Muscle cell derived angiopoietin-1 contributes to both myogenesis and angiogenesis in the ischemic environment

McClung, Joseph M.; Reinardy, Jessica L.; Mueller, Sarah B.; McCord, Timothy J.; Kontos, Christopher D.; Brown, David A.; Hussain, Sabah N. A.; Schmidt, Cameron A.; Ryan, Terence E.; Green, Thomas D.

doi:10.3389/fphys.2015.00161

Cited by 30 publications

(28 citation statements)

References 60 publications

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“…Recent evidence from our group and others supports the idea that skeletal muscle responses to tissue ischemia, and not solely the vascular supply, play an important role in determining the muscle response to limb ischemia (9)(10)(11)(12). In mice subjected to hind limb ischemia (HLI), a model of PAD, the genetic background strongly influences outcomes.…”

Section: Introductionmentioning

confidence: 72%

Muscle progenitor cells are required for the regenerative response and prevention of adipogenesis after limb ischemia

Abbas

Olivere

Padgett

et al. 2020

Preprint

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Peripheral artery disease (PAD) is nearly as common as coronary artery disease, but few effective treatments exist, and it is associated with significant morbidity and mortality. Although PAD studies have focused on the vascular response to ischemia, skeletal muscle cells play a critically important role in determining the phenotypic manifestation of PAD. Here, we demonstrate that genetic ablation of Pax7 + muscle progenitor cells (MPCs, or satellite cells) in a murine model of hind limb ischemia (HLI) resulted in a complete absence of normal muscle regeneration following ischemic injury, despite a lack of morphological or physiological changes in resting muscle. Compared to ischemic muscle of control mice (Pax7 WT ), the ischemic limb of Pax7-deficient mice (Pax7 ∆ ) was unable to generate significant force 7-or 28-days after HLI in ex vivo force measurement studies. A dramatic increase in adipose infiltration was observed 28 days after HLI in Pax7 ∆ mice, which replaced functional muscle. To investigate the mechanism of this adipogenic change, mice with inhibition of fibro/adipogenic precursors (FAPs), another pool of MPCs, were subjected to HLI. Inhibition of FAPs decreased muscle adipose fat but increased fibrosis. MPCs cultured from mouse muscle tissue failed to form myotubes in vitro following depletion of satellite cells in vivo, and they displayed an increased propensity to differentiate into fat in adipogenic medium. Importantly, this phenotype was recapitulated in patients with critical limb ischemia (CLI), the most severe form of PAD. Skeletal muscle samples from CLI patients demonstrated an increase in adipose deposition in more ischemic regions of muscle, which corresponded with a decrease in the number of satellite cells in those regions.Collectively, these data demonstrate that Pax7 + MPCs are required for normal muscle regeneration after ischemic injury, and they suggest that targeting muscle regeneration may be an important therapeutic approach to prevent muscle degeneration in PAD.

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Section: Introductionmentioning

confidence: 72%

Muscle progenitor cells are required for the regenerative response and prevention of adipogenesis after limb ischemia

Abbas

Olivere

Padgett

et al. 2020

Preprint

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“…The heat map of those factors suggests that their amount increases several fold in platelet releasate resulting in two clusters of moderate and higher intensity respectively. Of note, the factors SCF, FGF‐β, HGF, HER2, Follistatin, VEGFR‐1, EGFR, PDGF‐AB and PDGF‐BB (known to regulate proliferation) and VEGFR‐2, IL‐6, TIE‐2 and HB‐EGF (known to induce differentiation) showed a 4‐20‐fold increase in the TRAP6‐activated platelet releasate as compared to unstimulated platelets. EGF, FGF, VEGF and PDGF‐BB have been shown to promote myoblast proliferation and consistently inhibit myogenic differentiation, while VEGFR2 expression is increased during differentiation .…”

