COL4A1 Mutation as a Cause of Familial Recurrent Intracerebral Hemorrhage

Campo‐Caballero, David; Rodríguez‐Antigüedad, Jon; Ekiza-Bazan, Jon; Iruzubieta, Pablo; Fernández‐Eulate, Gorka; Muñoz-Lopetegui, Amaia; Martínez-Zabaleta, Maite; Riva, Patricia de la; Urtasun-Ocariz, Miguel Ángel; Munáin, Adolfo López de; Arce, Ana de

doi:10.1016/j.jstrokecerebrovasdis.2020.104652

Cited by 6 publications

(6 citation statements)

References 3 publications

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“…COL41 mutations could inhibit type IV collagen deposits in the basement membrane of capillaries, resulting in disruption of capillaries and multisystem small vessel diseases. 39 Consistently, silencing of COL4A1 attenuated the inhibiting effects of miR-543 inhibition on the proliferation, migration, invasion, and angiogenesis of CMEC, indicating that miR-543 affected CMECs through downregulating COL4A1 expression. In the in vivo experiment, hMSC-Exo was demonstrated to elevate miR-543 expression and block COL4A1 expression in myocardial tissues, which implied that hMSCs-Exo might carry miR-543 into myocardial tissues to downregulate COL4A1 expression, thus preventing MIinduced cardiac dysfunction.…”

Section: Discussionmentioning

confidence: 76%

“…Moreover, silencing of COL4A1 markedly promoted the proliferation, migration, invasion, and angiogenesis of hypoxia‐treated CMECs. COL41 mutations could inhibit type IV collagen deposits in the basement membrane of capillaries, resulting in disruption of capillaries and multisystem small vessel diseases 39 . Consistently, silencing of COL4A1 attenuated the inhibiting effects of miR‐543 inhibition on the proliferation, migration, invasion, and angiogenesis of CMEC, indicating that miR‐543 affected CMECs through downregulating COL4A1 expression.…”

Section: Discussionmentioning

confidence: 87%

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miR‐543 in human mesenchymal stem cell–derived exosomes promotes cardiac microvascular endothelial cell angiogenesis after myocardial infarction through COL4A1

et al. 2021

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To explore the impact and mechanism of human mesenchymal stem cells (hMSCs) on the angiogenesis of cardiac microvascular endothelial cells (CMECs) after ischemia insult. Exosomes derived from hMSCs (hMSCs‐Exo) were identified by Western blotting and labeled by PHK‐67. CMECs were isolated from rat myocardial tissues. After hypoxic treatment, CMECs were cultured with hMSCs and exosome inhibitor (GW4869) or transfected with si‐COL4A1 + miR‐543 inhibitor. CMEC proliferation, migration, invasion, and angiogenesis were examined. Target genes of miR‐543 were predicted and then were identified by dual luciferase assay. Myocardial infarction (MI) rat model established by suture occlusion was intravenously injected with hMSCs‐Exo. Fluorescence microscope was applied to visualize exosomes in myocardial tissues. Infarction volume and pathologies of myocardial tissues were observed. Ki‐67 and miR‐543 expressions were detected. The isolated hMSC‐Exo expressed TSG101, HSP70, and CD63. Hypoxia‐treated CMECs cultured with hMSCs exhibited high proliferation, migration, invasion, and angiogenesis ability, while incubation with exosome inhibitor GW4969 offset the promoting effects of hMSCs on the proliferation, migration, invasion, and angiogenesis of CMECs. hMSCs transfected with miR‐543 inhibitor brought CMECs weak viability and angiogenesis ability. CMECs transfected with si‐COL4A1 and miR‐543 inhibitor showed low proliferation, migration, invasion, and angiogenesis compared to those transfected with si‐COL4A1 alone. hMSCs‐Exo entered the myocardial tissues of MI rats. Injection of hMSCs‐Exo in MI rats diminished infarction size, attenuated MI‐induced injuries, and increased Ki‐67 expression. hMSCs‐Exo facilitates the proliferation, migration, invasion, and angiogenesis of CMECs through transferring miR‐543 and downregulating COL4A1 expression.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 87%

miR‐543 in human mesenchymal stem cell–derived exosomes promotes cardiac microvascular endothelial cell angiogenesis after myocardial infarction through COL4A1

et al. 2021

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“…56 COL41 mutations could inhibit type IV collagen deposits in the basement membrane of capillaries, resulting in disruption of capillaries and multisystem small vessel diseases. 57 This reduction in COL4A1 expression leads to enhanced proliferation, migration, invasion and angiogenesis in the CMECs. 39 Additionally, bone marrow-derived mesenchymal stem (BMSC)-derived exosomes overexpressing mir-126 promote diffusion, migration and angiogenesis in HUVECs by inhibiting PIK3R2 to activate the vascular endothelial growth factor (VEGF) and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways.…”

