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Associations of MicroRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism—An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) remains the leading cause of blindness in elderly people, but the pathophysiology of this disease is still largely unknown. We investigated the systemic expression of angiogenesis-regulating growth factors and selected miRNAs known to regulate angiogenesis in A...

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Autores principales: Ulańczyk, Zofia, Sobuś, Anna, Łuczkowska, Karolina, Grabowicz, Aleksandra, Mozolewska-Piotrowska, Katarzyna, Safranow, Krzysztof, Kawa, Miłosz Piotr, Pałucha, Andrzej, Krawczyk, Mariusz, Sikora, Piotr, Matczyńska, Ewa, Machaliński, Bogusław, Machalińska, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887747/
https://www.ncbi.nlm.nih.gov/pubmed/31731799
http://dx.doi.org/10.3390/ijms20225750
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author Ulańczyk, Zofia
Sobuś, Anna
Łuczkowska, Karolina
Grabowicz, Aleksandra
Mozolewska-Piotrowska, Katarzyna
Safranow, Krzysztof
Kawa, Miłosz Piotr
Pałucha, Andrzej
Krawczyk, Mariusz
Sikora, Piotr
Matczyńska, Ewa
Machaliński, Bogusław
Machalińska, Anna
author_facet Ulańczyk, Zofia
Sobuś, Anna
Łuczkowska, Karolina
Grabowicz, Aleksandra
Mozolewska-Piotrowska, Katarzyna
Safranow, Krzysztof
Kawa, Miłosz Piotr
Pałucha, Andrzej
Krawczyk, Mariusz
Sikora, Piotr
Matczyńska, Ewa
Machaliński, Bogusław
Machalińska, Anna
author_sort Ulańczyk, Zofia
collection PubMed
description Age-related macular degeneration (AMD) remains the leading cause of blindness in elderly people, but the pathophysiology of this disease is still largely unknown. We investigated the systemic expression of angiogenesis-regulating growth factors and selected miRNAs known to regulate angiogenesis in AMD patients. We also focused on possible correlations of their expression with the presence of CFH Y402H or ARMS A69S risk variants. A total of 354 AMD patients and 121 controls were enrolled in this study. The levels of angiogenesis-regulating factors were analyzed in plasma samples using Luminex technology. The expression of selected miRNAs was analyzed in peripheral blood plasma using real-time qPCR. The genetic analysis was performed with an Illumina NextSeq500 system. AMD was an independent factor associated with lower levels of angiogenin (β = −0.29, p < 0.001), endostatin (β = −0.18, p < 0.001), FGF-basic (β = −0.18, p < 0.001), PlGF (β = −0.24, p < 0.001), miRNA-21-3p (β = −0.13, p = 0.01) and miRNA-155-5p (β = −0.16, p = 0.002); and with higher levels of FGF-acidic (β = 0.11, p = 0.03), miRNA-23a-3p (β = 0.17, p < 0.001), miRNA-126-5p (β = 0.13, p = 0.009), miRNA-16-5p (β = 0.40, p < 0.001), miRNA-17-3p (β = 0.13, p = 0.01), miRNA-17-5p (β = 0.17, p < 0.001), miRNA-223-3p (β = 0.15, p = 0.004), and miRNA-93 (β = 0.11, p = 0.04). The expression of analyzed miRNA molecules significantly correlated with the levels of tested angiogenesis-regulating factors and clinical parameters in AMD patients, whereas such correlations were not observed in controls. We also found an association between the CFH Y402H polymorphism and miRNA profiles, whereby TT homozygotes showed evidently higher expression of miRNA-16-5p than CC homozygotes or TC heterozygotes (p = 0.0007). Our results suggest that the balance between systemic pro- and anti-angiogenic factors and miRNAs is vital in multifactorial AMD pathogenesis.
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spelling pubmed-68877472019-12-09 Associations of MicroRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism—An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration Ulańczyk, Zofia Sobuś, Anna Łuczkowska, Karolina Grabowicz, Aleksandra Mozolewska-Piotrowska, Katarzyna Safranow, Krzysztof Kawa, Miłosz Piotr Pałucha, Andrzej Krawczyk, Mariusz Sikora, Piotr Matczyńska, Ewa Machaliński, Bogusław Machalińska, Anna Int J Mol Sci Article Age-related macular degeneration (AMD) remains the leading cause of blindness in elderly people, but the pathophysiology of this disease is still largely unknown. We investigated the systemic expression of angiogenesis-regulating growth factors and selected miRNAs known to regulate angiogenesis in AMD patients. We also focused on possible correlations of their expression with the presence of CFH Y402H or ARMS A69S risk variants. A total of 354 AMD patients and 121 controls were enrolled in this study. The levels of angiogenesis-regulating factors were analyzed in plasma samples using Luminex technology. The expression of selected miRNAs was analyzed in peripheral blood plasma using real-time qPCR. The genetic analysis was performed with an Illumina NextSeq500 system. AMD was an independent factor associated with lower levels of angiogenin (β = −0.29, p < 0.001), endostatin (β = −0.18, p < 0.001), FGF-basic (β = −0.18, p < 0.001), PlGF (β = −0.24, p < 0.001), miRNA-21-3p (β = −0.13, p = 0.01) and miRNA-155-5p (β = −0.16, p = 0.002); and with higher levels of FGF-acidic (β = 0.11, p = 0.03), miRNA-23a-3p (β = 0.17, p < 0.001), miRNA-126-5p (β = 0.13, p = 0.009), miRNA-16-5p (β = 0.40, p < 0.001), miRNA-17-3p (β = 0.13, p = 0.01), miRNA-17-5p (β = 0.17, p < 0.001), miRNA-223-3p (β = 0.15, p = 0.004), and miRNA-93 (β = 0.11, p = 0.04). The expression of analyzed miRNA molecules significantly correlated with the levels of tested angiogenesis-regulating factors and clinical parameters in AMD patients, whereas such correlations were not observed in controls. We also found an association between the CFH Y402H polymorphism and miRNA profiles, whereby TT homozygotes showed evidently higher expression of miRNA-16-5p than CC homozygotes or TC heterozygotes (p = 0.0007). Our results suggest that the balance between systemic pro- and anti-angiogenic factors and miRNAs is vital in multifactorial AMD pathogenesis. MDPI 2019-11-15 /pmc/articles/PMC6887747/ /pubmed/31731799 http://dx.doi.org/10.3390/ijms20225750 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ulańczyk, Zofia
Sobuś, Anna
Łuczkowska, Karolina
Grabowicz, Aleksandra
Mozolewska-Piotrowska, Katarzyna
Safranow, Krzysztof
Kawa, Miłosz Piotr
Pałucha, Andrzej
Krawczyk, Mariusz
Sikora, Piotr
Matczyńska, Ewa
Machaliński, Bogusław
Machalińska, Anna
Associations of MicroRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism—An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration
title Associations of MicroRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism—An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration
title_full Associations of MicroRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism—An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration
title_fullStr Associations of MicroRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism—An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration
title_full_unstemmed Associations of MicroRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism—An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration
title_short Associations of MicroRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism—An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration
title_sort associations of micrornas, angiogenesis-regulating factors and cfh y402h polymorphism—an attempt to search for systemic biomarkers in age-related macular degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887747/
https://www.ncbi.nlm.nih.gov/pubmed/31731799
http://dx.doi.org/10.3390/ijms20225750
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