Prevalence of abnormal and borderline electrocardiogram changes in 13, 079 Chinese amateur marathon runners.

BACKGROUND: The 12-lead electrocardiogram (ECG) has been adopted as an important component of preparticipation cardiovascular screening. However, there are still controversies in the screening and few studies with a large sample size have reported the results of ECGs of marathon runners. Therefore, the purpose of this study was to assess the prevalence of normal, borderline, and abnormal ECG changes in marathon runners. METHODS: The 12-lead ECG data of 13,079 amateur marathon runners between the ages of 18 and 35 years were included for analysis. The prevalence of ECG abnormalities among different gender groups was compared with chi-square tests. RESULTS: In terms of training-related changes, sinus bradycardia, sinus arrhythmia, and left ventricular high voltage were found in approximately 15, 5, and 3.28% of the participants, respectively. The incidence of right axis deviation in the marathon runners was 1.78%, which was slightly higher than the incidence of left axis deviation (0.88%). No more than 0.1% of the amateur marathon runners exhibited ST-segment depression, T wave inversion (TWI), premature ventricular contraction, pathologic Q waves, and prolonged QT interval. CONCLUSIONS: Training-related ECG changes, including sinus bradycardia, sinus arrhythmia, and left ventricular high voltage, were common in amateur marathon runners. Most abnormal ECG changes, including ST-segment depression, TWI, premature ventricular contraction, pathologic Q waves, and prolonged QT interval, were infrequently found in amateur marathon runners. The data also suggested Chinese amateur marathon runners may have a relatively lower prevalence of ECG abnormalities than black and white runners.

Targeting HMGB1 ameliorates cardiac fibrosis through restoring TLR2-mediated autophagy suppression in myocardial fibroblasts.

BACKGROUND: Extracellular high-mobility group box 1 (HMGB1) has been identified as playing a critical role in the pathogenesis of tissue fibrosis. However, the underlying mechanism of its involvement in cardiac fibrosis is still not well-defined. Here, we aim to investigate whether toll-like receptor 2 (TLR2) contributes to the extracellular HMGB1-mediated development and progression of cardiac fibrosis. METHODS: A mouse model of cardiac fibrosis was induced by subcutaneous injection of isoproterenol (ISO). Glycyrrhizic acid (GA), an inhibitor of HMGB1 derived from natural products, was simultaneously administered by intraperitoneal injection. Echocardiography, H&E and Sirius red staining were used to evaluate cardiac function and fibrosis. The myocardial expression of autophagy-associated proteins was examined using immunoblotting. Cardiac fibroblasts were treated with different concentrations of HMGB1 to examine the expression levels of α-SMA, collagen I and autophagy markers. Interactions of HMGB1/TLR2 and α-SMA/p62 were examined by immunoprecipitation and immunofluorescence. RESULTS: ISO-treated mice showed characteristic cardiac fibrosis, increased expression and co-localization of HMGB1 and TLR2, as well as impaired autophagic signals in myocardial tissues, which could be prevented by silencing TLR2. Exogenous administration of HMGB1 blocked the autophagic flux in fibroblasts, which caused extensive accumulation of collagen I and α-SMA. In addition, cardiac fibrosis was alleviated by GA treatment through abrogating the interaction between HMGB1 and TLR2. CONCLUSIONS: Our study suggests that the interaction between TLR2 and HMGB1 contributes to the pathogenesis of cardiac fibrosis via suppressing fibroblast autophagy, and that inhibiting HMGB1 with GA provides therapeutic benefits for the treatment of fibroproliferative heart diseases.

Toll-like receptor 4 knockout protects against isoproterenol-induced cardiac fibrosis: the role of autophagy.

BACKGROUND: Toll-like receptor 4 participates in the process of acute heart injury. The underlying mechanisms of its protection are multifactorial, but we hypothesized that toll-like receptor-mediated autophagy control plays a vital role. The purpose of this study was to clarify the effect of autophagy on cardiac fibrosis. METHODS: Cardiac fibrosis was induced by subcutaneous isoproterenol (ISO) injection, and rapamycin was simultaneously administered orally for 14 days. Animal echocardiography was then used to evaluate the success of the cardiac fibrosis model, and the mice were killed after the echocardiography examination. RESULTS: Toll-like receptor 4 knockout (TLR4 KO) mice had better heart function than did wild-type (WT) mice (P < .05). Rapamycin treatment reduced the left ventricular ejection fraction to 23.5% (P < .05), and the collagen volume fraction of the ISO and ISO plus rapamycin groups was 5.9% and 25.9%, respectively, in TLR4 KO mice. Compared with the WT mice, Beclin 1 and autophagy were downregulated in TLR4 KO mice (P < .05); however, the ISO plus rapamycin group had higher autophagy activity than did the ISO group in TLR4 KO mice (P < .05). CONCLUSIONS: Our results suggest that TLR4 KO-induced cardioprotection against ISO-induced cardiac fibrosis is associated with reduced autophagy induction. Cardiac fibroblast autophagy participates in its own activation. The moderate inhibition of autophagic activity may be a new strategy for treating cardiac fibrosis.