Section: Promoting Angiogenesismentioning

confidence: 99%

“…Another study showed that MSC‐derived exosomes transfer mir‐543 to co‐cultured hypoxic cardiac microvascular endothelial cells (CMECs), resulting in reduced expression of COL4A1, a major component of the vascular basement membrane 56 . COL41 mutations could inhibit type IV collagen deposits in the basement membrane of capillaries, resulting in disruption of capillaries and multisystem small vessel diseases 57 . This reduction in COL4A1 expression leads to enhanced proliferation, migration, invasion and angiogenesis in the CMECs 39 .…”

Section: The Role Of Msc‐derived Exosomes In the Treatment Of Myocard...mentioning

confidence: 99%

Mesenchymal stem cell‐derived exosomes in myocardial infarction: Therapeutic potential and application

Li,

Tang,

Yin

et al. 2023

The Journal of Gene Medicine

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Myocardial infarction refers to the irreversible impairment of cardiac function resulting from the permanent loss of numerous cardiomyocytes and the formation of scar tissue. This condition is caused by acute and persistent inadequate blood supply to the heart's arteries. In the treatment of myocardial infarction, Mesenchymal stem cells (MSCs) play a crucial role because of their powerful therapeutic effects.These effects primarily stem from the paracrine secretion of multiple factors by MSCs, with exosome‐carried microRNAs being the most effective component in promoting cardiac function recovery after infarction. Exosome therapy has emerged as a promising cell‐free treatment for myocardial infarction as a result of its relatively simple composition, low immunogenicity and controlled transplantation dose. Despite these advantages, maintaining the stability of exosomes after transplantation and enhancing their targeting effect remain significant challenges in clinical applications. In recent developments, several approaches have been designed to optimize exosome therapy. These include enhancing exosome retention, improving their ability to target specific effects, pretreating MSC‐derived exosomes and employing transgenic MSC‐derived exosomes. This review primarily focuses on describing the biological characteristics of exosomes, their therapeutic potential and their application in treating myocardial infarction.

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“…145 COL4 mutations can be related to intracerebral subcortical hemorrhages or microhemorrhages and severe SVD. 146 Other genetically mediated cerebral small vessel disease disorders, which can be associated with dementia, include: collagen type IV mutations, forkhead box C1 mutations and hereditary cerebral amyloid CAA. 147 Hereditary CAA, associated with both ischemic and hemorrhagic stroke, is associated with amyloid precursor protein (APP) mutations.…”

Section: Genetic Factors Involved In Vadmentioning

confidence: 99%

Emerging Concepts in Vascular Dementia: A Review

Bir

Khan

Javalkar

et al. 2021

Journal of Stroke and Cerebrovascular Diseases

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Objective: Vascular dementia (VaD) is the second most common cause of dementia and a major health concern worldwide. A comprehensive review on VaD is warranted for better understanding and guidance for the practitioner. We provide an updated overview of the epidemiology, pathophysiological mechanisms, neuroimaging patterns as well as current diagnostic and therapeutic approaches. Materials and methods: A narrative review of current literature in VaD was performed based on publications from the database of PubMed, Scopus and Google Scholar up to January, 2021. Results: VaD can be the result of ischemic or hemorrhagic tissue injury in a particular region of the brain which translates into clinically significant cognitive impairment. For example, a cerebral infarct in the speech area of the dominant hemisphere would translate into clinically significant impairment as would involvement of projection pathways such as the arcuate fasciculus. Specific involvement of the angular gyrus of the dominant hemisphere, with resultant Gerstman's syndrome, could have a pronounced effect on functional ability despite being termed a "minor stroke". Small vessel cerebrovascular disease can have a cumulate effect on cognitive function over time. It is unfortunately well recognized that "good" functional recovery in acute ischemic or haemorrhagic stroke, including subarachnoid haemorrhage, does not necessarily translate into good cognitive recovery. The victim may often be left unable to have gainful employment, drive a car safely or handle their affairs independently. Conclusions: This review should serve as a compendium of updated information on VaD and provide guidance in terms of newer diagnostic and potential therapeutic approaches.

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COL4A1 Mutation as a Cause of Familial Recurrent Intracerebral Hemorrhage

Cited by 6 publications

References 3 publications

miR‐543 in human mesenchymal stem cell–derived exosomes promotes cardiac microvascular endothelial cell angiogenesis after myocardial infarction through COL4A1

miR‐543 in human mesenchymal stem cell–derived exosomes promotes cardiac microvascular endothelial cell angiogenesis after myocardial infarction through COL4A1

Mesenchymal stem cell‐derived exosomes in myocardial infarction: Therapeutic potential and application

Emerging Concepts in Vascular Dementia: A Review

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