Review
Biochemistry & Molecular Biology
Lucia Beltran-Camacho, Marta Rojas-Torres, Ma Carmen Duran-Ruiz
Summary: Critical limb ischemia is the most severe form of peripheral arterial disease, commonly caused by atherosclerosis leading to progressive blockage of arterial vessels. For patients not suitable for surgical intervention, angiogenic cell therapy has emerged as a promising alternative, showing potential for enhancing revascularization by promoting vessel formation and blood flow recovery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Zeen Aref, Paul H. A. Quax
Summary: Neovascularization plays a crucial role in restoring blood flow after ischemia in peripheral arterial disease, with both angiogenesis and arteriogenesis contributing to functional improvements. However, distinguishing the specific contributions of each process can be challenging. Through the in vivo Matrigel plug assay in genetic deficient mice, we were able to evaluate the effects of various gene deficiencies on angiogenesis, providing insights into the role of different genes in this process. Our study suggests that the in vivo Matrigel plug assay may be superior to the murine hind limb ischemia model in evaluating the angiogenic response post ischemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Dongxiao Fan, Chenshu Liu, Zeling Guo, Kan Huang, Meixiu Peng, Na Li, Hengli Luo, Tengyao Wang, Zhipeng Cen, Weikang Cai, Lei Gu, Sifan Chen, Zilun Li
Summary: The study demonstrates that resveratrol (RSV) can improve hind limb ischemia in mice by enhancing angiogenesis through modulating phosphorylation and cytoplasmic re-localization of FoxO1. Metabolomics analysis reveals that pathways involved in pyrimidine metabolism, purine metabolism, as well as alanine, aspartate and glutamate metabolism are closely related to the beneficial effects of RSV on ischemic muscle.
Article
Biochemical Research Methods
Cristina Arce Recatala, Mattia Albiero, Massimo Mattia Santoro
Summary: This article presents a protocol for evaluating post-natal angiogenesis in a mouse hind limb ischemia model, which is a useful tool for assessing metabolic and cellular responses. The protocol involves inducing a severe restriction of blood supply to mimic the real-life scenario observed in clinical settings, followed by laser Doppler imaging to compare the post-ischemic responses of different mouse strains in triggering compensatory arteriogenesis.
Article
Pharmacology & Pharmacy
Tao Chen, Bo Ye, Jing Tan, Haifeng Yang, Faming He, Raouf A. Khalil
Summary: Mesenchymal stem cells, especially those expressing CD146, show potential in improving vascularity and muscle function in a rat model of hind-limb ischemia, reducing apoptosis and increasing vascular endothelial growth factor expression.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Aysegul Kucuk, Yucel Polat, Aydan Kilicarslan, Nuran Sungu, Hakan Kartal, Ali Dogan Dursun, Mustafa Arslan
Summary: This study evaluated the effects of irisin in a murine model of hind limb ischemia reperfusion injury. Results showed that irisin can reduce oxidative stress levels and decrease inflammation, demonstrating a protective effect on skeletal muscle in I/R injury.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Engineering, Biomedical
Andrew Sligar, Gretchen Howe, Julia Goldman, Patricia Felli, Almudena Gomez-Hernandez, Eri Takematsu, Austin Veith, Shubh Desai, William J. Riley, Rohan Singeetham, Lei Mei, Gregory Callahan, David Ashirov, Richard Smalling, Aaron B. Baker
Summary: In this study, an injectable therapy using syndecan-4 proteoliposomes and growth factors was tested in a rabbit model of peripheral ischemia. The therapy showed enhancement in vascularity and new blood vessel growth, particularly in the lower limb. It was also found to be stable and non-toxic, indicating its potential as a promising treatment for inducing vascular regeneration in peripheral ischemia.
ACTA BIOMATERIALIA
(2023)
Article
Peripheral Vascular Disease
Margaret Nalugo, Nikolai Harroun, Chenglong Li, Larisa Belaygorod, Clay F. Semenkovich, Mohamed A. Zayed
Summary: A reported increased incidence of lower extremity amputations in individuals with diabetes treated with canagliflozin raises concerns about the drug's potential impact on peripheral tissue recovery following ischemic events. Canagliflozin appears to impede tissue recovery and may affect peripheral limb perfusion, indicating the need for further clinical investigation in diabetic individuals with a history of peripheral artery disease.
