Review
Biochemistry & Molecular Biology
Keiichi Asano, Anna Cantalupo, Lauriane Sedes, Francesco Ramirez
Summary: This article describes a series of studies on Marfan syndrome that have implicated endothelial dysfunction and improper angiotensin II and TGF beta signaling in driving thoracic aortic disease in Marfan syndrome mice. These investigations have influenced the conceptualization of possible new therapies to slow down or even halt aneurysm progression in this relatively common connective tissue disorder.
Article
Cardiac & Cardiovascular Systems
Maxim Avanesov, Julius Matthias Weinrich, Martin Sinn, Alexander Lenz, Felicia von Duering, Johannes Salamon, Frank-Oliver Henes, Bjoern Peter Schoennagel, Gerhard Adam, Yskert von Kodolitsch, Peter Bannas
Summary: This study compared aortic measurements at 1.5T and 3T using non-contrast MRA in Marfan patients. The results showed higher interobserver agreement in pre-surgical patients at 3T, while worse image quality and artifacts were observed in post-surgical patients at 3T. Different magnetic field strengths are recommended for monitoring aortic growth in pre- and post-surgical Marfan patients.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Angela Lopez-Sainz, Laia Mila, Jose Rodriguez-Palomares, Javier Limeres, Chiara Granato, Lucia La Mura, Ana Sabate, Andrea Guala, Laura Gutierrez, Laura Galian-Gay, Augusto Sao-Aviles, Sergi Bellmunt, Rafael Rodriguez, Hug Cuellar-Calabria, Albert Roque, Ignacio Ferreira-Gonzalez, Artur Evangelista, Gisela Teixido-Tura
Summary: This study revealed that aortic branch aneurysms are present in approximately one-quarter of patients with MFS, are associated with patient age and aortic dilation, and independently predict the need for aortic surgery.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Felix Sebastian Nettersheim, Julian Lemties, Simon Braumann, Simon Geissen, Senai Bokredenghel, Richard Nies, Alexander Hof, Holger Winkels, Bruce A. Freeman, Anna Klinke, Volker Rudolph, Stephan Baldus, Dennis Mehrkens, Martin Mollenhauer, Matti Adam
Summary: This study found that Nitro-oleic acid can attenuate the progression of aortic dilation in Marfan syndrome by modulating multiple disease-mediating pathways.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Caroline Toolan, Shwe Oo, Matthew Shaw, Mark Field, Manoj Kuduvalli, Deborah Harrington, Omar Nawaytou
Summary: Significant progress has been made in the surgical management of aortic complications of Marfan syndrome (MFS) over the past five decades. However, the varying phenotypic expression complicates the anticipation of future aortic events, highlighting the need for targeted operative techniques and surveillance.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2022)
Review
Biochemistry & Molecular Biology
Charlotte Xue Dong, Cassandra Malecki, Elizabeth Robertson, Brett Hambly, Richmond Jeremy
Summary: Thoracic aortic disease affects all ages, with a majority of cases having a genetic cause. Surgical intervention is currently the main treatment option. The mechanism of thoracic aneurysm is less understood compared to abdominal aortic aneurysm. This paper examines key cell signaling systems and explores potential novel therapeutic approaches for thoracic aortic aneurysm.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Christopher Lau, Giovanni Soletti, Jonathan W. Weinsaft, Mohamed Rahouma, Talal Al Zghari, Roberto Perezgrovas Olaria, Lamia Harik, Mohammad Yaghmour, Arnaldo Dimagli, Mario Gaudino, Leonard N. Girardi
Summary: This study compared operative and long-term outcomes between patients with and without Marfan syndrome undergoing thoracoabdominal aortic aneurysm repair. The study found that patients with and without Marfan syndrome had similar operative outcomes despite differing risk profiles.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2023)
Article
Cardiac & Cardiovascular Systems
Anca Remes, Rawa Arif, Maximilian Franz, Andreas Jungmann, Marcin Zaradzki, Thomas Puehler, Markus B. Heckmann, Norbert Frey, Matthias Karck, Klaus Kallenbach, Markus Hecker, Oliver J. Mueller, Andreas H. Wagner
Summary: This study aimed to establish a novel AAV-based strategy for long-term expression of AP-1 neutralizing RNA hairpin in the aorta to prevent aortic elastolysis in a murine model of Marfan syndrome. The results showed that this approach effectively reduced MMP expression and activity, ROS formation, and inflammation in the aortic tissue.
