The Role of Midkine in Arteriogenesis, Involving Mechanosensing, Endothelial Cell Proliferation, and Vasodilation

Weckbach, Ludwig T.; Preissner, Klaus T.; Deindl, Elisabeth

doi:10.3390/ijms19092559

Cited by 38 publications

(32 citation statements)

References 116 publications

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“…Given that GH is a major regulator of eNOS expression and NO production in ECs for vasodilation that typically increases VEGF and KDR, and as a consequence of its participation in vascular homeostasis, it is tempting to speculate that both MK and GH might work together to maintain vascular homeostasis, as well as to activate vascular enlargement when an ischemic condition is present. MK could indirectly promote vasodilation by increasing the bioavailability of GH in ECs [168]. However, this hypothesis is not yet proved and needs confirmation.…”

Section: Gh and Midkine (Mdk) Relation Should Be Investigatedmentioning

confidence: 96%

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

Caicedo

Devesa²,

Álvarez

et al. 2020

Cells

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Despite the important role that the growth hormone (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 is considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effects, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy is described. All the elements that trigger the local and systemic production of GH/IGF-I, as well as their possible roles both in physiological and pathological conditions are analyzed. All of the evidence is combined with important data from the GHAS trial, in which GH or a 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 ischemic disease.

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Section: Gh and Midkine (Mdk) Relation Should Be Investigatedmentioning

confidence: 96%

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

Caicedo

Devesa²,

Álvarez

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Given that GH is a major regulator of eNOS expression and NO production in ECs for vasodilation, that typically increases VEGF and KDR, and as a consequence of its participation in vascular homeostasis, it is tempting to speculate that both MK and GH might work together to maintain vascular homeostasis, and also to activate vascular enlargement when an ischemic condition is present. MK could promote vasodilation indirectly by increasing the bioavailability of GH in ECs [189]. However, this hypothesis is not yet proved and needs confirmation.…”

Section: Gh and Mesenchymal Stem Cells (Mscs)mentioning

confidence: 95%

“…MK seems to be secreted by follicle stimulating cells, controlling GH production from GH cells in a paracrine way via protein tyrosine phosphatase receptor-type Z (Ptprz1) [188]. MK is involved in the process of mechanosensing to SSF, as its receptor has an identical structure of sensors for laminar shear stress and induces a very similar signal cascades [189]. A mechanosensing mechanism has been proposed for collateral enlargement with the main participation of several molecules such as PECAM-1, VE-Cadherin or VEGFR2/KDR [190], to which, in our opinion, GH/IGF-I should be added, as it has been demonstrated at the beginning of the text.…”

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

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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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“…44,45 And the heterotrimeric G-proteins, in combination with seven transmembrane receptors, also participate in fluid shear stress-initiated signaling cascades via interactions with other mechanosensors. 46 For instance, the Gq/G11 protein, which forms a heparan sulfates-stabilized complex with PECAM-1, 47 mediates the activation of the endothelial mechanosensory complex consisting of PECAM-1, VE-cadherin, VEGRR2, and PECAM-1. In this complex, the direct transducer of shear stress is vital for Src family F I G U R E 1 The simplified hemodynamic patterns of collateral arterioles in ideal laminar conditions.…”

Section: The Role Of Fss In Arteriogenesismentioning

confidence: 99%

The hydromechanics in arteriogenesis

Bai

2020

Aging Medicine

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Increasing age has been identified as an independent risk factor for the incidence of coronary atherosclerosis. According to an age-period-cohort analysis of acute myocardial infarction (AMI) in China from 1987 to 2014, population aging has contributed to a steep elevation in mortality due to AMI since 2004. 1 In terms of elderly patients (more prone to diffused coronary stenosis or multivessel disease), the maximally beneficial results of current strategies, including interventional or surgical revascularization (percutaneous coronary interventions [PCI] and coronary artery bypass graft [CABG]), are limited. Even though PCI improved the clinical outcomes in acute coronary syndromes (ACS) significantly, it was related to a higher incidence of myocardial infarction in stable multivessel coronary disease. 2 And the application of coronary artery bypass graft surgery in the elderly is restrained by its strict indications, surgical stress, perioperative complications, and needs for specific caregiving programs. 3 Thus, promoting the formation of coronary collateral circulation through medicine or physical therapy to compensate for myocardial hypoperfusion might be a novel therapeutic strategy for coronary heart diseases in elderly patients. Arteriogenesis, the primary process of collateral development, has been found to play an essential role in the compensation of ischemic vascular diseases, including myocardial ischemia, stroke, and other peripheral vascular diseases. 4 Taking myocardial infarction, which is usually caused by coronary atherosclerosis, as an example: because the anatomical features of coronary vessels with their interconnections among arteries form an anastomotic network, it is possible to alleviate the clinical symptoms of myocardial ischemia by developing compensating arteries from pre-existent anastomotic arterioles. 5 According to clinical research, associations have been observed between the formation of collateral circulation and the severity of coronary ischemic events. 5 However, in addition to its heterogeneity among patients, the process of arteriogenesis also

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The Role of Midkine in Arteriogenesis, Involving Mechanosensing, Endothelial Cell Proliferation, and Vasodilation

Cited by 38 publications

References 116 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

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

The hydromechanics in arteriogenesis

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