Review
Cardiac & Cardiovascular Systems
Flavio Giuseppe Biccire, Laura Gatto, Ylenia La Porta, Pasquale Pignatelli, Francesco Prati, Daniele Pastori
Summary: The clinical evidence strongly supports the efficacy of lipid lowering therapy in patients with coronary artery disease (CAD). However, the effects of these therapies on plaque composition and stability are still unclear. Intracoronary imaging (ICI) technologies are being used as a complement to conventional angiography to characterize plaque morphology and detect high-risk plaque features. Current studies show that pharmacological treatment can slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved. The introduction of high-intensity lipid lowering therapy has resulted in greater clinical benefit, but the atheroma regression shown in imaging trials appears more modest compared to the magnitude of clinical benefit.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Roxana Mihaela Chiorescu, Mihaela Mocan, Andreea Ioana Inceu, Andreea Paula Buda, Dan Blendea, Sonia Irina Vlaicu
Summary: Atherosclerosis and its clinical manifestations are the leading cause of death worldwide, mainly due to the rupture of vulnerable plaques and subsequent thrombosis. Traditional imaging methods are unreliable in predicting the risk of rupture, while intravascular imaging is an effective technique. This review summarizes the current literature on biomarkers for diagnosing vulnerable plaques, providing a foundation for risk stratification and treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Prakriti Gaba, Bernard J. Gersh, James Muller, Jagat Narula, Gregg W. Stone
Summary: This article discusses the features of vulnerable plaques in coronary arteries, as well as the non-invasive and invasive diagnostic methods used to characterize them. It also explores the potential prognostic value of identifying vulnerable plaques and the future research needed to explore intensified pharmacological and focal treatments for these plaques.
NATURE REVIEWS CARDIOLOGY
(2023)
Review
Radiology, Nuclear Medicine & Medical Imaging
Takehiro Nakahara, H. William Strauss, Jagat Narula, Mahahiro Jinzaki
Summary: The progression of atherosclerotic plaques is driven by inflammation. Invasive and noninvasive imaging techniques have been developed to identify and characterize vulnerable plaques, which are more likely to rupture and cause clinical events. These imaging techniques identify vessels with focal subendothelial collections of inflammatory cells, lipid/fatty acid deposition, hypoxic regions, expression of angiogenesis factors, protease activation, intravascular thrombus and hemorrhage, apoptosis, and microcalcification. This review provides an overview of atherosclerotic plaque progression and discusses tracers that can visualize specific molecules associated with plaque vulnerability.
SEMINARS IN NUCLEAR MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Xueyu Wang, Yahong Fu, Zulong Xie, Muhua Cao, Wenbo Qu, Xiangwen Xi, Shan Zhong, Minghui Piao, Xiang Peng, Ying Jia, Lingbo Meng, Jinwei Tian
Summary: The study utilized Fbn1(C1039G+/-)LDLR(-/-) mice as a model for atherosclerotic vulnerable plaques, showing that these mice exhibited numerous features of human advanced atherosclerotic unstable plaques after being fed a high-fat diet. This novel model provides insights into the pathological and physiological mechanisms of advanced atherosclerotic unstable plaques.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Engineering, Biomedical
Ming Zhang, Zhongjian Xie, Haijiao Long, Kun Ren, Lianjie Hou, Yu Wang, Xiaodan Xu, Weixing Lei, Zhicheng Yang, Shakeel Ahmed, Han Zhang, Guojun Zhao
Summary: Early delineation of vulnerable atherosclerotic plaques is crucial for prevention and treatment of cardio-cerebral vascular accidents. However, currently available imaging technologies have limitations. Nanoparticle technology is a promising diagnostic strategy for detecting hallmarks of vulnerable plaques.
MATERIALS TODAY BIO
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Rasha Al-Lamee, Gary S. Mintz
Summary: This editorial discusses the predictive role of thin-cap fibroatheroma in diabetic patients with normal fractional flow reserve for clinical events.
EUROPEAN HEART JOURNAL
(2021)
Article
Engineering, Biomedical
Martin Karl Schneider, James Wang, Aris Kare, Shaunak S. Adkar, Darren Salmi, Caitlin F. Bell, Tom Alsaigh, Dhananjay Wagh, John Coller, Aaron Mayer, Sarah J. Snyder, Alexander D. Borowsky, Steven R. Long, Maarten G. Lansberg, Gary K. Steinberg, Jeremy J. Heit, Nicholas J. Leeper, Katherine W. Ferrara
Summary: The study demonstrates the potential of near-infrared auto-photoacoustic (NIRAPA) imaging in detecting plaque components and differentiating stable and vulnerable plaques. The researchers also developed a methodology to combine molecular imaging with spatial transcriptomic and proteomic methods for a more comprehensive understanding of plaque characteristics.
