Tumor Necrosis Factor-α Confers Resistance to Hypoxic Injury in the Adult Mammalian Cardiac Myocyte

Nakano, Masayuki; Knowlton, Anne A; Dibbs, Ziad; Mann, Douglas L.

doi:10.1161/01.cir.97.14.1392

Cited by 130 publications

(84 citation statements)

References 61 publications

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“…Hormonal alterations may play a pivotal role in mediating this process. Inflammatory cytokines are associated with the progression of cardiac hypertrophy,12 and low cytokine levels may be protective for myocytes, whereas persistently high levels are detrimental 13, 14. The growth hormone‐releasing peptide ghrelin has been mainly attributed to the metabolic system and changes in body composition.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex‐DHF pilot study

et al. 2016

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BackgroundOver 50% of patients with symptomatic heart failure (HF) experience HF with preserved ejection fraction (HFpEF). Exercise training (ET) is effective in improving cardiorespiratory fitness and dimensions of quality of life in patients with HFpEF. A systemic pro‐inflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations has been proposed in HFpEF. ET modifies myocardial structure and has been related to inflammatory state. We investigated Ghrelin, related adipokines, markers of inflammation, and neuro‐hormonal activation in patients undergoing a structured ET vs. usual care are with HFpEF. Methods and resultsEx‐DHF‐P was a prospective, controlled, randomized multi‐centre trial on structured and supervised ET in patients with HFpEF. We performed a post hoc analysis in 62 patients from Ex‐DHF‐P. Ghrelin, adiponectin, leptin, IL‐1ß, IL‐6, IL‐10, tumour necrosis factor‐alpha, MR‐proANP, MR‐proADM, CT‐proET1, and CT‐proAVP were assessed to seize the impact of ET on these markers in patients with HFpEF. Thirty‐six (58%) patients were female, mean age was 64 years, and median ghrelin was 928 pg/mL (interquartile range 755–1156). When stratified for high versus low ghrelin, groups significantly differed at baseline in presence obesity, waist circumference, and adiponectin levels (P < 0.05, respectively). Overall, ghrelin levels rose significantly to 1013 pg/mL (interquartile range 813–1182) (P < 0.001). Analysis of covariance modelling for change in ghrelin identified ET (P = 0.013) and higher baseline adiponectin levels (P = 0.035) as influencing factors.ConclusionsExercise training tended to increase ghrelin levels in Ex‐DHF‐P. This increase was especially pronounced in patients with higher baseline adiponectin levels. Future trials are needed to investigate the effect of ET on endogenous ghrelin levels in regard to interactions with cardiac structure and clinically meaningful surrogate parameters.

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Section: Introductionmentioning

confidence: 99%

Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex‐DHF pilot study

et al. 2016

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“…While low levels of cytokines may be protective for myocytes, persistently high levels are detrimental [5,6]. Interleukin (IL)-18 is chronically induced during various immune, infectious, and inflammatory conditions [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload

Colston

Boylston

Feldman

et al. 2007

Biochemical and Biophysical Research Communications

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Interleukin (IL)-18 is a cardiotropic proinflammatory cytokine chronically elevated in the serum of patients with cardiac hypertrophy (LVH). The purpose of this study was to examine the role of IL-18 in pressure-overload hypertrophy using wild type (WT) and IL-18 −/− (null) mice. Adult male C57Bl/ 6 mice underwent transaortic constriction (TAC) for 7 days or sham surgery. Heart weight/body weight ratios showed blunted hypertrophy in IL-18 null TAC mice compared to WT TAC animals. Microarray analyses indicated differential expression of hypertrophy-related genes in WT versus IL-18 nulls. Northern, Western, and EMSA analyses showed Akt and GATA4 were increased in WT but unchanged in IL-18 null mice. Our results demonstrate blunted hypertrophy with reduced expression of contractile-, hypertrophy-, and remodeling-associated genes following pressure overload in IL-18 null mice, and suggest that IL-18 plays a critical role in the hypertrophic response.

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“…For example, application of low concentrations of TNF␣ to isolated adult feline myocytes was shown to confer resistance to hypoxic stress (23). Similarly, when compared with wildtype mice and mice genetically deficient in either Tnfr1 or Tnfr2, mice deficient in both Tnfr1 and Tnfr2 demonstrated both a 40% increase in myocardial infarction size and increased cardiac myocyte apoptosis after ischemia was induced by coronary artery ligation (24).…”

Section: Rationale For Studying Tnf␣ Antagonists In Heart Failurementioning

confidence: 99%

“…TNF␣ production could be an epiphenomenon or could have an adaptive role in heart failure rather than being involved in the pathophysiology of the CHF. Several experimental studies have suggested that physiologic levels of TNF confer cytoprotective responses in the heart during acute ischemic injury (23,24). Moreover, low physiologic levels are likely to play an important role in tissue remodeling and repair (2).…”

Section: Ra and Atherosclerosismentioning

confidence: 99%

Anti–tumor necrosis factor α therapy and heart failure: What have we learned and where do we go from here?

Khanna¹,

McMahon²,

Fürst³

2004

Arthritis & Rheumatism

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Tumor Necrosis Factor-α Confers Resistance to Hypoxic Injury in the Adult Mammalian Cardiac Myocyte

Cited by 130 publications

References 61 publications

Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex‐DHF pilot study

Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex‐DHF pilot study

Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload

Anti–tumor necrosis factor α therapy and heart failure: What have we learned and where do we go from here?

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