Chronic xanthine oxidase inhibition prevents myofibrillar protein oxidation and preserves cardiac function in a transgenic mouse model of cardiomyopathy

Duncan, Jennifer G.; Ravi, Rajashree; Stull, Linda B.; Murphy, Anne M.

doi:10.1152/ajpheart.00168.2005

Cited by 52 publications

(44 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Curved arrow depicts the steeper end-systolic pressurevolume relationship in heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction Striated muscle is subjected to oxidative stress and evidence now suggests that oxidative stress also modulates contractile function in cardiac and skeletal muscle. Redox modifications of proteins are known to result in functionally important changes in protein structure, stability, interactivity, and activity (Haycock et al 1996;Posterino and Lamb 1996;Gao et al 1996;Disatnik et al 1998;Duncan et al 2005;Dai et al 2007;Sanchez et al 2008;Ullrich et al 2009;Canton et al 2014). However, due to the limited data available and the fact that most studies have focused mainly on post-translational modifications of single purified contractile proteins, our understanding of the redox-dependent mechanisms that control contraction-relaxation in the intact heart remains poor.…”

Section: Structural Elements Contributing To Myocardial Passive Stiffmentioning

confidence: 99%

“…Oxidative stress can result in direct chemical oxidation of proteins, leading to changes in their structure, function and activity. In addition, it induces subtle changes in intracellular pathways and redox signalling that cause cellular dysfunction and damage (Haycock et al 1996;Disatnik et al 1998;Duncan et al 2005;Dai et al 2007;Canton et al 2014) (Fig. 3).…”

Section: Structural Elements Contributing To Myocardial Passive Stiffmentioning

confidence: 99%

“…Several antioxidants are known to ameliorate the progress of HF (Takimoto and Kass 2007), and chronic inhibition of xanthine oxidase (XO) has been shown to preserve cardiac function in a transgenic mouse (Duncan et al 2005). Donors of nitroxyl, the reduced congener of NO, were also able to increase force development in intact rat trabeculae (Dai et al 2007).…”

Section: Structural Elements Contributing To Myocardial Passive Stiffmentioning

confidence: 99%

“…While recent evidence indicates a role for oxidative and nitrosative regulation of the Ca 2+ -sensitive proteome in excitation-contraction (EC) coupling, only phosphorylation is the best-established therapeutic target (Haycock et al 1996;Posterino and Lamb 1996;Gao et al 1996;Disatnik et al 1998;Duncan et al 2005;Dai et al 2007;Ullrich et al 2009;Canton et al 2014).…”

Section: Titin As a Potential Biomarker In Chagas' Diseasementioning

confidence: 99%

See 3 more Smart Citations

A change of heart: oxidative stress in governing muscle function?

Breitkreuz

Hamdani

2015

Biophys Rev

View full text Add to dashboard Cite

Redox/cysteine modification of proteins that regulate calcium cycling can affect contraction in striated muscles. Understanding the nature of these modifications would present the possibility of enhancing cardiac function through reversible cysteine modification of proteins, with potential therapeutic value in heart failure with diastolic dysfunction. Both heart failure and muscular dystrophy are characterized by abnormal redox balance and nitrosative stress. Recent evidence supports the synergistic role of oxidative stress and inflammation in the progression of heart failure with preserved ejection fraction, in concert with endothelial dysfunction and impaired nitric oxide-cyclic guanosine monophosphate-protein kinase G signalling via modification of the giant protein titin. Although antioxidant therapeutics in heart failure with diastolic dysfunction have no marked beneficial effects on the outcome of patients, it, however, remains critical to the understanding of the complex interactions of oxidative/nitrosative stress with pro-inflammatory mechanisms, metabolic dysfunction, and the redox modification of proteins characteristic of heart failure. These may highlight novel approaches to therapeutic strategies for heart failure with diastolic dysfunction. In this review, we provide an overview of oxidative stress and its effects on pathophysiological pathways. We describe the molecular mechanisms driving oxidative modification of proteins and subsequent effects on contractile function, and, finally, we discuss potential therapeutic opportunities for heart failure with diastolic dysfunction.

show abstract

Section: Structural Elements Contributing To Myocardial Passive Stiffmentioning

confidence: 99%

Section: Structural Elements Contributing To Myocardial Passive Stiffmentioning

confidence: 99%

Section: Structural Elements Contributing To Myocardial Passive Stiffmentioning

confidence: 99%

Section: Titin As a Potential Biomarker In Chagas' Diseasementioning

confidence: 99%

See 2 more Smart Citations

A change of heart: oxidative stress in governing muscle function?

Breitkreuz

Hamdani

2015

Biophys Rev

View full text Add to dashboard Cite

show abstract

“…Several antioxidants have been shown to ameliorate the progress of heart failure in animals as well as in patients (reviewed in [106]). For example, chronic xanthine oxidase inhibition preserved cardiac function in a transgenic mouse model of cardiomyopathy, and interestingly, myofibrillar protein oxidation was reduced in this disease model as well [109]. Myofilament proteins were also believed to be the target of nitrosylation as detergent-skinned ventricular trabeculae showed impaired contraction in the presence of peroxynitrate at physiological concentration [110].…”

Section: Oxidation and Nitrosylationmentioning

confidence: 94%

Myofilament proteins: From cardiac disorders to proteomic changes

Yuan

Solaro

2008

Proteomics Clinical Apps

View full text Add to dashboard Cite

Myofilament proteins of the cardiac sarcomere house the molecular machinery responsible for generating tension and pressure. Release of intracellular Ca 21 triggers myofilament tension generation and shortening, but the response to Ca 21 is modulated by changes in key regulatory proteins. We review how these proteomic changes are essential to adaptive physiological regulation of cardiac output and become maladaptive in cardiac disorders. We also review the essentials of proteomic techniques used to study myofilament protein changes, including degradation, isoform expression, phosphorylation and oxidation. Selected proteomic studies illustrate the applications of these approaches.

show abstract

Hyperuricemia treatment in acute heart failure patients does not improve their long‐term prognosis: A propensity score matched analysis from the AHEAD registry

Pavlušová

Jarkovský

Benešová

et al. 2019

Clinical Cardiology

View full text Add to dashboard Cite

Background Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients. Methods The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 μmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two‐ and five‐year all‐cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and/or beta‐blockers. Results In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5‐year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non‐hyperuricemia group and P = 0.073 vs untreated group). Conclusion Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients.

show abstract

Chronic xanthine oxidase inhibition prevents myofibrillar protein oxidation and preserves cardiac function in a transgenic mouse model of cardiomyopathy

Abstract: . Chronic xanthine oxidase inhibition prevents myofibrillar protein oxidation and preserves cardiac function in a transgenic mouse model of cardiomyopathy.

Cited by 52 publications

References 36 publications

A change of heart: oxidative stress in governing muscle function?

A change of heart: oxidative stress in governing muscle function?

Myofilament proteins: From cardiac disorders to proteomic changes

Hyperuricemia treatment in acute heart failure patients does not improve their long‐term prognosis: A propensity score matched analysis from the AHEAD registry

Contact Info

Product

Resources

About