Article
Cardiac & Cardiovascular Systems
Lisa E. Dorn, William Lawrence, Jennifer M. Petrosino, Xianyao Xu, Thomas J. Hund, Bryan A. Whitson, Matthew S. Stratton, Paul M. L. Janssen, Peter J. Mohler, Anders Schlosser, Grith L. Sorensen, Federica Accornero
Summary: This study identified a novel role for nonmyocyte-derived MFAP4 in cardiac remodeling, playing a crucial role in cardiac adaptation to stress. Lack of MFAP4 resulted in increased cardiac hypertrophy, worsened cardiac function, and dysregulated G protein-coupled receptor and integrin signaling in the heart.
CIRCULATION RESEARCH
(2021)
Article
Peripheral Vascular Disease
Katarzyna Hackert, Susanne Homann, Shakila Mir, Arne Beran, Simone Gorressen, Florian Funk, Jens W. Fischer, Maria Grandoch, Joachim P. Schmitt
Summary: 4-MU can attenuate inflammation and extracellular matrix remodeling in pressure-overloaded myocardium by reducing both resident and invading cardiac macrophages, leading to reduced myocardial fibrosis. Additionally, 4-MU also reduces left ventricular hypertrophy and increases cardiac output after TAC surgery.
Article
Cell Biology
Satoshi Kawaguchi, Bruno Moukette, Marisa N. Sepulveda, Taiki Hayasaka, Tatsuya Aonuma, Angela K. Haskell, Jessica Mah, Suthat Liangpunsakul, Yaoliang Tang, Simon J. Conway, Il-man Kim
Summary: miR-150 is downregulated during heart failure and correlates with patient outcomes. It protects against myocardial infarction by reducing cardiomyocyte apoptosis and targets small proline-rich protein 1a. Knockdown of SPrr1a improves cardiac dysfunction and fibrosis post-MI.
CELL DEATH & DISEASE
(2023)
Article
Medicine, Research & Experimental
Pearl Quijada, Shuin Park, Peng Zhao, Kamal S. S. Kolluri, David Wong, Kevin D. Shih, Kai Fang, Arash Pezhouman, Lingjun Wang, Ali Daraei, Matthew D. Tran, Elle M. Rathbun, Kimberly N. Burgos Villar, Maria L. Garcia-Hernandez, Thanh T. D. Pham, Charles J. Lowenstein, M. Luisa Iruela-Arispe, S. Thomas Carmichael, Eric M. Small, Reza Ardehali
Summary: The role of pericytes in ischemia-induced remodeling in the heart was investigated. Pericytes migrated to the injury site and expressed profibrotic genes, leading to increased vessel leakage after myocardial infarction. Single-cell RNA-Seq analysis revealed the induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-beta signaling. Targeting TGF-beta receptor 1 in pericytes reduced fibrosis and improved cardiac function after MI, while genetic ablation of pericytes resulted in excessive vascular permeability, declined cardiac function, and increased mortality. These findings highlight the importance of pericytes in controlling vascular homeostasis and the fibrotic response to acute ischemic injury, providing insights for novel therapeutic approaches.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Cardiac & Cardiovascular Systems
Menglong Wang, Mengmeng Zhao, Junping Yu, Yao Xu, Jishou Zhang, Jianfang Liu, Zihui Zheng, Jing Ye, Zhen Wang, Di Ye, Yongqi Feng, Shuwan Xu, Wei Pan, Cheng Wei, Jun Wan
Summary: This study investigated the effects of the selective NLRP3 inhibitor MCC950 on heart failure (HF) induced by pressure overload in obese mice and its metabolic mechanism. The results showed that MCC950 improved cardiac hypertrophy, fibrosis, and inflammation in obese mice. It also promoted M2 macrophage infiltration and regulated fatty acid and glucose uptake and utilization. Additionally, MCC950 affected the phosphorylation of AKT and AMPK in obese mice with HF.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Jin Li, Ane M. Salvador, Guoping Li, Nedyalka Valkov, Olivia Ziegler, Ashish Yeri, Chun Yang Xiao, Bessie Meechoovet, Eric Alsop, Rodosthenis S. Rodosthenous, Piyusha Kundu, Tianxiao Huan, Daniel Levy, John Tigges, Alexander R. Pico, Ionita Ghiran, Michael G. Silverman, Xiangmin Meng, Robert Kitchen, Jiahong Xu, Kendall Van Keuren-Jensen, Ravi Shah, Junjie Xiao, Saumya Das
Summary: miR-30d can improve cardiac function and reduce fibrosis by targeting MAP4K4 and integrin alpha 5, showing a protective effect in ischemic heart failure. The communication of extracellular vesicle-contained miRNAs may provide a novel therapeutic target in heart failure treatment.