Section: Discussionmentioning

confidence: 99%

Platelet releasate promotes skeletal myogenesis by increasing muscle stem cell commitment to differentiation and accelerates muscle regeneration following acute injury

et al. 2018

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Aim:The use of platelets as biomaterials has gained intense research interest.However, the mechanisms regarding platelet-mediated skeletal myogenesis remain to be established. The aim of this study was to determine the role of platelet releasate in skeletal myogenesis and muscle stem cell fate in vitro and ex vivo respectively. Methods: We analysed the effect of platelet releasate on proliferation and differentiation of C2C12 myoblasts by means of cell proliferation assays, immunohistochemistry, gene expression and cell bioenergetics. We expanded in vitro findings on single muscle fibres by determining the effect of platelet releasate on murine skeletal muscle stem cells using protein expression profiles for key myogenic regulatory factors. Results: TRAP6 and collagen used for releasate preparation had a more pronounced effect on myoblast proliferation vs thrombin and sonicated platelets (P < 0.05). In addition, platelet concentration positively correlated with myoblast proliferation. Platelet releasate increased myoblast and muscle stem cell proliferation in a dose-dependent manner, which was mitigated by VEGFR and PDGFR inhibition. Inhibition of VEGFR and PDGFR ablated MyoD expression on proliferating muscle stem cells, compromising their commitment to differentiation in muscle fibres (P < 0.001). Platelet releasate was detrimental to myoblast fusion and affected differentiation of myoblasts in a temporal manner. Most importantly, we show that platelet releasate promotes skeletal myogenesis through the PDGF/ VEGF-Cyclin D1-MyoD-Scrib-Myogenin axis and accelerates skeletal muscle regeneration after acute injury. Conclusion: This study provides novel mechanistic insights on the role of platelet releasate in skeletal myogenesis and set the physiological basis for exploiting platelets as biomaterials in regenerative medicine. K E Y W O R D Sgrowth factors, platelet releasate, platelet-rich plasma, regeneration, satellite cells, skeletal muscle

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“…Although the importance of angiopoietin signaling in the vasculature is well defined, the cellular origins and functional roles of these two factors in skeletal muscle have only recently received attention. ANGPT1 is the principal angiopoietin produced by skeletal myoblasts and myotubes and is an important regulator of myogenesis and angiogenesis (38,42). Conversely, ANGPT2 has no effect on myoblast proliferation and migration and exerts a relatively weak and context-dependent effect on angiogenesis (41).…”

Section: Skeletal Muscle Angiogenic Signalingmentioning

confidence: 99%

Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle

Kuhlenhoelter

Kim

Neff

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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Heat therapy has been shown to promote capillary growth in skeletal muscle and in the heart in several animal models, but the effects of this therapy on angiogenic signaling in humans are unknown. We evaluated the acute effect of lower body heating (LBH) and unilateral thigh heating (TH) on the expression of angiogenic regulators and heat shock proteins (HSPs) in healthy young individuals. Exposure to LBH ( n = 18) increased core temperature (Tc) from 36.9 ± 0.1 to 37.4 ± 0.1°C ( P < 0.01) and average leg skin temperature (Tleg) from 33.1 ± 0.1 to 39.6 ± 0.1°C ( P < 0.01), but did not alter the levels of circulating angiogenic cytokines and bone marrow-derived proangiogenic cells (CD34+CD133+). In skeletal muscle, the change in mRNA expression from baseline of vascular endothelial growth factor (VEGF), angiopoietin 2 (ANGPT2), chemokines CCL2 and CX3CL1, platelet factor-4 (PF4), and several members of the HSP family was higher 30 min after the intervention in the individuals exposed to LBH ( n = 11) compared with the control group ( n = 12). LBH also reduced the expression of transcription factor FOXO1 ( P = 0.03). Exposure to TH ( n = 14) increased Tleg from 32.8 ± 0.2 to 40.3 ± 0.1°C ( P < 0.05) but Tc remained unaltered (36.8 ± 0.1°C at baseline and 36.9 ± 0.1°C at 90 min). This intervention upregulated the expression of VEGF, ANGPT1, ANGPT2, CCL2, and HSPs in skeletal muscle but did not affect the levels of CX3CL1, FOXO-1, and PF4. These findings suggest that both LBH and TH increase the expression of factors associated with capillary growth in human skeletal muscle.

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Muscle cell derived angiopoietin-1 contributes to both myogenesis and angiogenesis in the ischemic environment

Cited by 30 publications

References 60 publications

Muscle progenitor cells are required for the regenerative response and prevention of adipogenesis after limb ischemia

Muscle progenitor cells are required for the regenerative response and prevention of adipogenesis after limb ischemia

Platelet releasate promotes skeletal myogenesis by increasing muscle stem cell commitment to differentiation and accelerates muscle regeneration following acute injury

Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle

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