CARDIOVASCULAR RESEARCH
(2021)
Review
Pediatrics
Laura Muino-Mosquera, Julie De Backer
Summary: Genetic aortic diseases are characterized by aortic aneurysms or dissection caused by genetic defects, with Marfan syndrome being a typical example. These diseases often involve abnormalities in heart valves, which require careful monitoring and management and may lead to mortality.
FRONTIERS IN PEDIATRICS
(2021)
Article
Pharmacology & Pharmacy
Sheilabi Seeburun, Shichao Wu, Darshi Hemani, Lucynda Pham, Donghong Ju, Youming Xie, Priyaranjan Kata, Li Li
Summary: This review summarizes the role of elastic fiber fragmentation in the pathogenesis of Marfan syndrome-associated aortic aneurysms and highlights its clinical significance for targeted interventions and potential therapeutic strategies.
VASCULAR PHARMACOLOGY
(2023)
Article
Hematology
Cristina Caescu, Jens Hansen, Brittany Crockett, Wenzhen Xiao, Pauline Arnaud, Bart Spronck, Alan Weinberg, Takeshi Hashimoto, Sae-Il Murtada, Roshan Borkar, James M. Gallo, Guillaume Jondeau, Catherine Boileau, Jay D. Humphrey, John Cijiang He, Ravi Iyengar, Francesco Ramirez
Summary: HIPK2 has been identified as a key determinant in aneurysmal disease, showing potential as a new target for multidrug therapy against thoracic aortic aneurysm and acute aortic dissection. Gene inactivation of Hipk2 has been found to extend survival in MFS mice by slowing aneurysm growth, indicating its significance in disease progression. Additionally, HIPK2 may act through the TGF-beta/Smad3 signaling pathway to mitigate aortic pathologies.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Tristan Ehrlich, Andreas Hagendorff, Karen Abeln, Lennart Froede, Christian Giebels, Hans-Joachim Schaefers
Summary: This study analyzed the type and frequency of concomitant cusp alterations in patients undergoing surgery for aortic root aneurysm. The results show that cusp prolapse is common but often underdiagnosed by 2D TEE.
Article
Radiology, Nuclear Medicine & Medical Imaging
Felicia Wright, Malte Warncke, Martin Sinn, Inka Ristow, Alexander Lenz, Christoph Riedel, Bjoern P. Schoennagel, Shuo Zhang, Michael G. Kaul, Gerhard Adam, Yskert von Kodolitsch, Susanne Sehner, Peter Bannas
Summary: This study compared the accuracy and precision of 3D-Dixon and 2D-SSFP MR imaging for assessing aortic diameter in Marfan patients. The results showed that both respiratory-gated 3D-Dixon and breath-hold 2D-SSFP MR imaging provided accurate and precise measurements of aortic diameter. However, 3D-Dixon imaging had fewer imaging artifacts and the advantage of orthogonal multiplanar reformations of the aortic root, making it recommended for monitoring aortic diameter in Marfan patients.
EUROPEAN RADIOLOGY
(2023)
Article
Medicine, Research & Experimental
Hualong Bai, Peng Sun, Shunbo Wei, Boao Xie, Mingxing Li, Yanhua Xu, Wang Wang, Yuanfeng Liu, Liwei Zhang, Haoliang Wu, Zhiju Wang, Ying Xing, Zhiwei Wang, Jing'an Li
Summary: Intramural delivery of TGF beta 1 hydrogel can effectively decrease aneurysm and pseudoaneurysm formation and progression in both mice and rats, and pig aortas can also be successfully intramurally injected with hydrogel. This technique may be a promising drug delivery method and therapeutic choice to decrease aneurysm and pseudoaneurysm formation and progression in the clinic.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Cardiac & Cardiovascular Systems
Xiaolang Jiang, Bin Chen, Junhao Jiang, Yun Shi, Tao Ma, Weiguo Fu, Zhihui Dong
Summary: This study aimed to evaluate the mid-term outcomes of thoracic endovascular aorta repair (TEVAR) in patients with Marfan syndrome (MFS) and type B aortic dissection (TBAD). A total of 26 MFS patients underwent TEVAR and had a perioperative mortality rate of 0%. The cumulative survival rate at 5 and 10 years was 88.1% and 82.9% respectively. Patients with thrombosed false lumen (FL) had significantly higher survival and freedom from reintervention rates compared to those with patent FL. However, patients with patent FL were at high risk of late death.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2023)
Article
Cell Biology
Karol M. Cordoba, Irantzu Serrano-Mendioroz, Daniel Jerico, Maria Merino, Lei Jiang, Ana Sampedro, Manuel Alegre, Fernando Corrales, Maria J. Garrido, Paolo G. Martini, Jose Luis Lanciego, Jesus Prieto, Pedro Berraondo, Antonio Fontanellas
