ECSS Paris 2023: CP-PN15
INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) regulates the renin-angiotensin system (RAS) by converting angiotensin II into angiotensin (1-7), with vasodilatory, antioxidative, and anti-inflammatory effects. In skeletal muscle, ACE2 is necessary for adaptation to exercise. TMPRSS2 cleaves ACE2, affecting shedding, and viral entry in SARS-CoV-2 infection, being involved in muscle post-viral disorders, oxidative stress (OS), and inflammation. Animal models suggest exercise benefits RAS balance, but human data are lacking. Given the role of OS in ACE2 and TMPRSS2 regulation, we investigated whether Sprint Interval Training (SIT) either alone or combined with post-exercise ischaemia—an intervention transiently elevating OS upon reperfusion—drives molecular adaptations in RAS components in human skeletal muscle. We hypothesised that brief ischaemia during SIT recovery would boost ACE2 and TMPRSS2 expression levels through OS-related mechanisms. METHODS: Ten volunteers (7M/3W) completed a SIT program (4-6 × 30s sprints, 4min rest) in six sessions over two weeks. After each sprint, occlusion (300mmHg, 30-50s) was applied to one leg, followed by rest. PRE and POST training, participants did an incremental exercise to exhaustion (IE), a 90min rest, and six supramaximal exercise bouts (SPE, 120%VO₂max) with 20s bilateral ischaemia applied between bouts. V. lateralis biopsies were taken at baseline (BS), 90min post-IE, and immediately post-SPE unilaterally at PRE and bilaterally at POST (SIT-IS vs. SIT-CT leg) for WB analysis. Stats: ANOVA, t-test, Pearson’s correlation. RESULTS: Basal ACE2 and TMPRSS2 increased by ~145% with SIT-IS but did not change with SIT-CT (p<.05). Basal ACE1 rose by 66% with SIT-IS and dropped 24% with SIT-CT (p<.001). AT2R levels decreased by 19% with SIT-IS (all timepoints). Acute high-intensity exercise increased ACE2 (61%) and TMPRSS2 (88%) after IE, but not further with SPE (p>.05 vs. BS). SIT-IS blunted these effects, unlike SIT-CT (p<.05). ACE1 increased acutely only after SIT-CT (53%) and similarly after IE and SPE (p<.05), with no AT2R changes. ACE2 and TMPRSS2 correlated across conditions (R=.74) and with pS359 p47 NOX2 (R= .59/.72), Nrf2/Keap1 (R=.74/.73), and Catalase (R=.73/.57), all p<.001. ACE1 correlated with ACE2 (R=.39, p<.001) and TMPRSS2 (R=.21, p=.04). AT2R negatively correlated with ACE2 (R=-.28, p=.008). CONCLUSION: While SIT alone did not upregulate ACE2 or TMPRSS2 in skeletal muscle, SIT combined with post-exercise ischaemia-reperfusion potentiated their expression, likely via an OS-related mechanism, as indicated by Nrf2/Keap1 activation. The blunted post-exercise increases in ACE2 and TMPRSS2 after training with post-exercise ischaemia suggest increased antioxidant capacity after training with ischaemia. The associations between ACE2, TMPRSS2, and OS signalling support this interpretation. PID2021-125354OB-C21/AEI/10.13039/501100011033/FEDER, EU; CSD (EXP_75097); SD-24/03 CUCIC. AGS: Catalina Ruiz postdoctoral grant (CUCIC-GOBCAN and ESF).
