Discussion
peripheral arterial disease, arteriogenesis, PAD, diabetes mellitus, heart failure, atherosclerosis
CELIAC DISEASE, PERIPHERAL ARTERIAL DISEASE, DIABETES MELLITUS, HYPOXIC, NEOVASCULARISATION, PAD, HEART FAILURE, PERIPHERAL ARTERIAL DISEASE, ATHEROSCLEROSIS, CORONARY ARTERY DISEASE
We investigated the concentration of eight circulating miRNAs in patients with peripheral arterial disease in the lower extremities before and after a vigorous- and a moderate-intensity bout of walking exercise. In the vigorous-intensity intervention, a higher anaerobic metabolic response but no significant intervention effect on miRNA expression occurred. Although lactate response was lower, the moderate-intensity intervention led to an upregulation of two miRNA concentrations. Exercise intensity and consecutive metabolic response, indicated by lactate, showed no significant association to miRNA expression. Hypothesis 1, that vigorous-intensity training leads to a higher metabolic response than moderate-intensity training, is thus only partially verified. Hypothesis 2, that moderate-intensity training leads to a different profile of circulating miRNAs compared to high intensity training, is verified.The moderate-intensity walking training led to lower lactate and maximal heart rate values compared to the vigorous-intensity walking training. The vigorous-intensity intervention was terminated after reaching subjective exertion one time and the distances covered on the treadmill ranged from 671 to 1213 m and thus was shorter than the distance covered in the moderate-intensity walking intervention. The variance in the covered distance until exhaustion underlines the different manifestations of peripheral arterial disease-related impairments, that may result in different metabolic responses during exercise. When comparing the heart rate during interventions to the calculated maximal heart rate, the participants averagely reached 56% of their individual maximal heart rate after the moderate walking training, with a spread of the difference from 48 to 64%. In contrast, after the vigorous-intensity training, the participants had a significantly higher percentage heart rate with a mean value of 78% of HRmax (min: 63%, max: 95%). According to the relative intensity table (Bjarnason-Wehrens et al. In conservative therapy, the effect of exercise on arteriogenesis is considered as an important mechanism. Physical training is thought to have the potential to stimulate neovascularisation in hypoxic and ischaemic tissues, such as the myocardium or peripheral limbs (Guerreiro et al. The regulation of miRNAs appears to be complex and is certainly not fully understood (Gulyaeva and Kushlinskiy The individual miRNAs are associated with different metabolic reactions, different parts of the human organism and different signalling pathways. MiRNA-142-5p is, among others, associated, with the pathways of VEGF and mTOR signalling, especially in cardiac muscles. This miRNA could be a factor for improvements of the vascular system and arteriogenesis. Moreover, the upregulation of miR‑142‑5p expression is related with the apoptosis in human macrophages by targeting TGF‑β2, this effect could play an important role in the progression of atherosclerosis (Xu et al. MiRNA-424-5p is associated with the expression of selected endothelial angiogenetic mediators in response to these growth factors (VEGF and bFGF) and is, therefore, considered as a “hypoximiR” (Chamorro-Jorganes et al. A study limitation is the small number of subjects as a result to the corona pandemic. Individuals with PAD tend to have many comorbidities that may be related to the observed outcomes. Some comorbidities affect similar cardiovascular and metabolic mechanisms as PAD. Examples include diabetes mellitus, coronary artery disease, heart failure, arterial hypertension and celiac disease.Our results are consistent with the proposed epigenetic potential of activity interventions that may alter miRNA expression. Since each miRNA is predicted to have many targets, we did not identify any direct association with other measures. Therefore, we postulate that further studies are necessary to adjust the intensity and extent of training to gain more information about the relationship between individual miRNAs, Peripheral arterial disease and human metabolism. This could be an added value (1) in training control and (2) in diagnostic screening of miRNAs to stratify responders and non-responders for individualization of treatment in PAD patients.