Article
Biochemistry & Molecular Biology
Yue Wang, Xin-yan Liu, Yue Wang, Wen-xin Zhao, Fa-dong Li, Peng-rong Guo, Qian Fan, Xiao-fan Wu
Summary: This study investigated the latent mechanism of NOX2-triggered vulnerable plaque development. The results showed that the NOX2-specific inhibitor GSK2795039 can prevent the formation of vulnerable plaques and enhance macrophage efferocytosis by regulating the MertK/PI3K/AKT pathway.
Review
Pharmacology & Pharmacy
Michele F. Buono, Lotte Slenders, Marian Wesseling, Robin J. G. Hartman, Claudia Monaco, Hester M. den Ruijter, Gerard Pasterkamp, Michal Mokry
Summary: The pathological definition of the vulnerable plaque has provided valuable insights into the mechanisms of myocardial infarction and stroke. New technologies, such as single-cell transcriptomics, offer opportunities for identifying cell-specific determinants and enhancing the understanding of atherosclerotic diseases. The evolving sequencing technologies have identified candidate genes and molecular mechanisms that may impact the risk of atherosclerotic thrombotic events, posing the challenge of translating these insights into tangible discoveries.
VASCULAR PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Judith J. de Vries, Anouchska S. A. Autar, Dianne H. K. Van Dam-Nolen, Samantha J. Donkel, Mohamed Kassem, Anja G. van der Kolk, Twan J. van Velzen, M. Eline Kooi, Jeroen Hendrikse, Paul J. Nederkoorn, Daniel Bos, Aad van der Lugt, Moniek P. M. de Maat, Heleen M. M. van Beusekom
Summary: This study found a positive correlation between plaque vulnerability and levels of neutrophil extracellular traps (NETs) in patients who had not received statins or antithrombotic medication prior to the index event. Further analysis revealed that this association was mainly driven by intraplaque hemorrhage, lipid-rich necrotic core, and ulceration.
Review
Biology
Maria Emfietzoglou, Michail C. Mavrogiannis, Hector M. Garcia-Garcia, Kimon Stamatelopoulos, Ioannis Kanakakis, Michail I. Papafaklis
Summary: Despite advances in treatment, coronary artery disease (CAD) remains a major cause of illness and death worldwide. Invasive and non-invasive imaging techniques have been used to identify high-risk plaques and the vulnerable state of patients with CAD. However, the predictive value of the invasive-only approach is limited, and a more interdisciplinary approach is needed to identify both the vulnerable plaque and patient. This review summarizes and critically evaluates the modalities used for detecting high-risk plaques in patients with CAD and discusses the challenges of the vulnerable plaque concept.
Article
Public, Environmental & Occupational Health
Michelle C. Odden, Adina Zhang, Neal Jawadekar, Annabel Tan, Andrew E. Moran, M. Maria Glymour, Carol Brayne, Adina Zeki Al Hazzouri, Sebastian Calonico
Summary: Regression discontinuity design (RDD) is a quasi-experimental method used for causal inference. This study aims to estimate the effect of statins on myocardial infarction (MI) using RDD and compare it with other methods. The findings suggest that RDD is superior in replicating the protective effect of statins with MI, although precision is poor.
EUROPEAN JOURNAL OF EPIDEMIOLOGY
(2023)
Review
Cell Biology
Benjamin Bartlett, Herbert P. Ludewick, Silvia Lee, Shipra Verma, Roslyn J. Francis, Girish Dwivedi
Summary: This paper reviews the efficacy of different PET imaging radiotracers in characterizing and assessing the risk of vulnerable plaques in acute coronary syndrome. It also discusses the translational potential of novel radiotracers in animal studies and the challenges encountered in murine PET imaging.
Article
Surgery
Brajesh K. Lal, Amir A. Khan, Vikram S. Kashyap, Matthew T. Chrencik, Ajay Gupta, Alexander H. King, Jigar B. Patel, Janice Martinez-Delcid, Domingo Uceda, Sarasi Desikan, Siddhartha Sikdar, John D. Sorkin, Andrew Buckler
Summary: A predictive model incorporating plaque morphology, patient demographics, and clinical information was developed and validated for predicting major adverse neurologic events (MANE) in patients with carotid atherosclerosis. The model performed better than traditional methods relying solely on the degree of stenosis, highlighting the importance of including multiple factors in risk assessment and patient selection for targeted treatment.