CIRCULATION RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Javier Barallobre-Barreiro, Tamas Radovits, Marika Fava, Ursula Mayr, Wen-Yu Lin, Elizaveta Ermolaeva, Diego Martinez-Lopez, Eric L. Lindberg, Elisa Duregotti, Laszlo Daroczi, Maria Hasman, Lukas E. Schmidt, Bhawana Singh, Ruifang Lu, Ferheen Baig, Aleksandra Malgorzata Siedlar, Friederike Cuello, Norman Catibog, Konstantinos Theofilatos, Ajay M. Shah, Maria G. Crespo-Leiro, Nieves Domenech, Norbert Hubner, Bela Merkely, Manuel Mayr
Summary: The study identified ADAMTS5 protease as critical for versican degradation in the heart and found that versican accumulation is associated with impaired cardiac function in heart failure patients and animal models. Versikine, an ADAMTS-specific cleavage product, accumulated in ischemic heart failure patients and following cardiac ischemia/reperfusion injury in animal models. The use of beta-blockers in heart failure patients was associated with a reduction in ECM deposition, particularly in the levels of versican, indicating a potential beneficial effect on cardiac chondroitin sulfate proteoglycan content.
Article
Biochemistry & Molecular Biology
Annakaisa Tirronen, Nicholas L. Downes, Jenni Huusko, Johanna P. Laakkonen, Tomi Tuomainen, Pasi Tavi, Marja Hedman, Seppo Yla-Herttuala
Summary: Experimental studies have shown that VEGFR-1 signaling plays a crucial role in cardiac remodeling during pressure overload, and its deficiency leads to changes in LVH and increased risk of sudden death.
Article
Chemistry, Multidisciplinary
Fang-fang Ren, Lin Zhao, Xian-yun Jiang, Jing-jing Zhang, Jia-min Gou, Xiao-yu Yu, Shu-jin Wu, Lei Li
Summary: Apoptosis, or programmed cell death, plays a critical role in the development of heart failure. Sphingosylphosphorylcholine (SPC), a bioactive sphingolipid, has been shown to inhibit apoptosis in myofibroblasts, non-muscle cells in the heart. In this study, the researchers investigated the role of the SPC receptor, calmodulin (CaM), in cardiomyocyte apoptosis and the associated signaling pathways. They found that SPC administration improved survival rate, cardiac hypertrophy, and cardiac fibrosis in mice with pressure overload-induced heart failure. In cardiomyocytes, SPC treatment inhibited cardiomyocyte hypertrophy, fibroblast-to-myofibroblast transition, and cell apoptosis. This was accompanied by reduced levels of pro-apoptotic proteins and phosphorylation of CaM, JNK, and p38, as well as increased levels of a cardiomyocyte-protective protein. The protective effect of SPC was annulled by a compound that increased CaM function. The researchers also demonstrated that SPC-mediated inhibition of cardiomyocyte apoptosis involved the regulation of p38 and JNK phosphorylation, which was downstream of CaM. These findings provide new evidence for SPC regulation of cardiomyocyte apoptosis and suggest it as a potential therapeutic target for cardiac remodeling following stress overload.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Cardiac & Cardiovascular Systems
Nikolaos G. Frangogiannis
Summary: Myocardial fibrosis, characterized by the expansion of cardiac interstitium through deposition of extracellular matrix proteins, is a common pathophysiologic feature in various myocardial conditions. Activated fibroblasts and myofibroblasts play a central role in cardiac fibrosis, producing matrix proteins and triggering fibrogenic signalling cascades in response to stress. Immune cells, vascular cells, and cardiomyocytes can also contribute to fibrosis, while fibrotic changes may disrupt cardiac function and play a role in arrhythmogenesis.
CARDIOVASCULAR RESEARCH
(2021)
Review
Biology
Christopher J. Gilbert, Jacob Z. Longenecker, Federica Accornero
Summary: Understanding how cardiac cells respond to external stimuli through the ERK1/2 pathway is crucial for maintaining heart health and responding to stress. The review highlights the complexity of upstream and downstream signals involved in ERK1/2-dependent regulation, particularly focusing on cardiomyocyte hypertrophy as an outcome of ERK1/2 activation regulation in the heart.