Article
Engineering, Biomedical
Corinne W. Curry, Sarah M. Sturgeon, Brian J. O. 'Grady, Alexis Yates, Andrew Kjar, Hayden Paige, Lucas S. Mowery, Ketaki A. Katdare, Riya Patel, Kate Mlouk, Madison R. Stiefbold, Sidney Vafaie-Partin, Atsuyuki Kawabata, Rachel Mckee, Stephanie Moore-Lotridge, Adrienne Hawkes, Jiro Kusunose, Katherine N. Gibson-Corley, Jeffrey Schmeckpeper, Jonathan G. Schoenecker, Charles F. Caskey, Ethan S. Lippmann
Summary: Researchers have found that a gelatin-based hydrogel without growth factors or encapsulated cells can promote arteriogenesis and reduce tissue damage in a model of critical limb ischemia. The hydrogel recruits smooth muscle cells to vessel structures, restoring limb perfusion and maintaining tissue health for up to 14 days in mice.
Article
Surgery
Jian Tong, Yu Zhang, Pan Yu, Jie Liu, XiaoLiang Mei, Jia Meng
Summary: Inhalation of hydrogen gas significantly reduces infarct volume, mitigates morphological injury, and suppresses oxidative stress damage caused by hind limb IR injury. Additionally, hydrogen gas can alleviate ER stress and apoptosis induced by IR, and modulate the JNK signaling pathway to inhibit IR injury.
JOURNAL OF SURGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Panagiotis Theofilis, Georgia Vogiatzi, Evangelos Oikonomou, Maria Gazouli, Gerasimos Siasos, Hector Katifelis, Despoina Perrea, Manolis Vavuranakis, Dimitrios C. Iliopoulos, Costas Tsioufis, Dimitris Tousoulis
Summary: The study revealed that delivery of microRNA-126 improved vascular perfusion in the ischemic hind limb of mice with upregulation of VEGF. Additionally, a significant negative correlation between microRNA-126 and VEGF tissue expression levels was observed in the entire study population.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Kazuhito Tsuzuki, Yuuki Shimizu, Junya Suzuki, Zhongyue Pu, Shukuro Yamaguchi, Yusuke Fujikawa, Katsuhiro Kato, Koji Ohashi, Mikito Takefuji, Yasuko K. Bando, Noriyuki Ouchi, John W. Calvert, Rei Shibata, Toyoaki Murohara
Summary: This study reveals that circadian rhythm disorders can influence angiogenesis and blood perfusion recovery in a mouse model of hind limb ischemia, potentially through regulating factors such as vascular endothelial growth factor and circulating endothelial progenitor cells. Maintaining circadian rhythm plays an important role in angiogenesis.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Medicine, General & Internal
Florian Simon, Mansur Duran, Waseem Garabet, Hubert Schelzig, Michael Jacobs, Alexander Gombert
Summary: A decade ago, gene therapy was seen as a potential treatment for chronic limb-threatening ischemia, but its safety and clinical feasibility are still in question. Gene therapy can be achieved through transduction and transfection methods, but there are risks involved, such as increased neo-vascularization in undesired tissue, malignant transformation and inflammation, and arterial thrombosis. Clinical trials of gene therapy in vascular occlusive disease have shown mixed results, leaving the role of gene therapy unclear.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Physiology
Victor Lamin, Arul M. Mani, Madhu Singh, Ayotunde O. O. Dokun
Summary: This study investigated the infiltration of endothelial progenitor cells (EPCs) and macrophages in a mouse model of hind limb ischemia (HLI). The results showed a gradual increase in the percentage of EPCs, with the highest level reached on day 7 and sustained until day 14. The population of M1-like macrophages also increased and peaked on day 14, while the population of M2-like macrophages surpassed that of M1-like on day 7. Muscle regeneration and capillary density increased, with peak values observed on days 3 and 7, respectively. Near full perfusion recovery was achieved by day 14.
