Angiotensin-Converting Enzyme Related-Polymorphisms on Inflammation, Muscle and Myocardial Damage After a Marathon Race

Abstract

Muscle damage is one of the most important factors that affect muscle fatigue during endurance exercise. Recent evidence suggests that the renin–angiotensin system impacts on skeletal muscle wasting. The aim of this study was to determine association between the AGT Met235Thr, ACE I/D and BDKRB2 −9/+9 polymorphisms with inflammation, myocardial and muscle injury induced by endurance exercise. Eighty-one Brazilian male runners participated in this study and completed the International Marathon of Sao Paulo. Muscle and myocardial damage markers (alanine transaminase, ALT, aspartate transaminase, AST, lactic dehydrogenase, LDH, creatine kinase, CK, Troponin, pro BNP, myoglobin, and CK-MB) and inflammatory mediators (IL-6, IL-8, IL-10, IL12p70, IL1β, and TNF-α) were determined one day before, immediately after, one day after, and three days after the event. Muscle damage was also determined fifteen days after race and angiotensinogen (AGT) Met235Thr, angiotensin-converting enzyme (ACE) I/D, and Bradykinin B2 receptor (BDKRB2) −9/+9 polymorphisms were determined. Marathon race participation induced an increase in all muscle damage and inflammatory markers evaluated (p < 0.0001). The muscle damage markers, troponin and pro BNP, CK and LDH and inflammatory markers, IL-6, IL-8, IL-1β and IL-10 were also higher in ACE II genotype immediately after race, compared to DD genotype. The percentage of runners higher responders (>500U/I) to CK levels was higher for II genotypes (69%) compared to DD and ID genotypes (38% and 40%, respectively) immediately after. Troponin, pro BNP and IL-1β, IL-8 levels were also elevated in AGT MM genotype compared to TT genotype athletes after and/or one day after race. BDKRB2 −9/−9 had pronounced response to LDH, CK, CK-MB and ALT and AST activities, myoglobin, troponin, IL-6, IL-8 levels immediately, one day and/or three days after race. The percentage of runners higher responders (>500U/I) to CK levels was greater for −9−9 and −9+9 genotypes (46 and 48%, respectively) compared to +9+9 genotypes (31%) immediately after. ACE II, AGT MM, and BDKRB2 −9−9 genotypes may increase the susceptibility to inflammation, muscle injury after endurance exercise and could be used to predict the development of clinical conditions associated with muscle damage and myocardial injury.

Dynamics of Specific cfDNA Fragments in the Plasma of Full Marathon Participants

“…MG is known to leak into the blood immediately after muscle damage, and WBCs reflect an acute inflammatory response. Previous reports have also shown that WBC and MG levels in the blood are significantly increased immediately after running a marathon race [ 19 , 20 , 21 ]. In addition, strong correlations were confirmed in our current study between spcfDNA-1 and WBC or MG ( Figure 5 a,b).…”

Characterizing Marathon-Induced Metabolic Changes Using 1H-NMR Metabolomics

“…Some of these immunological effects include acute pro-and anti-inflammatory responses [6], damage to bronchial epithelial cells [7], a perturbed mucosal immune system, and higher susceptibility to symptoms of upper respiratory tract infections [8]. On a physiological level, short-term occurrences of muscle damage [9] and medial tibial stress syndrome [10] are common for the average marathon participant, while more acute effects such as an increased risk for myocardial fibrosis [11], deleterious cardiac structural changes [12], as well as acute liver and renal damage [13] have been reported for extreme/elite veteran marathon athletes.…”

Urine proteomics as a non-invasive approach to monitor exertional rhabdomyolysis during military training

“…Elucidation of the mechanisms involved in muscle damage and inflammation during strenuous physical exercise is important to predict clinical complications. Recently, it has been reported that polymorphisms of the angiotensin-converting related enzyme impact on inflammation muscle and myocardial damage during endurance exercise (Sierra et al, 2019). We show herein the association of polymorphisms of the angiotensin-converting enzyme (ACE) I/D and angiotensinogen (AGT) Met235Thr with the urinary proteome after strenuous physical exercise.…”

“…The polymorphisms of the angiotensin-converting enzyme (ACE) I/D gene showed an increase in the abundance of proteins related to oxidative stress (HBB, PRDX6, CALM3, PPIA and FABP4) compared to the ACE II genotype, being the latter correlated with higher risk to develop muscle damage (Yamin et al, 2007). The ACE DD and AGT TT genotypes were associated with low muscle damage and indicate that the renin-angiotensin-aldosterone system (RAS) plays an important role in exercise-induced muscle damage (Sierra et al, 2019). The RAS is responsible for regulating important processes, which include blood pressure control, water, electrolyte balance and recent evidence suggests impacts on skeletal muscle wasting (Dai et al, 2019).…”