence implicates inflammation and myocardial oxidative stress in the pathogenesis of AF. Recent Advances: Local and systemic inflammation has been found to both precede and follow the new onset of AF, and NOX2-dependent generation of reactive oxygen species in human right atrial samples has been independently associated with the occurrence of AF in the postoperative period in patients undergoing cardiac surgery. Anti-inflammatory and antioxidant agents can prevent atrial electrical remodeling in animal models of atrial tachypacing and the new onset of AF after cardiac surgery, suggesting a causal relationship between inflammation/oxidative stress and the atrial substrate that supports AF. Critical Issues: Statin therapy, by redressing the myocardial nitroso-redox balance and reducing inflammation, has emerged as a potentially effective strategy for the prevention of AF. Evidence indicates that statins prevent AF-induced electrical remodeling in animal models of atrial tachypacing and may reduce the new onset of AF after cardiac surgery. However, whether statins have antiarrhythmic properties in humans has yet to be conclusively demonstrated, as data from randomized controlled trials specifically addressing the relevance of statin therapy for the primary and secondary prevention of AF remain scanty. Future Directions: A better understanding of the mechanisms underpinning the putative antiarrhythmic effects of statins may afford tailoring AF treatment to specific clinical settings and patient's subgroups. Large-scale randomized clinical trials are needed to support the indication of statin therapy solely on the basis of AF prevention. Antioxid. Redox Signal. 20, 1268Signal. 20, -1285

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Nitric Oxide Synthases in Heart Failure

Cited by 150 publications

References 271 publications

Mechanical Stretch-Induced Activation of ROS/RNS Signaling in Striated Muscle

Mechanical Stretch-Induced Activation of ROS/RNS Signaling in Striated Muscle

Redox balance and cardioprotection

Targeting Inflammation and Oxidative Stress in Atrial Fibrillation: Role of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibition with Statins

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