Denervation in Femoral Artery-Ligated Hindlimbs Diminishes Ischemic Recovery Primarily via Impaired Arteriogenesis

Cen, Yinghuan; Liu, Junfeng; Qin, Yuansen; Liu, Ruiming; Wang, Huijin; Zhou, Yu; Wang, Shenming; Hu, Zhiqiang

doi:10.1371/journal.pone.0154941

Cited by 13 publications

(15 citation statements)

References 46 publications

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“…GH and NO-independent vascular tone: The role of sympathetic system Sympathetic innervation seems to be necessary for stabilizing vascular wall tone and cells phenotype, since in sympathectomized vessels both SMCs and fibroblasts increase in numbers, with collagen alterations (collagen III upregulation and collagen IV downregulation). This supports the hypothesis that the autonomic system participates in vascular homeostasis [180]. In GHD patients a marked increase in sympathetic activity has been found [181], but it tends to be reversed after GH replacement therapy [182], suggesting that the hormone may regulate central sympathetic activity, affecting vascular peripheral resistance.…”

Section: Gh and Mesenchymal Stem Cells (Mscs)supporting

confidence: 77%

“…In GHD patients a marked increase in sympathetic activity has been found [181], but it tends to be reversed after GH replacement therapy [182], suggesting that the hormone may regulate central sympathetic activity, affecting vascular peripheral resistance. When sympathetic activity is increased collaterals will suffer an intimal thickening that diminishes SSF and collateral enlargement after ischemia [180]. An increased vasomotor tone has been described in skeletal muscle arterioles in diabetic patients with neuropathy, and a higher α-adrenergic tone has been found in the iliac artery of diabetic animals [183,184].…”

Section: Gh and Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

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Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

Caicedo¹,

Devesa²,

Álvarez³

et al. 2019

Preprint

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Despite the important role that the GH/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium has turned to be considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effect, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, it will be described the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy. It will be analyzed all those elements triggering the local and systemic production of GH/IGF-I and their possible role both in physiological and pathological conditions. The whole evidence will be combined with important data from the GHAS trial, in which GH or placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of the ischemic disease.A normal embryonic development needs the formation of blood vessels [21]; after birth there is also the need of the formation of new blood vessels while growing, but also in some physiological processes such as the menstrual cycle in women and the development of the mammary gland during pregnancy [22], but apart from these situations, adult neovascularization rarely takes place and when it happens it is associated with pathological affectations, such as wounds, muscle injuries, fractures or hypoxia/ischemia. The question now would be: how does neovascularization occur in adults and what is the role of the GH / IGF-I system in it?As it seems logical, hypoxia is a very important stimulus for the growth of new blood vessels [23], triggering this growth through hypoxia-inducible factors (HIF) that act on the expression of proangiogenic factors, but also that of anti-angiogenic factors to achieve the perfect number and size of the vessels necessary to compensate for the lack of oxygen supply and to regenerate the tissue [23]. This is a clear and well-established fact for angiogenesis. However, when a progressive narrowing of the vascular lumen appears, preexisting collaterals will have to growth to compensate the lack of distal flow which is triggered in a totally different way. With independence of that, the stimulation of endothelial nitric oxide synthase (eNOS) that leads to the production of nitric oxide (NO) from the vascular endothelium seems to be the key mediator for both kind of reparative processes. NO is a potent vasodilator, therefore increasing blood supply to the zone affected by hypoxia/ischemia. This implies changes in the vascular tone, vasorelaxation and vasopermeability, which are affected in arteries suffering an atherosclerotic damage. Interestingly, GH activates the NO pathway [14,24] throughout direct mechanisms tha...

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Section: Gh and Mesenchymal Stem Cells (Mscs)supporting

confidence: 77%

Section: Gh and Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

Caicedo¹,

Devesa²,

Álvarez³

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…[1][2][3] Muscle atrophy impairs quality of life, and it complicates treatment and recovery. [11][12][13][14][15] IGF1 has multiple isoforms that vary in potency and tissue localization. 6,7 IGF1 increases muscle mass by increasing satellite cell proliferation, enhancing myoblast differentiation, and inducing skeletal muscle cell hypertrophy, making it a well-suited target for treating muscle atrophy.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 Furthermore, IGF1 prevents the loss of muscle mass by reducing atrophy-related signaling in muscle cells, 10 and it promotes blood vessel growth, inhibits apoptosis, and increases neurite outgrowth. [11][12][13][14][15] IGF1 has multiple isoforms that vary in potency and tissue localization. 14,16,17 The IGF1 gene, which is highly conserved between humans (IGF1) and mice (Igf1), has six exons.…”