Summary: The administration of a recombinant protein, rhApoAI-PBGD, is shown to enhance hepatic enzymatic activity and protect against acute attacks of AIP.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Assunta Cirella, Elixabet Bolanos, Claudia Augusta Di Trani, Carlos E. de Andrea, Sandra Sanchez-Gregorio, Inaki Etxeberria, Jose Gonzalez-Gomariz, Irene Olivera, Davide Brocco, Javier Glez-Vaz, Carlos Luri-Rey, Arantza Azpilikueta, Inmaculada Rodriguez, Myriam Fernandez-Sendin, Josune Egea, Inaki Eguren, Miguel F. Sanmamed, Belen Palencia, Alvaro Teijeira, Pedro Berraondo, Ignacio Melero
Summary: IL12 and IL18 combination therapy can enhance antitumor effects. Intratumoral administration of DR-18 construct can avoid systemic toxicity and improve therapeutic efficiency.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Oncology
Claudia Augusta Di Trani, Assunta Cirella, Leire Arrizabalaga, Angela Bella, Myriam Fernandez-Sendin, Joan Salvador Russo-Cabrera, Celia Gomar, Irene Olivera, Elizabeth Bolanos, Jose Gonzalez-Gomariz, Maite Alvarez, Inaki Etxeberria, Belen Palencia, Alvaro Teijeira, Ignacio Melero, Pedro Berraondo, Fernando Aranda
Summary: Previous studies have found that local delivery of tumor antigen-specific CD8(+) T lymphocytes transiently expressing single-chain IL-12 mRNA is highly effective in treating tumors. In this study, intracavitary adoptive T cell therapy was used to treat peritoneal dissemination of B16-OVA and PANC02-OVA tumors, and it was found that intraperitoneal administration of T cells promoted homing to the omentum more effectively than intravenous administration. Transient IL-12 expression resulted in a favorable reprogramming of the tumor immune microenvironment and longer persistence of transferred T lymphocytes, leading to the development of immunity to endogenous antigens after primary tumor eradication.
Article
Cell Biology
Silvia Giannoccaro, Celeste Ferraguto, Valeria Petroni, Coline Marcelly, Xavier Nogues, Victoria Campuzano, Susanna Pietropaolo
Summary: Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomal microdeletion (7q11.23). A mouse model with a complete deletion (CD) of the equivalent mouse locus has been used to study the mechanisms of WBS. In this study, CD mice were characterized during infancy and adolescence, and exhibited reduced body growth, delayed sensory development, altered behaviors and neuroanatomical changes. These findings highlight the importance of early neurobehavioral alterations as biomarkers for WBS and the significance of adolescence in identifying potential therapeutic targets.
Article
Biochemistry & Molecular Biology
Noura Abdalla, Ester Tobias-Baraja, Alejandro Gonzalez, Gloria Garrabou, Gustavo Egea, Victoria Campuzano
Summary: Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by a strong cardiovascular phenotype and a distinct neurocognitive profile. The cardiovascular features of WBS are primarily linked to the hemizygosity of the elastin (ELN) gene, but the phenotypic variability suggests the presence of additional modulators. Mitochondrial dysfunction and dynamics have been implicated as potential modulators, and a WBS complete deletion (CD) model exhibits similar mitochondrial phenotypes as observed in WBS patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Noura Abdalla, Paula Ortiz-Romero, Isaac Rodriguez-Rovira, Luis A. A. Perez-Jurado, Gustavo Egea, Victoria Campuzano
Summary: Williams-Beuren syndrome (WBS) is a rare disorder characterized by cardiovascular manifestations, including supra-valvular aortic stenosis (SVAS). We investigated the effects of curcumin and verapamil treatment on a WBS mouse model and found that only the combined therapy significantly improved cardiovascular parameters by reducing oxidative stress damage and activating the NRF2 pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Toxicology
Maritza Roxana Garcia Garcia, Noelia Casares, Luz Andrea Martinez Perez, Efren Juarez Curiel, Andres Alberto de Jesus Hernandez, Nina Bogdanchikova, Diana Garibo, Ana G. Rodriguez-Hernandez, Alexey Pestryakov, Sandra Castro Gamboa, Luis Felipe Arias Ruiz, Olivia Torres Bugarin, Pedro Berraondo
Summary: This study evaluated the ability of silver nanoparticles (AgNP) to induce immunogenic cell death (ICD) and their anti-cancer effects in vitro and in vivo. The results showed that AgNP had anti-proliferative effects on CT26 and MCA205 cell lines and could release calreticulin. However, immunization with AgNP-treated tumor cell debris failed to induce a protective immune response in vivo. Further research is needed to explore the combination of AgNP with other ICD inducers to enhance their anti-tumor effect in vivo.
