Blood flow restriction exercise stimulates mobilization of hematopoietic stem/progenitor cells and increases the circulating ACE2 levels in healthy adults

Joshi, Shrinidh; Mahoney, Sean; Jahan, Jesmin; Pitts, Logan; Hackney, Kyle J.; Jarajapu, Yagna

doi:10.1152/japplphysiol.00109.2020

Cited by 19 publications

(20 citation statements)

References 44 publications

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“…Shedding of ACE2 in airway epithelial cells occurs constitutively but is also inducible (6, 14, 16, 40). Different stimuli increase ACE2 shedding, including cytokines and hypoxia (6, 16, 41, 42). Ang II also increases ACE2 shedding (43) and potentially high levels of Ang II in infected tissues can cause shedding of ACE2 which may reach the circulation due to increased vascular permeability.…”

Section: Discussionmentioning

confidence: 99%

Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers

Lundström

Ziegler

Havervall

et al. 2021

Preprint

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Rationale: Angiotensin-converting enzyme 2 (ACE2) is the main entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how SARS-CoV-2 interactions with ACE2 influences the renin-angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) is unknown. Objective: To measure circulating ACE2 and ACE levels in COVID-19 patients and investigate associations with risk factors, outcome and inflammatory markers. Methods and results: Soluble ACE2 (sACE2) and sACE concentrations were measured by ELISA in plasma samples from 114 hospital-treated COVID-19 patients and 10 healthy controls. Follow-up samples after four months were available for 58/114 patients. Von Willebrand factor (VWF), factor VIII (fVIII), D-dimer, interleukin 6 (IL-6), tumor necrosis factor α and plasminogen activator inhibitor 1 (PAI-1) had previously been determined. Levels of sACE2 were higher in COVID-19 patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < 0.0001. sACE2 was higher in men than women, but were not affected by other risk factors for severe COVID-19. sACE2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < 0.0001, but remained higher than in healthy controls, p=0.012. Follow-up sACE2 levels were higher with increasing age, BMI, total number of comorbidities, for patients with diabetes and patients on RAS-inhibition. sACE was marginally lower during COVID-19 compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. Levels of sACE2 and sACE did not differ depending on survival or disease severity (care level, respiratory support). sACE2 during COVID-19 correlated with VWF, fVIII and D-dimer, while sACE correlated with IL-6, TNFα and PAI-1. Conclusions: sACE2 was transiently elevated in COVID-19, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 differed distinctly in their correlations with markers of inflammation and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.

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Section: Discussionmentioning

confidence: 99%

Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers

Lundström

Ziegler

Havervall

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…These findings were supported by increased mRNA expression of vascular endothelial growth factor (VEGF), VEGF receptor 2, hypoxia-inducible factor 1α (HIF-1α), and endothelial nitric oxide synthase (eNOS) after BFRT [42]. Moreover, compared with passive sitting as the control condition, four sets of unilateral BFRT resulted in higher levels of angiotensin-converting enzyme 2 and an increased number of vasculogenic progenitor cells, which underlies the vascular regeneration effect of BFRT on skeletal muscle [43].…”

Section: Vascular Adaptationsmentioning

confidence: 99%

Effects of Blood Flow Restriction Exercise and Possible Applications in Type 2 Diabetes

Saatmann

Zaharia

Loenneke

et al. 2021

Trends in Endocrinology & Metabolism

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Blood flow restriction resistance training (BFRT) employs partial vascular occlusion of exercising muscles via inflation cuffs. Compared with high-load resistance training, mechanical load is markedly reduced with BFRT, but induces similar gains in muscle mass and strength. BFRT is thus an effective training strategy for people with physical limitations. Recent research indicates that BFRT has beneficial effects on glucose and mitochondrial metabolism. BFRT may therefore qualify as a valuable exercise alternative for individuals with type 2 diabetes (T2D), a disorder characterized by impaired glucose metabolism, musculoskeletal decline, and exacerbated progression of sarcopenia. This review covers the effects of BFRT in healthy populations and in persons with impaired physical fitness, the mechanisms of action of this novel training modality, and possible applications for individuals with T2D. Blood Flow Restriction Training as an Alternative for Maintaining Physical Performance and Health? Endurance training typically improves cardiorespiratory fitness [1] which is associated with lower mortality from any cause as well as reduced cardiovascular disease risk [2]. In addition, individuals with higher muscle mass and strength are at lower risk of death [3]. Classical resistance training (RT) effectively improves skeletal muscle mass and strength as well as glycemic control [4,5]. In that sense, exercise training holds great promise for the prevention and management of metabolic diseases such as type 2 diabetes (T2D) (Box 1). However, to achieve health benefits from RT, loads equating to 70% or more of the individual one-repetition maximum (1-RM; see Glossary) are often recommended [6]. High muscle-tendon loads may not be suitable for people with physical limitations or clinical populations who are affected by muscle wasting and reduced muscle strength. Effective alternative countermeasures are therefore urgently needed for these individuals to avoid frailty. One promising exercise modality is blood flow restriction training (BFRT) (Box 2). It has been shown that blood flow restriction (BFR) alone, even without concomitant exercise training, can be effective in mitigating the reductions in muscle strength and atrophy that result from immobilization [7]. Interestingly, BFR without exercise prevented reductions of muscle strength and leg circumference in cast-immobilized patients [8] as well as declines of muscular weakness induced by chronic unloading [9]. Along these lines, previous studies showed that BFR without exercise diminishes both postoperative muscle atrophy [10] and bed-rest-related muscle atrophy [11]. This training modality typically utilizes loads as low as 20-40% of an individual's 1-RM for 2-4 sets of exercise to or near volitional failure. BFR is usually maintained between sets with a total restriction time of 5-10 minutes [12] (Box 3).

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“…ACE2 is also expressed in hematopoietic stem and progenitor cells [6]. ACE2 stimulates mobilization of progenitor cells from bone marrow, migration to areas of vascular damage and revascularization of ischemic areas in pathological conditions like hypoxic exercise [6][7][8]. SARS-CoV-2 also probably invades host cells via CD147 (also known as Basigin or EMMPRIN) [9].…”

Section: Introductionmentioning

confidence: 99%

Is COVID-19 a New Hematologic Disease?

Debuc

Smadja

2020

Stem Cell Rev and Rep

109

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SARS-CoV-2 viruses are positive single-stranded RNA viruses, whose infection can be asymptomatic or lead to the coronavirus disease 2019 . Covid-19 is a respiratory infection with a significant impact on the hematopoietic system and hemostasis leading to several cardiovascular complications. Hematologic consequences of this new infection allowed medical community to start new treatment approaches concerning infection going from targeted anti-inflammatory drugs to anticoagulation or stem cell therapies. A better understanding of Covid-19 pathophysiology, in particular hematological disorders, will help to choose appropriate treatment strategies.

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Blood flow restriction exercise stimulates mobilization of hematopoietic stem/progenitor cells and increases the circulating ACE2 levels in healthy adults

Cited by 19 publications

References 44 publications

Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers

Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers

Effects of Blood Flow Restriction Exercise and Possible Applications in Type 2 Diabetes

Is COVID-19 a New Hematologic Disease?

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