Article
Cardiac & Cardiovascular Systems
Jamie Francisco, Jin Guan, Yu Zhang, Yasuki Nakada, Satvik Mareedu, Eunah Sung, Che-Ming Hu, Shinichi Oka, Peiyong Zhai, Junichi Sadoshima, Dominic P. Del Re
Summary: Inflammation is a crucial factor in cardiovascular disease, and Yes-associated protein (YAP) has been found to play a key role in modulating inflammation in ischemic injury. This study investigated the role of YAP in non-ischemic cardiac inflammation. The results showed that YAP activation in myeloid cells contributes to cardiac inflammation and fibrosis during pressure overload stress. Inhibition of YAP may be a potential therapeutic target for non-ischemic heart disease.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Diana Paola Gomez-Mendoza, Ana Carolina Lara-Ribeiro, Thiago Verano-Braga
Summary: Cardiac remodeling involves multifactorial events leading to cellular and structural changes, ultimately resulting in ventricular dysfunction and heart failure. Proteins play a crucial role in orchestrating molecular events that impact heart structure and function through various mechanisms.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2021)
Article
Biology
Robert A. Eder, Maaike van den Boomen, Salva R. Yurista, Yaiel G. Rodriguez-Aviles, Mohammad Rashedul Islam, Yin-Ching Iris Chen, Lena Trager, Jaume Coll-Font, Leo Cheng, Haobo Li, Anthony Rosenzweig, Christiane D. Wrann, Christopher T. Nguyen
Summary: This study reveals that exercise training induces regional remodeling of the heart's microstructural tissue, and the expression of the CITED4 gene is necessary for this process.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elise L. Kessler, Jiong-Wei Wang, Bart Kok, Maike A. Brans, Angelique Nederlof, Leonie van Stuijvenberg, Chenyuan Huang, Aryan Vink, Fatih Arslan, Igor R. Efimov, Carolyn S. P. Lam, Marc A. Vos, Dominique P. de Kleijn, Magda S. C. Fontes, Toon A. B. van Veen
Summary: Deficiency of TLR2 alleviates adverse cardiac remodeling caused by chronic pressure overload, with TLR2 and TLR4 both contributing to this process. The findings provide insights into potential therapeutic targets for preventing or intervening in cardiac diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Ezequiel J. Molina, Matthew F. Sandusky, Dipin Gupta, John P. Gaughan, James B. McClurken, Satoshi Furukawa, Mahender Macha
SCANDINAVIAN CARDIOVASCULAR JOURNAL
(2010)
Article
Medicine, General & Internal
M. R. Mehra, N. Uriel, Y. Naka, J. C. Cleveland, M. Yuzefpolskaya, C. T. Salerno, M. N. Walsh, C. A. Milano, C. B. Patel, S. W. Hutchins, J. Ransom, G. A. Ewald, A. Itoh, N. Y. Raval, S. C. Silvestry, R. Cogswell, R. John, A. Bhimaraj, B. A. Bruckner, B. D. Lowes, J. Y. Um, V. Jeevanandam, G. Sayer, A. A. Mangi, E. J. Molina, F. Sheikh, K. Aaronson, F. D. Pagani, W. G. Cotts, A. J. Tatooles, A. Babu, D. Chomsky, J. N. Katz, P. B. Tessmann, D. Dean, A. Krishnamoorthy, J. Chuang, I. Topuria, P. Sood, D. J. Goldstein
NEW ENGLAND JOURNAL OF MEDICINE
(2019)
Article
Cardiac & Cardiovascular Systems
Nir Uriel, Valluvan Jeevanandam, Teruhiko Imamura, David Onsager, Tae Song, Takeyoshi Ota, Colleen Juricek, Pamela Combs, Thomas Lammy, Sonna Patel-Raman, Joshua R. Woolley, Gabriel Sayer, Carmelo Milano, Jacob Schroder, Ezequiel Molina, Jonathan Grinstein, Erik Suarez, Jerry D. Estep, Sanjeev Aggarwal, Scott Silvestry, Nirav Raval
CIRCULATION-HEART FAILURE
(2020)
Article
Cardiac & Cardiovascular Systems
Benjamin B. Kenigsberg, David T. Majure, Farooq H. Sheikh, Nana Afari-Armah, Maria Rodrigo, Mark Hofmeyer, Ezequiel J. Molina, Zuyue Wang, Steven Boyce, Samer S. Najjar, Selma F. Mohammed
JOURNAL OF CARDIAC FAILURE
(2020)
Article
Cardiac & Cardiovascular Systems
Caitlin J. Cain, Huzaifa Ahmad, Ezequiel J. Molina
JOURNAL OF CARDIAC SURGERY
(2020)
Letter
Radiology, Nuclear Medicine & Medical Imaging
Nathan E. Frenk, Nora E. Tabori, Ezequiel J. Molina, Saher S. Sabri
JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
(2020)
Article
Cardiac & Cardiovascular Systems
Muhtadi Alnababteh, Muhammad D. Hashmi, Karthik Vedantam, Rajus Chopra, Akshay Kohli, Fatima Hayat, Eric Kriner, Ezequiel Molina, Alexandra Pratt, Emil Oweis, Akram M. Zaaqoq
Summary: ECMO is a helpful intervention for COVID-19 associated pneumonia when optimal mechanical ventilation is not effective. Biomarkers like D-dimer, LDH, and troponin could be useful in predicting clinical prognosis in these patients. The study found that ECMO patients had longer mechanical ventilation hours and ICU length of stay compared to MV patients.
