Characteristics of athletes and non-athlete individuals.

<p>* <i>p</i><0.01 versus all non-athletes,</p><p>^†<i>p</i><0.01 versus men non-athletes,</p><p>^‡<i>p</i><0.01 versus women non-athletes.</p><p>Body mass index was different between athletes and non-athletes and between men and women (<i>p</i><0.05). Height, weight, body surface area and body mass index was different between men and women individuals in the athlete and non-athlete groups (<i>p</i><0.05). Age was not different between study groups.</p><p>Characteristics of athletes and non-athlete individuals.</p

Characteristics of different genotypes within athletes and non-athletes (irrespective of their gender).

<p>n—number of individuals; LVEF—left ventricular ejection fraction; LVEDVi—left ventricular end-diastolic volume index; LVESVi—left ventricular end-systolic ventricular index; LVMi—left ventricular mass index; LVSVi—left ventricular stroke volume index; RVEF—right ventricular ejection fraction; RVEDVi—right ventricular end-diastolic volume index; RVESVi—right ventricular end-systolic volume index; RVSVi—right ventricular stroke volume index; RVMi—right ventricular mass index</p><p>Analysis of variance showed significant differences among the inspected groups: athletes and non-athletes with and without the Aspartate allele. Post hoc tests revealed a significant influence of the genotype on resting RVSVi and RVMi in athletes,</p><p>^# p<0.001 vs Asp carriers within the athlete group.</p><p>Athletic status had significant influence on all parameters with the exception of LVEF and RVEF,</p><p>* p<0.001 vs non-athletes irrespective of genotype.</p><p>Characteristics of different genotypes within athletes and non-athletes (irrespective of their gender).</p

Nitric oxide synthase 3 gene 298 Glu/Asp genotype distribution in athletes and in non-athlete controls.

<p>Number of individuals with different genotypes in the different groups. Percentage in brackets represents the allelic frequency within the subgroup.</p><p>Nitric oxide synthase 3 gene 298 Glu/Asp genotype distribution in athletes and in non-athlete controls.</p

Characteristics of athlete and non-athlete men and women.

<p>n—number of individuals; LVEF—left ventricular ejection fraction; LVEDVi—left ventricular end-diastolic volume index; LVESVi—left ventricular end-systolic ventricular index; LVMi—left ventricular mass index; LVSVi—left ventricular stroke volume index; RVEF—right ventricular ejection fraction; RVEDVi—right ventricular end-diastolic volume index; RVESVi—right ventricular end-systolic volume index; RVSVi—right ventricular stroke volume index; RVMi—right ventricular mass index.</p><p>* <i>p</i><0.01 versus all non-athletes,</p><p>^‡<i>p</i><0.01 versus women.</p><p>Age was not different between study groups.</p><p>Characteristics of athlete and non-athlete men and women.</p

Characteristics of male and female athletes and athletes with, or without the Asp allele.

<p>In this age matched population of elite athletes with a similar social and ethnic background linear regression analysis revealed that both male gender and the presence of the Asp allele are independent predictors for higher resting right ventricular stroke volume index (RVSVi) and right ventricular mass index (RVMi) values.</p><p>^‡ p<0.001 vs women,</p><p>^# p<0.001 vs Aspartate carriers.</p><p>Characteristics of male and female athletes and athletes with, or without the Asp allele.</p

Effect of pharmacological inhibition of RIP2 and NOD1 siRNA mediated knockdown on responses of hESC-EC to <i>Haemophilus influenzae</i> (HIN) and C12-iE-DAP.

<p>(A) Relative expression (vs. GAPDH) of NOD1 following 48 hour incubation with NOD1 siRNA normalized to non-targeting siRNA; n = 6. (B) CXCL8 release from hESC-EC following 48 hour pre-incubation with non-targeting siRNA (open bars) or NOD1-siRNA (filled bars) and 24 hour treatment +/− C12-iE-DAP (10 µg/ml) or <i>Haemophilus influenzae (HIN)</i> (10⁷–10⁸ CFU/ml); n = 7–8. (C) Effect of GSK'214 (300 nM; RIP2 inhibitor) or GSK'217 (300 nM; NOD1 inhibitor), given 30 minutes before a 24 hour treatment with HIN (10⁷ CFU/ml) or C12-iE-DAP (10 µg/ml) on CXCL8 release; n = 4. It should be noted that GSK drugs increased CXCL8 release under basal conditions; for each experiment this was subtracted from treatment groups. For panel A, statistical significance was determined by one-sample t-test. For panel B statistical significance within siRNA groups was determined by one-way ANOVA followed by Dunnett's multiple comparison test (*p<0.05), and between groups by two-way ANOVA followed by Bonferroni's post-test (+p<0.05). For panel C statistical significance for the effects of inhibitor of C12-iE-DAP or HIN induced CXCL8 was determined by one-way ANOVA followed by Dunnett's multiple comparison test (*p<0.05).</p

MSD analysis of cytokine (pg/ml) release from hESC-EC.

<p>Data mean are ± SEM for n = 3. hESC-EC were treated for 24 hours with vehicle, LPS (1 µg/ml), or C12-iE-DAP (10 µg/ml). Statistical significance was determined by one-way ANOVA followed by Dunnett's multiple comparison test (*p<0.05). ND = non-detectable.</p

Responses of hESC-EC and HUVEC to 24 hour infection with <i>Heamophilus influenzae.</i>

<p>(A) Effect of LPS (1 µg/ml) or C12-iE-DAP (10 µg/ml) on CXCL8 release from hESC-EC and HUVEC after 24 hours. (B) Effect of <i>Haemophilus influenzae</i> (HIN) (10⁵–10⁸ CFU/ml) on CXCL8 release from hESC-EC (solid line) or HUVEC (dashed line) after 24 hours. Data are mean ± SEM; n = 3 representative of 6 hESC-EC isolations. Statistical significance for responses to drugs or bacteria was determined by one-way ANOVA followed by Dunnett's multiple comparison test (p<0.05).</p

MSD analysis of cytokine (pg/ml) release from HUVEC.

<p>Data are mean ± SEM for n = 3. HUVEC were treated for 24 hours with vehicle, LPS (1 µg/ml), or C12-iE-DAP (10 µg/ml). Statistical significance was determined by one-way ANOVA followed by Dunnett's multiple comparison test (*p<0.05).</p

Effect of <i>in vivo</i> ‘conditioning’ on TLR4 and NOD1 expression.

<p>TLR4 and NOD1 expression in (A) hESC-EC and (B) HUVEC before (pre-implant; open bars) and 21 days after (post-implant; filled bars) implantation <i>in vivo</i> (‘conditioning’). Data are mean ± SEM and are normalized at unity (1) to gene levels in pre-implant cells. HUVEC; NOD1 pre-implant n = 8, post implant n = 4: HUVEC; TLR4 pre-implant n = 10, post implant n = 3. hESC-ECs; NOD1 pre-implant n = 6, post implant n = 5: hESC-ECs; TLR4 pre-implant n = 10, post implant n = 6. Data was obtained from 2 independent experiments (using up to 12 rats per group). Statistical significance was determined by one-sample t-test where results were compared to a theoretical control of 1 (*p<0.05). ND = none detectable.</p