TY - JOUR
T1 - The toll of the gridiron
T2 - Damage-associated molecular patterns and hypertension in American football
AU - McCarthy, Cameron G.
AU - Webb, R. Clinton
N1 - Funding Information:
The authors thank Drs. T. Szasz and C. F. Wenceslau (Department of Physiology, Georgia Regents University, Augusta, GA, USA) and Drs. N. Jenkins and K. McCully (Department of Kinesiology, University of Georgia, Athens, GA, USA), for their critical evaluation of the manuscript and editorial expertise. The preparation of this report was supported in part by a predoctoral fellowship (to C.G.M.) and a grant-in-aid (to R.C.W.) from the American Heart Association; U.S. National Institutes of Health (NIH) National Heart, Lung, and Blood Institute Grant R01HL071138 (to R.C.W.); and NIH National Institute of Diabetes and Digestive and Kidney Diseases Grant R01DK083685 (to R.C.W.). The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - American football has unequivocally been linked to elevations in blood pressure and hypertension, especially in linemen. However, the mechanisms of this increase cannot be attributed solely to increased body weight and associated cardiometabolic risk factors (e.g., dyslipidemia or hyperglycemia). Therefore, understanding the etiology of football-associated hypertension is essential for improving the quality of life in this mostly young population, as well as for lowering the potential for chronic disease in the future. We propose that inflammatogenic damage-associated molecular patterns (DAMPs) released into the circulation from football-induced musculoskeletal trauma activate pattern-recognition receptors of the innate immune system - specifically, high mobility group box 1 protein (HMGB1) and mitochondrial (mt)DNA which activate Toll-like receptor (TLR)4 and -9, respectively. Previously, we observed that circulating levels of these 2 DAMPs are increased in hypertension, and activation of TLR4 and -9 causes endothelial dysfunction and hypertension. Therefore, our novel hypothesis is that musculoskeletal injury from repeated hits in football players, particularly in linemen, leads to elevated circulating HMGB1 and mtDNA to activate TLRs on endothelial cells leading to impaired endothelium-dependent vasodilation, increased vascular tone, and hypertension.
AB - American football has unequivocally been linked to elevations in blood pressure and hypertension, especially in linemen. However, the mechanisms of this increase cannot be attributed solely to increased body weight and associated cardiometabolic risk factors (e.g., dyslipidemia or hyperglycemia). Therefore, understanding the etiology of football-associated hypertension is essential for improving the quality of life in this mostly young population, as well as for lowering the potential for chronic disease in the future. We propose that inflammatogenic damage-associated molecular patterns (DAMPs) released into the circulation from football-induced musculoskeletal trauma activate pattern-recognition receptors of the innate immune system - specifically, high mobility group box 1 protein (HMGB1) and mitochondrial (mt)DNA which activate Toll-like receptor (TLR)4 and -9, respectively. Previously, we observed that circulating levels of these 2 DAMPs are increased in hypertension, and activation of TLR4 and -9 causes endothelial dysfunction and hypertension. Therefore, our novel hypothesis is that musculoskeletal injury from repeated hits in football players, particularly in linemen, leads to elevated circulating HMGB1 and mtDNA to activate TLRs on endothelial cells leading to impaired endothelium-dependent vasodilation, increased vascular tone, and hypertension.
KW - Blood pressure
KW - Inflammation
KW - Musculoskeletal trauma
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U2 - 10.1096/fj.15-279588
DO - 10.1096/fj.15-279588
M3 - Article
C2 - 26316270
AN - SCOPUS:84974781451
SN - 0892-6638
VL - 30
SP - 34
EP - 40
JO - FASEB Journal
JF - FASEB Journal
IS - 1
ER -