Read CV GIOVANNI GARCIAECSS Paris 2023: CP-PN15
INTRODUCTION: A frequent genetic variant in the alpha actinin-3 gene (ACTN-3, c.1729C>T (rs1815739)) has been linked to the progression of soccer career [2], the prevalence and severity of muscle injuries [3], and elite athletic performance [1]. While the TT genotype appears to have a detrimental impact on football career advancement and the likelihood of developing muscle injuries, the C allele and the CC genotype of the ACTN-3 polymorphism appear to favour the capacity to produce strong and forceful muscle contractions, which are necessary during sprinting performance. A crucial component of contemporary football is high-intensity running, which can distinguish between players at the highest level of competition and those at a lower level [4]. We hypothesized that football players harbouring the C allele would have a higher maximal running speed (MRS) during matches than those footballers with the TT genotype. METHODS: MRS was collected, using a Global Position System (GPS) at high sampling frequencies (50 Hz), from 45 elite football players of a same professional football team during 26 official matches for a total of 707 matches observations. Genomic DNA was extracted using a buccal swab, and the ACTN-3 genotype was performed using a RFLP PCR method. RESULTS: The main finding was that CC players showed significantly higher MRS than TT players (CC=33.1±1.3 km•h-1 vs TT=31.5±1.9 km•h-1, p=0.041). Moreover, the players harbouring a copy of the C allele showed a trend toward higher MRS than players carriers of the TT genotype (CC+CT= 32.9±1.5 km•h-1 vs TT=31.5±1.9 km•h-1, p=0.06). The MRS (36.4 km•h-1) was registered for a player carrier of CC genotype, while the lower running speed (29.8 km•h-1) was reordered for a player carrier of TT genotype. CONCLUSION: For the first time, we discovered an association between elite football players match-play maximal sprinting speed and the ACTN-3 polymorphism. If our findings will be confirmed in more extensive studies, they may be applied in the future to modify training regimens in order to improve football performance. References 1. Yang et al. Am J Hum Genet. 2003, 73:627-31. 2. Coelho et al. Int J Sports Med. 2018, 39(14):1088-93. 3. Massidda et al. Clin J Sport Med. 2019, 29(1):57-61. 4. Carling et al. J Sport Sci. (2012) 30(4):325–36.
Read CV MYOSOTIS MASSIDDAECSS Paris 2023: CP-PN15
INTRODUCTION: The associations between the AGTR2 genotypes and athletic performance have been proven in various sports disciplines. However, there is a lack of studies investigating the AGTR2 rs11091046 polymorphism in sport climbers. This study aimed to examine whether the rs11091046 polymorphism in the AGTR2 gene is associated with athletic climbing status in sport climbers from Poland. METHODS: AGTR2 genotypes of 142 sport climbers (55 female, 87 male athletes) were compared with 89 sedentary controls. Genotyping was performed using TaqMan SNP genotyping assays on Thermo Fisher Scientific (Waltham, MA, USA). Deviation of genotype frequencies in sport climbers and controls from Hardy-Weinberg equilibrium (HWE) was assessed using a Chi-squared test with Yates’s correction. For a 95% confidence interval (CI), we assumed p=0.05 and χ2=3.84; therefore, if the χ2≤3.84 and the corresponding p≥0.05, the population is in HWE. Both male and female athletes were classified into four groups: “Higher elite”, “Elite”, “Advanced”, and “Intermediate” based on the self-reported most difficult route ever climbed converted to the International Rock Climbing Research Association (IRCRA) Reporting Scale (IRS) based on IRCRA standards for the International Rock Climbing Association. RESULTS: Mean IRCRA scores were 19.48 (SD = 3.92) for individuals with the AA genotype, 19.66 (SD = 3.58) for AC, and 17.07 (SD = 3.41) for CC. The chi-square test showed a significant relationship between the AGTR2 genotype and the IRCRA level in the group of male sport climbers (Χ² = 14.85, df = 6, p = 0.02) in comparison to female climbers (p=0.96). Most male climbers with AA and AC genotypes were in the "Advanced" category, while in the CC group, most athletes were in the "Intermediate" category. Notably, no results were recorded among athletes with the CC genotype in the "Elite" and "Higher Elite" categories. CONCLUSION: The results suggest that the impact of the AGTR2 (rs11091046) polymorphism on IRCRA results may be gender dependent. The male sport climbers with the CC genotype obtain lower IRCRA scores than athletes with the AC genotype, which may indicate the potential impact of this polymorphism on the climbing status. The AGTR2 gene is located on the X chromosome, which may explain the difference in results - in men, the effect of a single allele may be more pronounced than in women, in whom a second copy of the gene may compensate for the possible negative impact of the risk allele. Future studies should include a larger sample size of women to determine further whether the effect of this polymorphism on the IRCRA score is indeed specific to men.
Read CV Agata GinsztECSS Paris 2023: CP-PN15