JOURNAL OF VASCULAR SURGERY
(2022)
Article
Cardiac & Cardiovascular Systems
Alberto Cecconi, Jean Paul Vilchez-Tschischke, Jesus Mateo, Javier Sanchez-Gonzalez, Samuel Espana, Rodrigo Fernandez-Jimenez, Beatriz Lopez-Melgar, Leticia Fernandez Friera, Gonzalo J. Lopez-Martin, Valentin Fuster, Jesus Ruiz-Cabello, Borja Ibanez
Summary: The study found that colchicine may stabilize atherosclerotic plaque by reducing inflammatory activity and plaque burden, particularly in animals with high cholesterol levels.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Ariella T. Cohain, William T. Barrington, Daniel M. Jordan, Noam D. Beckmann, Carmen A. Argmann, Sander M. Houten, Alexander W. Charney, Raili Ermel, Katyayani Sukhavasi, Oscar Franzen, Simon Koplev, Carl Whatling, Gillian M. Belbin, Jialiang Yang, Ke Hao, Eimear E. Kenny, Zhidong Tu, Jun Zhu, Li-Ming Gan, Ron Do, Chiara Giannarelli, Jason C. Kovacic, Arno Ruusalepp, Aldons J. Lusis, Johan L. M. Bjorkegren, Eric E. Schadt
Summary: The study identifies a single genetic regulatory module that influences both cholesterol levels and glucose levels, providing a link between cholesterol levels and diabetes.
NATURE COMMUNICATIONS
(2021)
Article
Cardiac & Cardiovascular Systems
Moritz von Scheidt, Yuqi Zhao, Thomas Q. de Aguiar Vallim, Nam Che, Michael Wierer, Marcus M. Seldin, Oscar Franzen, Zeyneb Kurt, Shichao Pang, Dario Bongiovanni, Masayuki Yamamoto, Peter A. Edwards, Arno Ruusalepp, Jason C. Kovacic, Matthias Mann, Johan L. M. Bjorkegren, Aldons J. Lusis, Xia Yang, Heribert Schunkert
Summary: The study identified the transcription factor MAFF as a central regulator of atherosclerosis/CAD-relevant liver network, playing a key role in the expression of LDLR and other genes affecting CAD risk. This finding reveals the important role of MAFF in inflammation, lipid, and lipoprotein metabolism.
Article
Cardiac & Cardiovascular Systems
Robin J. G. Hartman, Katie Owsiany, Lijiang Ma, Simon Koplev, Ke Hao, Lotte Slenders, Mete Civelek, Michal Mokry, Jason C. Kovacic, Gerard Pasterkamp, Gary Owens, Johan L. M. Bjorkegren, Hester M. den Ruijter
Summary: By comparing sex-specific gene regulatory networks (GRNs), clear sex differences in network activity within atherosclerotic tissues were observed. Genes more active in women were associated with mesenchymal cells and endothelial cells, while genes more active in men were associated with the immune system.
Article
Cardiac & Cardiovascular Systems
Joao P. Monteiro, Julie Rodor, Axelle Caudrillier, Jessica P. Scanlon, Ana-Mishel Spiroski, Tatiana Dudnakova, Beatrice Pfluger-Muller, Alena Shmakova, Alex von Kriegsheim, Lin Deng, Richard S. Taylor, John R. Wilson-Kanamori, Shiau-Haln Chen, Kevin Stewart, Adrian Thomson, John D. McClure, Jean Iynikkel, Patrick W. F. Hadoke, Laura Denby, Angela C. Bradshaw, Paola Caruso, Nicholas W. Morrell, Jason C. Kovacic, Igor Ulitsky, Neil C. Henderson, Andrea Caporali, Matthias S. Leisegang, Ralf P. Brandes, Andrew H. Baker, Tijana Mitic
Summary: This study identified a novel lncRNA transcriptional profile associated with EndMT and highlighted the crucial role of MIR503HG loss in EndMT and its relevance to pulmonary hypertension. The findings suggest that MIR503HG may have therapeutic potential in treating EndMT-related conditions such as pulmonary hypertension. Additionally, the study revealed an interaction between MIR503HG and PTBP1, pointing to a potential mechanism by which MIR503HG mediates its effects on EndMT.
CIRCULATION RESEARCH
(2021)
Editorial Material
Cardiac & Cardiovascular Systems
Julien Barc, Jason C. Kovacic
Summary: This commentary discusses the regulatory genomic circuitry of human disease loci using integrative epigenomics, providing a new perspective for understanding the pathogenesis of diseases.