Article
Cardiac & Cardiovascular Systems
Ezequiel J. Molina, Palak Shah, Michael S. Kiernan, William K. Cornwell, Hannah Copeland, Koji Takeda, Felix G. Fernandez, Vinay Badhwar, Robert H. Habib, Jeffrey P. Jacobs, Devin Koehl, James K. Kirklin, Francis D. Pagani, Jennifer A. Cowger
Summary: The STS-Intermacs 2020 Annual Report analyzed data from 25,551 patients who underwent LVAD implantation between 2010 and 2019, revealing an increase in African American patients and a higher proportion bridged to durable LVAD with temporary mechanical support devices. The report also showed improvements in 1- and 2-year survival rates in the most recent era compared to the previous era, with major bleeding and infection remaining as leading adverse events.
ANNALS OF THORACIC SURGERY
(2021)
Article
Cardiac & Cardiovascular Systems
Jonathan Grinstein, Ezequiel J. Molina, Farooq H. Sheikh
Summary: This paragraph describes a rare case of successful implantation of a HeartMate 3 left ventricular assist device in a patient with active heparin-induced thrombocytopenia with thrombosis. The patient underwent preoperative plasmapheresis followed by intraoperative prostacyclin administration.
INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY
(2021)
Article
Engineering, Biomedical
Ezequiel J. Molina, Sara Ahmed, Amiti Jain, Phillip H. Lam, Sriram Rao, Michael Hockstein, Ajay Kadakkal, Mark Hofmeyer, Maria E. Rodrigo, Samer S. Najjar, Farooq H. Sheikh
Summary: This study investigated clinical outcomes in patients with small body size following HM3 LVAD implantation, showing comparable survival and incidence of adverse events between small and large BSA groups, with lower pump speed and flow in the small BSA group, as well as no cases of confirmed pump thrombosis.
Article
Engineering, Biomedical
Manavotam Singh, Anirudh Rao, Sara Ahmed, Ezequiel Molina, Farooq H. Sheikh, Hunter Groninger
Summary: A retrospective study on patients who died following LVAD deactivation found that implant strategy was not associated with clinical trajectory leading to end-of-life, but DT patients received DNR orders earlier and had shorter survival post-deactivation compared with BT patients.
Article
Cardiac & Cardiovascular Systems
Ezequiel Molina, Amiti Jain, Sara Ahmed, Phillip Lam, Sriram Rao, Michael Hockstein, Ajay Kadakkal, Mark Hofmeyer, Maria Rodrigo, JiLing Chou, Samer Najjar, Farooq Sheikh
Summary: This study found that smaller preoperative left ventricular end-diastolic dimension (LVEDD) (<=59 mm) in patients receiving a centrifugal-flow LVAD was associated with lower survival and higher incidence of adverse outcomes.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2022)
Article
Cardiac & Cardiovascular Systems
Mohit Pahuja, Shruti Mony, Oluwole Adegbala, Muhammad Adil Sheikh, Jason P. Wermers, Omar Chehab, Ahmed Pasha, Ananya Das, Luis Afonso, Ezequiel J. Molina, Farooq H. Sheikh, Itsik Ben-Dor, Samer S. Najjar, Patrick Brady, Ron Waksman
Summary: This study analyzed the occurrence of gastrointestinal bleeding (GIB) in patients with percutaneous mechanical circulatory support (pMCS) devices and identified risk factors associated with GIB. The incidence of GIB increased over the past decade, and patients with GIB had higher in-hospital mortality, longer length of stay, and higher hospitalization costs. Risk factors for GIB included small bowel and colonic ischemia, colon cancer, diverticulosis, chronic liver disease, and peptic ulcer disease.
AMERICAN JOURNAL OF CARDIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Ezequiel J. Molina, Steven W. Boyce
SEMINARS IN THORACIC AND CARDIOVASCULAR SURGERY
(2013)
Article
Biochemistry & Molecular Biology
E. J. Molina, D. Gupta, J. Palma, J. P. Gaughan, M. Macha