Section: Introductionmentioning

confidence: 99%

CRISPR‐Cas9–induced IGF1 gene activation as a tool for enhancing muscle differentiation via multiple isoform expression

Roberston

Raghunathan

Potaman³

et al. 2019

The FASEB Journal

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Muscle wasting, or muscle atrophy, can occur with age, injury, and disease; it affects the quality of life and complicates treatment. Insulin-like growth factor 1 (IGF1) is a key positive regulator of muscle mass. The IGF1/Igf1 gene encodes multiple protein isoforms that differ in tissue expression, potency, and function, particularly in cellular proliferation and differentiation, as well as in systemic versus localized signaling. Genome engineering is a novel strategy for increasing gene expression and has the potential to recapitulate the diverse biology seen in IGF1 signaling through the overexpression of multiple IGF1 isoforms. Using a CRISPR-Cas9 gene activation approach, we showed that the expression of multiple IGF1 or Igf1 mRNA variants can be increased in human and mouse skeletal muscle myoblast cell lines using a single-guide RNA (sgRNA). We found increased IGF1 protein levels in the cell culture media and increased cellular phosphorylation of AKT1, the main effector of IGF1 signaling. We also showed that the expression of Class 1 or Class 2 mRNA variants can be selectively increased by changing the sgRNA target location. The expression of multiple IGF1 or Igf1 mRNA transcript variants in human and mouse skeletal muscle myoblasts promoted myotube differentiation and prevented dexamethasoneinduced atrophy in myotubes in vitro. Our findings suggest that this novel approach for enhancing IGF1 signaling has potential therapeutic applications for treating skeletal muscle atrophy. K E Y W O R D Sgene regulation, insulin-like growth factor 1, muscle atrophy 556 |

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“…For decades, the mechanisms responsible for arteriogenesis was generally accepted as fluid shear stress, inflammation, the proliferation of vascular cells, and the participation of cytokines (Deindl et al, ). Recently, much evidence has accumulated suggesting that neural regulation might also be an important contributor to arteriogenesis (Mukouyama et al, ; Cen et al, ). Our previous data showed that denervation impaired collateral vessel growth, suggesting that innervation plays an important role in rat/rabbit hind limb of arteriogenesis after femoral artery ligature (Luo et al, ).…”

mentioning

confidence: 99%

The Neuropeptide Secretoneurin Exerts a Direct Effect on Arteriogenesis In Vivo and In Vitro

Liu

Wang

Zhao

et al. 2018

The Anatomical Record

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It is well known that nerves modulate the development and remodeling of blood vessels by releasing different neuropeptides and neurotransmitters. Secretoneurin (SN), a neuropeptide located in nerve fibers along blood vessels, acts as a pro‐angiogenic agent and induces postnatal vasculogenesis. However, little is known about its involvement in arteriogenesis. In the present study, we tested the hypothesis that SN promotes arteriogenesis in a rat model of hind limb ischemia, as such, we evaluated the effect of this neuropeptide on proliferation and the production of adhesion and chemotaxis molecules in vascular smooth muscle cells (VSMCs), the main component that carries the burden of the transformation of a small arteriole into a large collateral vessel. In vivo, SN‐immunoreactive nerve fibers were abundantly distributed in the adventitia of the collateral vessel. Moreover, administration of SN induced cell proliferation in the vascular wall and the infiltration of inflammatory cells/macrophages to promote collateral vessel growth. This was shown by an increased density of arterioles/arteries, together with a well‐developed network of collateral vessels, and well‐preserved skeletal muscles. In vitro, SN exerted proliferative effects on VSMCs and stimulated these cells to express adhesion molecules. In conclusion, our data demonstrate for the first time that SN acts as a mediator of inflammation, contributing to collateral vessel growth, in addition to directly stimulating cell proliferation in the vascular wall to promote collateral vessel growth in a rat model of hind limb ischemia. Anat Rec, 301:1917–1927, 2018. © 2018 Wiley Periodicals, Inc.

show abstract

Denervation in Femoral Artery-Ligated Hindlimbs Diminishes Ischemic Recovery Primarily via Impaired Arteriogenesis

Cited by 13 publications

References 46 publications

Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

CRISPR‐Cas9–induced IGF1 gene activation as a tool for enhancing muscle differentiation via multiple isoform expression

The Neuropeptide Secretoneurin Exerts a Direct Effect on Arteriogenesis In Vivo and In Vitro

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