CARDIOVASCULAR RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Diane Fatkin, Hugh Calkins, Perry Elliott, Cynthia A. James, Stacey Peters, Jason C. Kovacic
Summary: Inherited cardiomyopathies are common myocardial disorders with significant morbidity and mortality. Clinical management focuses on treating heart failure and arrhythmias, with precision medicine offering new possibilities tailored to genetic variations, although phenotypic variability suggests involvement of other factors.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Clint L. Miller, Amy R. Kontorovich, Ke Hao, Lijiang Ma, Conrad Iyegbe, Johan L. M. Bjorkegren, Jason C. Kovacic
Summary: Atherosclerosis is the most common vascular disease worldwide, while Mendelian vascular diseases are caused by single genetic changes. These two types of diseases have very different genetic bases, thus requiring different precision medicine approaches for treatment.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Silvia G. Priori, Andrea Mazzanti, Demetrio J. Santiago, Deni Kukavica, Alessandro Trancuccio, Jason C. Kovacic
Summary: This article focuses on the precision medicine opportunities for catecholaminergic polymorphic ventricular tachycardia (CPVT), highlighting that CPVT can manifest as typical or atypical forms with different genetic changes and features, which is crucial for implementing personalized therapeutic approaches.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Christopher Semsarian, Jodie Ingles, Samantha Barratt Ross, Sally L. Dunwoodie, Richard D. Bagnall, Jason C. Kovacic
Summary: Rapid advancements in understanding the genetic basis of cardiovascular diseases have ushered in the era of precision medicine, involving improved diagnostics, family screening, and targeted therapeutics. Future endeavors include polygenic risk scores and genome editing approaches for effective disease treatment.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Alexander Maier, Steve Lin Liao, Thomas Lescure, Philip M. Robson, Naoki Hirata, Samantha Sartori, Navneet Narula, Vittoria Vergani, Georgios Soultanidis, Adam Morgenthau, Jason C. Kovacic, Maria Padilla, Jagat Narula, Adam Jacobi, Zahi A. Fayad, Maria G. Trivieri
Summary: This study found that the uptake of F-18-fluorodeoxyglucose in the pulmonary artery is associated with pulmonary hypertension and its intensity correlates with pulmonary artery pressure.
JACC-CARDIOVASCULAR IMAGING
(2022)
Article
Cardiac & Cardiovascular Systems
Sul Ki Kim, Edwina Wing-Lun, Jaya Chandrasekhar, Aniket Puri, Sonya Burgess, Thomas J. Ford, Jason Kovacic, Robert M. Graham, Peter J. Psaltis, Sarah Zaman
Summary: This study aims to describe the clinical presentation, management, and outcomes of SCAD patients in Australia/New Zealand, as well as to identify predictors of acute deterioration and recurrence. It is a multi-center prospective and historical cohort study that will also pool international data. The study will provide valuable insights into SCAD care and help improve clinical practices.
HEART LUNG AND CIRCULATION
(2022)
Article
Biochemistry & Molecular Biology
Kathryn Wolhuter, Stephanie M. Y. Kong, Christopher P. Stanley, Jason C. Kovacic
Summary: Coronary artery disease (CAD) is commonly treated using percutaneous coronary interventions (PCI), but PCI with stent placement can damage the endothelium. This review examines the role of endothelial-derived oxidants and the effects of altered redox signaling on endothelial dysfunction (ED). It also explores the impact of PCI and stent placement on oxidant production and discusses how recent advances aim to mitigate oxidative damage and improve outcomes.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Cardiac & Cardiovascular Systems
Marina Wassif, Phillip Lo, Paul Satouris, Lucinda Swan, Daniel Tardo, Jason C. Kovacic, David Muller, Kavitha Muthiah, Eugene Kotlyar, Nicole K. Bart
Summary: This retrospective analysis examined patients with suspected COVID-19 vaccine-related myocarditis and pericarditis presenting at St Vincent's Hospital in Sydney, Australia. The results showed that the average age of onset in the vaccine group was 3369.0 years, and the most common symptom was chest pain. 80% of patients had abnormal electrocardiogram findings, and 50% had cardiac monitoring for more than 24 hours. Cardiac complications were rare, mild, and self-limiting, with a good response to oral anti-inflammatories.
HEART LUNG AND CIRCULATION
(2023)
Article
Medicine, Research & Experimental
Laura Lecce, Yang Xu, Bhargavi V'Gangula, Nirupama Chandel, Venu Pothula, Axelle Caudrillier, Maria Paola Santini, Valentina D'Escamard, Delaine K. Ceholski, Przemek A. Gorski, Lijiang Ma, Simon Koplev, Martin Maeng Bjorklund, Johan L. M. Bjorkegren, Manfred Boehm, Jacob Fog Bentzon, Valentin Fuster, Ha Won Kim, Neal L. Weintraub, Andrew H. Baker, Emily Bernstein, Jason C. Kovacic
Summary: The study identified the importance of HDAC9 in promoting EndMT in atherosclerosis, suggesting that targeting HDAC9 may be beneficial for stabilizing plaques or slowing the progression of atherosclerotic disease.
JOURNAL OF CLINICAL INVESTIGATION
(2021)