JOURNAL OF VASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Rui D. Alvites, Mariana V. Branquinho, Ana C. Sousa, Federica Zen, Monica Maurina, Stefania Raimondo, Carla Mendonca, Luis Atayde, Stefano Geuna, Artur S. P. Varejao, Ana C. Mauricio
Summary: This study established a sheep model for common peroneal nerve injuries, describing nerve anatomy, functional consequences, surgical protocol, and therapeutic options. Through morphological and stereological studies, optimal access methods and study periods were determined, providing foundational data for future research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Peripheral Vascular Disease
Paola Perrotta, Margreet R. de Vries, Bart Peeters, Pieter-Jan Guns, Guido R. Y. De Meyer, Paul H. A. Quax, Wim Martinet
Summary: The study shows that deletion of the PFKFB3 gene in ECs can significantly reduce the size of vein graft lesions, IP angiogenesis and hemorrhages, without obvious adverse effects or changes in general metabolism. Additionally, RT-PCR results indicate an increased M2 macrophage signature in vein grafts from mice with EC-specific PFKFB3 deletion.
Article
Endocrinology & Metabolism
Joost Brinks, Elon H. C. van Dijk, Szymon M. Kielbasa, Hailiang Mei, Isa van der Veen, Hendrika A. B. Peters, Hetty C. M. Sips, Robbert G. E. Notenboom, Paul H. A. Quax, Camiel J. F. Boon, Onno C. Meijer
Summary: Glucocorticoid receptor plays a predominant role in mediating the response to cortisol in human choroidal endothelial cells (CECs). Interindividual differences are important determinants in the cortisol response of human cultured CECs, while intrinsic sex differences appear to be less pronounced. Target genes such as ZBTB16 show a marked response to cortisol in endothelial cells and may have a potential role in the pathophysiology of CSC and other vascular conditions.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Ophthalmology
J. Brinks, E. H. C. van Dijk, I Klaassen, R. O. Schlingemann, S. M. Kielbasa, E. Emri, P. H. A. Quax, A. A. Bergen, O. C. Meijer, C. J. F. Boon
Summary: The choroid plays a crucial role in maintaining ocular homeostasis and is involved in various chorioretinal diseases. Recent advances in single-cell RNA sequencing have provided valuable insights into the characteristics of choroidal endothelial cells (CECs).
PROGRESS IN RETINAL AND EYE RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Eva van Ingen, Daphne A. L. van den Homberg, M. Leontien van der Bent, Hailiang Mei, Nikolina Papac-Milicevic, Veerle Kremer, Reinier A. Boon, Paul H. A. Quax, Johann Wojta, A. Yael Nossent
Summary: This study aimed to elucidate the function and mechanism of DLK1-DIO3 snoRNAs associated with cardiovascular disease. Through overexpression or inhibition of AF357425 in murine fibroblasts, the researchers found that these snoRNAs regulate pre-mRNA processing and protein expression. Additionally, they identified methylation modifications in integrin pathway genes using RNA-Seq, and observed decreased methylation and expression under SNORD113-6 inhibition in both mouse and human fibroblasts.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Daphne A. L. van den Homberg, Reginald V. C. T. van der Kwast, Paul H. A. Quax, A. Yael Nossent
Summary: N-6-methyladenosine (m6A) is a common post-transcriptional RNA modification that can be dynamically regulated by enzymes. This study investigates the role of m6A methylation in fibroblasts, specifically focusing on vasoactive microRNAs. The research found that hypoxia increases m6A levels in mature microRNAs, and METTL4 is the enzyme responsible for this increase. Additionally, the study reveals that microRNA m6A modification directly affects downstream target mRNA repression. These findings highlight the regulatory potential of microRNA modifications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Letter
Endocrinology & Metabolism
Joost Brinks, Elon H. C. van Dijk, Robbert G. E. Notenboom, Paul H. A. Quax, Camiel J. F. Boon, Onno C. Meijer
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Cardiac & Cardiovascular Systems
Taisiya Bezhaeva, Jacco Karper, Paul H. A. Quax, Margreet R. de Vries