JOURNAL OF IMMUNOTOXICOLOGY
(2023)
Article
Oncology
Maite Alvarez, Carmen Molina, Saray Garasa, Maria C. Ochoa, Maria E. Rodriguez-Ruiz, Gabriel Gomis, Assunta Cirella, Irene Olivera, Javier Glez-Vaz, Jose Gonzalez-Gomariz, Carlos luri-Rey, Arantza Azpilikueta, Elixabet Bolanos, Alvaro Teijeira, Pedro Berraondo, Marisol Quintero, Ignacio Melero
Summary: The poly I:C-based viral mimetic BO-112 has been found to effectively reduce tumor metastasis when intratumorally delivered, particularly when combined with systemic anti-PD-1 mAbs. This neoadjuvant immunotherapy approach relies on antigen-specific effector CD8 T cells and cDC1 antigen-presenting cells.
Article
Biochemistry & Molecular Biology
Nuria Puig, Pol Camps-Renom, Arnau Sole, Ana Aguilera-Simon, Elena Jimenez-Xarrie, Alejandro Fernandez-Leon, Mercedes Camacho, Marina Guasch-Jimenez, Rebeca Marin, Joan Marti-Fabregas, Alejandro Martinez-Domeno, Luis Prats-Sanchez, Francesca Casoni, Belen Perez, Francesc Jimenez-Altayo, Jose Luis Sanchez-Quesada, Sonia Benitez
Summary: This study aimed to identify modified LDLs and antioxidant enzymes associated with plaque vulnerability in patients with ischemic stroke and carotid atherosclerosis. Patients showed lower levels of cholesterol and apolipoproteins, as well as lower enzymatic activities of PAF-AH and PON-1 in HDL and higher levels of oxidized LDL and electronegative LDL. The proportion of LDL(-) was independently associated with carotid stenosis, hypoechoic plaque presence, and diffuse neovessels.
Article
Cell Biology
Irene Olivera, Elixabet Bolanos, Jose Gonzalez-Gomariz, Sandra Hervas-Stubbs, Karina V. Marino, Carlos Luri-Rey, Inaki Etxeberria, Assunta Cirella, Josune Egea, Javier Glez-Vaz, Saray Garasa, Maite Alvarez, Inaki Eguren-Santamaria, Sonia Guedan, Miguel F. Sanmamed, Pedro Berraondo, Gabriel A. Rabinovich, Alvaro Teijeira, Ignacio Melero
Summary: Engineering tumor-specific CD8 T cells with IL-12 mRNA enhances their therapeutic potency when delivered intratumorally.
CELL REPORTS MEDICINE
(2023)
Article
Cell Biology
Maria Carmen Ochoa, Sandra Sanchez-Gregorio, Carlos E. de Andrea, Saray Garasa, Maite Alvarez, Irene Olivera, Javier Glez-Vaz, Carlos Luri-Rey, Inaki Etxeberria, Assunta Cirella, Arantza Azpilikueta, Pedro Berraondo, Josepmaria Argemi, Bruno Sangro, Alvaro Teijeira, Ignacio Melero
Summary: Immune checkpoint-inhibitor combinations are the best therapeutic option for advanced hepatocellular carcinoma (HCC) patients, and the efficacy can be further improved by combining recombinant IL-2 or anti-CD137 mAb with anti-CTLA-4 + anti-PD1 mAbs treatment. A multifocal HCC model was developed to test immunotherapies, and the combination of tumor-specific adoptive T cell therapy with aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 regimens showed synergistic efficacy. The combined immunotherapy treatments enhanced T cell infiltration and the intratumoral performance of T lymphocytes.
CELL REPORTS MEDICINE
(2023)
Article
Medicine, Research & Experimental
Alex Peralvarez-Marin, Montse Sole, Judith Serrano, Alice Taddeucci, Belen Perez, Clara Penas, Gemma Manich, Marcel Jimenez, Pilar D'Ocon, Francesc Jimenez-Altayo
Summary: This study provides the first evidence that TRPV2 channels may modulate vascular tone by balancing opposing inputs from the endothelium and smooth muscle, leading to net vasodilation. The amplification of TRPV2 channel-induced activity by NO emphasizes the pathophysiological relevance of these findings.