Extreme exercise enhances chromogranin A levels correlating with stress levels but not with cardiac burden.

OBJECTIVE: Stress and heart failure are associated with increased systemic levels of chromogranin A (CGA). Here we analyzed the effects of marathon running on systemic CGA levels and the association with cardiac burden and stress. METHODS: We recruited 47 lean and obese runners for a 10week training program aiming at running a marathon. Heart rates, individual fitness and marathon finishing times were monitored. CGA, proBNP and troponin T levels were analyzed by ELISA. RESULTS: We found a significant increase of CGA (+51%; p<0.01) in lean runners after marathon. The obese group showed the highest troponin T (0.22ng/ml; p<0.01) and proBNP (176.6ng/ml; p<0.01) levels. There were no correlations between proBNP, troponin T and CGA. An inverse correlation (r=-0.45; p<0.01) was found between CGA and finishing times. CONCLUSION: Marathon running is associated with increased CGA levels. However, this does not seem to reflect cardiac burden but rather marathon induced stress.

Modulation of dendritic cells and toll-like receptors by marathon running.

The focus of this study was to assess exercise-induced alterations of circulating dendritic cell (DC) subpopulations and toll-like receptor (TLR) expression after marathon running. Blood sampling was performed in 15 obese non-elite (ONE), 16 lean non-elite (LNE) and 16 lean elite (LE) marathon runners pre- and post-marathon as well as 24 h after the race. Circulating DC-fractions were measured by flow-cytometry analyzing myeloid DCs (BDCA-1+) and plasmacytoid DCs (BDCA-2+). We further analyzed the (TLR) -2/-4/-7 in peripheral blood mononuclear cells (rt-PCR/Western Blot) and the cytokines CRP, IL-6, IL-10, TNF-α and oxLDL by ELISA. After the marathon, BDCA-1 increased significantly in all groups [LE (pre/post): 0.35/0.47%; LNE: 0.26/0.50% and ONE: 0.30/0.49%; all p < 0.05]. In contrast, we found a significant decrease for BDCA-2 directly after the marathon (LE: 0.09/0.01%; LNE: 0.12/0.03% and ONE: 0.10/0.02%; all p < 0.05). Levels of TLR-7 mRNA decreased in all groups post-marathon (LE 44%, LNE 67% and ONE 52%; all p < 0.01), with a consecutive protein reduction (LE 31%, LNE 52%, ONE 42%; all p < 0.05) 24 h later. IL-6 and IL-10 levels increased immediately after the run, whereas increases of TNF-α and CRP-levels were seen after 24 h. oxLDL levels remained unchanged post-marathon. In our study population, we did not find any relevant differences regarding training level or body weight. Prolonged endurance exercise induces both pro- and anti-inflammatory cytokines. Anti-inflammatory cytokines, such as IL-10, may help to prevent excessive oxidative stress. Marathon running is associated with alterations of DC subsets and TLR-expression independent of training level or body weight. Myeloid and plasmacytoid DCs are differently affected by the excessive physical stress. Immunomodulatory mechanisms seem to play a key role in the response and adaptation to acute excessive exercise.

Exercise-induced alterations of retinal vessel diameters and cardiovascular risk reduction in obesity.

BACKGROUND: The retinal microcirculation is affected early in the process of atherosclerosis and retinal vessel caliber is an emerging cardiovascular risk factor. Obesity is associated with vascular dysfunction. Here, we investigate the effect of regular exercise on retinal vessel diameters in lean and obese runners. We analyze a possible link to alterations of the nitric oxide (NO)-asymmetric dimethylarginine (ADMA) pathway. METHODS: Retinal vessel diameters were assessed by means of a static vessel analyzer (SVA-T) in 15 obese athletes (OA), 14 lean amateur athletes (AA) and 17 lean elite athletes (EA) following a 10 week training program. ADMA serum levels were detected by ELISA and dimethylarginine dimethylaminohydrolase (DDAH) -1/-2 mRNA-expression in peripheral mononuclear cells (PBMC) was analyzed by real time PCR. RESULTS: At baseline, the mean (±SD) arteriolar to venular diameter ratio (AVR) was impaired in obese (OA: 0.81±0.05) compared to lean subjects (AA: 0.87±0.07; EA: 0.94±0.05). The individual fitness levels correlated with AVR (rho=+0.66; P<0.001) and the training program improved AVR in all groups (P<0.001), normalising AVR in the obese (OA: 0.86±0.1). A training-induced arteriolar dilatation was found in OA (P=0.01), which was accompanied by a significant decrease of ADMA levels (0.56±0.12-0.46±0.12 µmoll(-1); P<0.028). DDAH-1 mRNA levels in PBMC increased in all groups (P<0.01). CONCLUSIONS: Cardiovascular fitness and body composition affect retinal vessel diameters. Regular exercise reverses the subclinical impairment of the retinal microvasculature in obesity by inducing retinal arteriolar dilatation. The NO/ADMA pathway may play a key role in the training-induced improvement of microvascular function, which has the potential to counteract progression of small vessel disease.