The toll of the gridiron: damage‐associated molecular patterns and hypertension in American football

McCarthy, Cameron G.; Webb, R. Clinton

doi:10.1096/fj.15-279588

Cited by 20 publications

(16 citation statements)

References 54 publications

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“…TLR-4, which is expressed on monocytes [68], has been shown to induce NET formation [63]. Apart from lipopolysaccharide, TLR-4 recognizes a variety of danger-associated molecular patterns, including high mobility group box 1 (HMGB1) [65], which is a component and important inducer of NETs [40, 42]. Addition of an anti-TLR-4 blocking antibody exerted a similarly inhibitory effect as DNase treatment.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil extracellular traps and fibrocytes in ST-segment elevation myocardial infarction

et al. 2019

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Leukocyte-mediated inflammation is central in atherothrombosis and ST-segment elevation myocardial infarction (STEMI). Neutrophil extracellular traps (NETs) have been shown to enhance atherothrombosis and stimulate fibroblast function. We analyzed the effects of NETs on cardiac remodeling after STEMI. We measured double-stranded (ds)DNA and citrullinated histone H3 (citH3) as NET surrogate markers in human culprit site and femoral blood collected during primary percutaneous coronary intervention ( n = 50). Fibrocytes were characterized in whole blood by flow cytometry, and in culprit site thrombi and myocardium by immunofluorescence. To investigate mechanisms of fibrocyte activation, isolated NETs were used to induce fibrocyte responses in vitro. Enzymatic infarct size was assessed using creatine-phosphokinase isoform MB area under the curve. Left ventricular function was measured by transthoracic echocardiography. NET surrogate markers were increased at the culprit site compared to the femoral site and were positively correlated with infarct size and left ventricular dysfunction at follow-up. In vitro, NETs promoted fibrocyte differentiation from monocytes and induced fibrocyte activation. Highly activated fibrocytes accumulated at the culprit site and in the infarct transition zone. Our data suggest that NETs might be important mediators of fibrotic remodeling after STEMI, possibly by stimulating fibrocytes. Electronic supplementary material The online version of this article (10.1007/s00395-019-0740-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Neutrophil extracellular traps and fibrocytes in ST-segment elevation myocardial infarction

et al. 2019

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“…Subsequent studies have confirmed a similar increase in heart disease mortality in active and former ASF linemen as well as a higher risk of metabolic syndrome and subclinical carotid atherosclerosis (11,29,30). While elevated body mass has been proposed as a key explanatory factor, this parameter unlikely explains the complete mechanistic story (10,31). Data from the current study introduce a more comprehensive mechanistic explanation in the form of acquired, early-life hypertension with resultant target organ damage in the form of concentric LV hypertrophy with subclinical LV systolic dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Blood Pressure and LV Remodeling Among American-Style Football Players

Lin

Wang

Weiner

et al. 2016

JACC: Cardiovascular Imaging

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Objective To determine the relationships between American style football (ASF) participation, acquired left ventricular (LV) hypertrophy, and LV systolic function as assessed using contemporary echocardiographic parameters. Background Participation in ASF has been associated with the development of hypertension and LV hypertrophy. To what degree these processes impact LV function is unknown. Methods This is a prospective, longitudinal, cohort study evaluating NCAA Division I collegiate football athletes stratified by field position (linemen, n=30 vs. non-linemen, n=57) before and after a single competitive season with transthoracic echocardiography. LV systolic function was measured using complementary parameters of global longitudinal strain (GLS, 2D speckle-tracking) and ejection fraction (EF, 2D biplane). Results ASF participation was associated with field position-specific increases in systolic blood pressure (linemen Δ SBP = 10±8 mmHg vs. non-linemen Δ SBP = 3±7 mmHg, p<0.001) and an overall increase in incident LV hypertrophy (pre = 8% vs. post = 25%, p<0.05). Linemen who developed LV hypertrophy had concentric geometry (9/11, 82%) with decreased GLS (Δ = −1.1%, p<0.001) while non-linemen demonstrated eccentric LV hypertrophy (8/10, 80%) with increased GLS (Δ = +1.4%, p<0.001). In contrast, LV ejection fraction in the total cohort and when stratified by field position was not significantly affected by ASF participation. Among the total cohort, lineman field position, postseason weight, systolic blood pressure, average LV wall thickness, and relative wall thickness were all independent predictors of postseason GLS. Conclusions ASF participation at a lineman field position may lead to a form of sport-related myocardial remodeling that is pathologic rather than adaptive. Future study will be required to determine if targeted efforts to control blood pressure, minimize weight gain, and to include an element of aerobic conditioning in this subset of athletes may attenuate this process and translate into tangible downstream health benefits.

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“…Diabetes causes increased serum levels of high mobility group-B1 (HMGB1) [60] , a known DAMP [31] that activates TLR4 [31] , which would be expected to enhance inflammation. Similarly, in some cases hypertension has also been proposed to result from enhanced serum DAMP levels (reviewed in [61] ), which again could possibly lead to a chronic low-level inflammation. Obesity is also thought to be accompanied by inflammation (reviewed in [62] ).…”

Section: Additional Considerationsmentioning

confidence: 99%

Phosphatidylglycerol and surfactant: A potential treatment for COVID-19?

Bollag

Gonzales

2020

Medical Hypotheses

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A hypothesis concerning the potential utility of surfactant supplementation for the treatment of critically ill patients with COVID-19 is proposed, along with a brief summary of the data in the literature supporting this idea. It is thought that surfactant, which is already approved by the Food and Drug Administration for intratracheal administration to treat neonatal respiratory distress syndrome in pre-term infants, could benefit COVID-19-infected individuals by: (1) restoring surfactant damaged by lung infection and/or decreased due to the virus-induced death of the type II pneumocytes that produce it and (2) reducing surface tension to decrease the work of breathing and limit pulmonary edema. In addition, a constituent of surfactant, phosphatidylglycerol, could mitigate COVID-19-induced lung pathology by: (3) decreasing excessive innate immune system stimulation via its inhibition of toll-like receptor-2 and -4 activation by microbial components and cellular proteins released by damaged cells, thereby limiting inflammation and the resultant pulmonary edema, and (4) possibly blocking spread of the viral infection to non-infected cells in the lung. Therefore, it is suggested that surfactant preparations containing phosphatidylglycerol be tested for their ability to improve lung function in critically ill patients with COVID-19.

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The toll of the gridiron: damage‐associated molecular patterns and hypertension in American football

Cited by 20 publications

References 54 publications

Neutrophil extracellular traps and fibrocytes in ST-segment elevation myocardial infarction

Neutrophil extracellular traps and fibrocytes in ST-segment elevation myocardial infarction

Blood Pressure and LV Remodeling Among American-Style Football Players

Phosphatidylglycerol and surfactant: A potential treatment for COVID-19?

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