Physical Exercise Promotes DNase Activity Enhancing the Capacity to Degrade Neutrophil Extracellular Traps

Abstract

(1) Background: An unhealthy lifestyle is a significant contributor to the development of chronic diseases. Physical activity can benefit primary and secondary prevention. Higher DNase activity is associated with favourable outcomes after cardiovascular (CV) events. In this study, we aimed to investigate the influence of consequent endurance exercise on DNase activity. (2) Methods: 98 subjects with at least one CV risk factor but the physical ability to perform endurance training were included. Individuals performed a bicycle stress test at the beginning and after 8 months to assess physical performance. In between, all participants were instructed to engage in guideline-directed physical activity. Blood samples were drawn in two-month intervals to assess routine laboratory parameters, cell-free DNA (cfDNA), and DNase activity. (3) Results: Prevailing CV risk factors were overweight (65.9%), a positive family history (44.9%), hypertension (32.7%) and smoking (20.4%). Performance changed by 7.8 ± 9.1% after 8 months. Comparison of baseline to 8 months revealed a decrease in cfDNA and an increase in DNase activity. This effect was driven by participants who achieved a performance gain. (4) Conclusions: Regular physical activity might improve CV health by increasing DNase activity and thereby, the capacity to lower pro-inflammatory signalling, complementing measures of primary and secondary prevention.

Effect of a 12-Week Walking Program Monitored by Global Physical Capacity Score (GPCS) on Circulating Cell-Free mtDNA and DNase Activity in Patients with Irritable Bowel Syndrome

“…Regarding cf-mtDNA, the results of the present study confirmed the high natural interindividual variation in the concentration of this molecule [36], without differences in this feature between the IBS patients and non-IBS subjects (Figure 3). Furthermore, as shown in Figure 4A, in accordance with data already reported by others [30,31,37], the results showed a reduction in cf-mtDNA in the non-IBS group, although not significant, as the adaptive response to prolonged exercise. Interestingly, the lowering of cf-mtDNA appeared to be associated with greater benefits in PC, as shown by the significantly higher GPCS values reached by subjects who experienced the reduction in circulating cf-mtDNA compared to those who experienced the gain.…”

“…cf-DNA changes have already been described in association with chronic exercise [37]. Some studies found a decline in cf-mtDNA in response to prolonged exercise [31], associated with increased DNase activity [30]. The health benefits of exercise may depend on the ability of muscles to interact with the inflammatory cells and stimulate or resolve inflammation to maintain immune homeostasis [38].…”

“…Total DNase activity in the serum samples was assessed using a single radial enzyme diffusion assay [30]. A brief overview of the procedure is as follows: (1) Calf thymus DNA (Sigma-Aldrich, St. Louis, MO, USA) was dissolved at a concentration of 100 µg/mL in assay buffer, which included 2.5 X GelRed (Sigma-Aldrich, St. Louis, MO, USA) as a DNA-binding fluorescent dye.…”

“…Indeed, cf-DNA is quantitatively released into the plasma in the non-pathological setting of acute and intense physical exercise, thus activat-ing the innate immune response [29]. However, several reports have provided evidence that regular PA, in turn, promotes the removal of cf-DNA, thereby lowering pro-inflammatory signaling [30,31].…”

Impact of Impaired Cholesterol Homeostasis on Neutrophils in Atherosclerosis

“…19 Inhibition of NET formation by DNase (deoxyribonuclease 1) treatment attenuates local inflammation and promotes plaque regression. 20 Recent studies have demonstrated that NET clearance can be regulated by either increasing or decreasing circulating DNase activity via exercise 21 or hypercholesterolemia, 22 respectively. Additionally, neutrophils secrete matrix metalloproteinases that degrade the extracellular matrix and progressively reduce the structural integrity of plaques, especially in rupture-prone shoulder regions.…”