Summary: Activation of Toll like receptors (TLR) plays a crucial role in cardiovascular diseases. TLR accessory molecules have not been fully understood in the cardiovascular system, but understanding their role may have significant implications for manipulating inflammatory responses in cardiovascular diseases.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Medicine, Research & Experimental
Hugo Fernandes, Alessandra Zonnari, Ricardo Abreu, Sezin Aday, Marta Barao, Ines Albino, Miguel Lino, Ana Branco, Catia Seabra, Tania Barata, Ermelindo C. Leal, Jose Guilherme Tralhao, Lino Goncalves, Alwin de Jong, Hendrika A. B. Peters, Margreet R. de Vries, Paula da Costa Martins, Paul H. A. Quax, Lino Ferreira
Summary: The study identified miR-425-5p as a molecule capable of enhancing endothelial cell survival and migration, modulating the PTEN/PI3K/AKT pathway to promote cell survival, and successfully delivering it in vivo through modulation of small extracellular vesicles, ultimately enhancing wound healing.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Cardiac & Cardiovascular Systems
Suzanne L. Laboyrie, Margreet R. de Vries, Alwin de Jong, Hetty C. de Boer, Reshma A. Lalai, Laisel Martinez, Roberto Vazquez-Padron, Joris Rotmans
Summary: This study investigated the effects of von Willebrand Factor (vWF) on arteriovenous fistula (AVF) maturation. The results showed that vWF deficiency reduces vascular smooth muscle cell (VSMC) proliferation and macrophage infiltration, leading to decreased outward remodeling and intimal hyperplasia in AVFs. Furthermore, increased vWF expression was observed in matured AVFs, which correlated with outward remodeling. These findings suggest that vWF plays an important role in AVF maturation.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Biochemistry & Molecular Biology
Vincent Q. Sier, Alwin de Jong, Paul H. A. Quax, Margreet R. de Vries
Summary: This study quantified vascular remodeling and blood flow changes in murine VG and AVF models using ultra-high-frequency ultrasound imaging. Results showed significantly increased wall volume and outward remodeling in Apoe3*Leiden mice, whereas wall volume remained constant in C57BL/ 6J mice. For VGs, there was a decrease in proximal pulsatility index, resistive index, and peak systolic velocity, and an increase in maximum acceleration in the distal region. Distinct flow patterns were observed in AVFs compared to control carotid arteries.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Fabiana Baganha, Thijs J. Sluiter, Rob C. M. de Jong, Louise A. van Alst, Hendrika A. B. Peters, J. Wouter Jukema, Mirela Delibegovic, Knut Pettersson, Paul H. A. Quax, Margreet R. de Vries
Summary: Based on the study in mice VG, PC-mAb can effectively inhibit the formation of atherosclerotic lesions by reducing IPA and IPH, decreasing neovessel density and macrophages influx, and increasing neovessel maturation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Melody Chemaly, David Marlevi, Maria-Jesus Iglesias, Mariette Lengquist, Malin Kronqvist, Daniel Bos, Dianne H. K. van Dam-Nolen, Anja van der Kolk, Jeroen Hendrikse, Mohamed Kassem, Ljubica Matic, Jacob Odeberg, Margreet R. de Vries, M. Eline Kooi, Ulf Hedin
Summary: This study explored the biomarker potential of plasma BLVRB, finding that it is associated with intraplaque hemorrhage (IPH) in carotid plaques and the risk of recurrent ischemic stroke. Additionally, the study demonstrated that plasma BLVRB levels can be used to monitor the efficacy of pharmacotherapy targeting IPH. These findings suggest that plasma BLVRB may serve as a biomarker for atherosclerotic plaque instability.
Review
Biochemistry & Molecular Biology
Suzanne L. L. Laboyrie, Margreet R. R. de Vries, Roel Bijkerk, Joris I. I. Rotmans
Summary: Vascular access is crucial for patients undergoing hemodialysis, and arteriovenous fistula (AVF) is the preferred choice due to its high-flow conduit. AVF maturation, the process of increasing luminal diameter and vessel wall of the venous outflow tract, is important for successful AVF use. The role of extracellular matrix (ECM) in AVF maturation is still unclear. The ECM provides structural support, communicates with vascular cells, and is involved in multiple processes that regulate AVF maturation. This review explores the composition of arterial and venous ECM, ECM remodelling post-AVF surgery, and current interventions to improve AVF maturation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
