Propranolol increases vascular permeability through pericyte apoptosis and exacerbates oxygen-induced retinopathy

Yun, Jeong‐Ho; Koh, Young Jun; Jeong, Han Seok; Lee, Da Hye; Lee, Eun Hui; Cho, Chung Hyun

doi:10.1016/j.bbrc.2018.08.041

Cited by 12 publications

(7 citation statements)

References 24 publications

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“…In line with the state-of-the-art histological assessment, a detailed flow cytometry analysis revealed an increased percentage of bona fide skeletal muscle ECs, defined as CD45 − CD31 + CD34 + Sca-1 + cells (arterial, capillary, and venular ECs) [ 55 ] in dystrophic mice, together with a diminished percentage of pericytes, pivotal for the maintenance of blood vessels, as their deficiency may result in increased vascular permeability [ 56 , 57 ]. Taking into account published reports on defects in ECs in animal models of DMD and DMD patients related to both morphological alterations and properties [ 11 ], we put into the question proper functionality of mdx blood vessels, as reflected by diminished blood flow and blood flow recovery after FAL.…”

Section: Discussionmentioning

confidence: 99%

Age-Dependent Dysregulation of Muscle Vasculature and Blood Flow Recovery after Hindlimb Ischemia in the mdx Model of Duchenne Muscular Dystrophy

et al. 2021

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Duchenne muscular dystrophy (DMD), caused by a lack of functional dystrophin, is characterized by progressive muscle degeneration. Interestingly, dystrophin is also expressed in endothelial cells (ECs), and insufficient angiogenesis has already been hypothesized to contribute to DMD pathology, however, its status in mdx mice, a model of DMD, is still not fully clear. Our study aimed to reveal angiogenesis-related alterations in skeletal muscles of mdx mice compared to wild-type (WT) counterparts. By investigating 6- and 12-week-old mice, we sought to verify if those changes are age-dependent. We utilized a broad spectrum of methods ranging from gene expression analysis, flow cytometry, and immunofluorescence imaging to determine the level of angiogenic markers and to assess muscle blood vessel abundance. Finally, we implemented the hindlimb ischemia (HLI) model, more biologically relevant in the context of functional studies evaluating angiogenesis/arteriogenesis processes. We demonstrated that both 6- and 12-week-old dystrophic mice exhibited dysregulation of several angiogenic factors, including decreased vascular endothelial growth factor A (VEGF) in different muscle types. Nonetheless, in younger, 6-week-old mdx animals, neither the abundance of CD31+α-SMA+ double-positive blood vessels nor basal blood flow and its restoration after HLI was affected. In 12-week-old mdx mice, although a higher number of CD31+α-SMA+ double-positive blood vessels and an increased percentage of skeletal muscle ECs were found, the abundance of pericytes was diminished, and blood flow was reduced. Moreover, impeded perfusion recovery after HLI associated with a blunted inflammatory and regenerative response was evident in 12-week-old dystrophic mice. Hence, our results reinforce the hypothesis of age-dependent angiogenic dysfunction in dystrophic mice. In conclusion, we suggest that older mdx mice constitute an appropriate model for preclinical studies evaluating the effectiveness of vascular-based therapies aimed at the restoration of functional angiogenesis to mitigate DMD severity.

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Section: Discussionmentioning

confidence: 99%

Age-Dependent Dysregulation of Muscle Vasculature and Blood Flow Recovery after Hindlimb Ischemia in the mdx Model of Duchenne Muscular Dystrophy

et al. 2021

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“…The stimulatory effects of isoprenaline are VEGFR2-dependent and are inhibited by both β 1 and β 2 AR antagonists, with the effects of the β 2 AR antagonists being more prominent [55]. Many β blockers, such as propranolol, have high affinities for β 3 ARs and accumulating evidence suggests that the β 3 ARs may play a major role in the pathophysiology of infantile hemangioma [56].…”

Section: Involvement Of β Ars In Angiogenesis-related Pathologies-evi...mentioning

confidence: 99%

A Systematic Review on the Role of Adrenergic Receptors in Angiogenesis Regulation in Health and Disease

Xanthopoulos¹,

Daskalopoulou²,

Frountzi³

et al. 2021

IJTM

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Angiogenesis is essential during development or when tissue restoration and oxygenation is required. Limited or excessive formation of blood vessels is a hallmark of several pathologies, and many angiogenesis-related pathways are being studied to highlight potential targets for effective angiogenesis-stimulating or inhibiting therapeutic approaches. A few studies point to the adrenergic system as a significant regulator of angiogenesis, directly or indirectly. Functional adrenergic receptors are expressed on endothelial cells and affect their response to the adrenergic system. The latter can also upregulate the release of growth factors by mural cells of the vessel wall, blood cells or cancer cells, thus subsequently affecting endothelial cell functions and angiogenesis. In the present study we summarize up-to-date literature on the known effects of the adrenergic receptors on physiological and pathological angiogenesis.

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“…Pericytes tighten the tight junction of ECs to reduce endothelial permeability. They play an important role in maintaining the integrity of the inner blood-retinal barrier (BRB) by surrounding ECs [73]. One study found that the pericyte survival increases and the vascular permeability observed in the diabetic retinas of mice decreases [74].…”

Section: Protective Effect Of Pedf Onmentioning

confidence: 99%

Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization

2020

Oxidative Medicine and Cellular Longevity

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Choroidal neovascularization (CNV) is a sight-threatening disease and is characterized by the formation of pathological neovascularization in the choroid which extends into the subretinal space. Exudative age-related macular degeneration (AMD) is the formation of CNV in the macular area which leads to irreversible blindness. Continuous leakage and hemorrhage of the CNV lesion may eventually result in scarring or later fibrosis, which could result in photoreceptor cell atrophy. The current strategy for treating CNV is the use of antivascular endothelial growth factor (VEGF) agents. Many studies have demonstrated the efficacy of intravitreal anti-VEGF therapy. Other studies have also reported the side effects of single anti-VEGF treatment. And long-term inhibition of a single system may result in collateral damage to other visual elements. Pigment epithelium-derived factor (PEDF) is a 50 kDa protein that was first isolated from the conditioned medium of human RPE cells. PEDF has both antiangiogenesis and neuroprotective functions for photoreceptor cells. It may be a potential ocular antiangiogenic agent. This review outlines the distribution of PEDF in the eye, the mechanism of antiangiogenesis, the protective effect on the retina, and the relationship between PEDF and VEGF.

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Propranolol increases vascular permeability through pericyte apoptosis and exacerbates oxygen-induced retinopathy

Cited by 12 publications

References 24 publications

Age-Dependent Dysregulation of Muscle Vasculature and Blood Flow Recovery after Hindlimb Ischemia in the mdx Model of Duchenne Muscular Dystrophy

Age-Dependent Dysregulation of Muscle Vasculature and Blood Flow Recovery after Hindlimb Ischemia in the mdx Model of Duchenne Muscular Dystrophy

A Systematic Review on the Role of Adrenergic Receptors in Angiogenesis Regulation in Health and Disease

Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization

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