Exercise-Induced Vascular Adaptations under Artificially Versus Pathologically Reduced Blood Flow: A Focus Review with Special Emphasis on Arteriogenesis

Abstract

Background: The vascular effects of training under blood flow restriction (BFR) in healthy persons can serve as a model for the exercise mechanism in lower extremity arterial disease (LEAD) patients. Both mechanisms are, inter alia, characterized by lower blood flow in the lower limbs. We aimed to describe and compare the underlying mechanism of exercise-induced effects of disease- and external application-BFR methods. Methods: We completed a narrative focus review after systematic literature research. We included only studies on healthy participants or those with LEAD. Both male and female adults were considered eligible. The target intervention was exercise with a reduced blood flow due to disease or external application. Results: We identified 416 publications. After the application of inclusion and exclusion criteria, 39 manuscripts were included in the vascular adaption part. Major mechanisms involving exercise-mediated benefits in treating LEAD included: inflammatory processes suppression, proinflammatory immune cells, improvement of endothelial function, remodeling of skeletal muscle, and additional vascularization (arteriogenesis). Mechanisms resulting from external BFR application included: increased release of anabolic growth factors, stimulated muscle protein synthesis, higher concentrations of heat shock proteins and nitric oxide synthase, lower levels in myostatin, and stimulation of S6K1. Conclusions: A main difference between the two comparators is the venous blood return, which is restricted in BFR but not in LEAD. Major similarities include the overall ischemic situation, the changes in microRNA (miRNA) expression, and the increased production of NOS with their associated arteriogenesis after training with BFR.

Molecular Mechanisms Associated with ROS-Dependent Angiogenesis in Lower Extremity Artery Disease

“…It is important to note that compromised arterial inflow results in angiogenesis due to distal tissue ischemia and arteriogenesis that occurs close to the site of arterial trunk occlusion [ 32 ]. Structural and functional adaptations of the vasculature can also be induced by exercise training in humans [ 33 ]. LEAD symptoms may be the result of not only an obstructive vascular process but also an impaired neovascularization response [ 1 ].…”

“…Collateral circulation occurs between arterioles in most healthy tissues and in pathological conditions like ischemic injury [ 39 ]. Arteriogenesis can be induced by regular exercise or muscle loading in humans in physiological conditions [ 33 , 49 , 69 ]. A more regular exercise regimen was also proposed to be required for sufficient arteriogenesis to compensate for an arterial occlusion in LEAD [ 49 ].…”

“…It explains why significant stenosis/occlusion of main arteries may remain asymptomatic in patients with chronic LEAD for many years. Exercise therapy can influence the vascular system supply to the ischemic limb by promoting both angiogenesis and arteriogenesis [ 33 ]. An increase of angiogenic and arteriogenic factors, such as VEGF and HIF-1 alpha, was observed after regular exercise [ 70 ].…”

Arteriogenesis and Therapeutic Angiogenesis in Its Multiple Aspects

“…In their paper, Vogel et al describe exercise-induced vascular adaptations under pathologically reduced blood flow and compare this to changes after artificially reduced blood flow. Major similarities include the overall ischemic situation, the changes in microRNA (miRNA) expression, and the increased production of nitric oxide synthase (NOS) with their associated arteriogenesis after training with blood flow restriction [11].…”

Intradialytic exercise with blood flow restriction is more effective than conventional exercise in improving walking endurance in hemodialysis patients: Response to comments on a randomized control trial

“…The review authors claim future clinical trials applying blood flow restriction training in peripheral arterial disease patients. 7…”