Review
Cardiac & Cardiovascular Systems
Mandy O. J. Grootaert, Martin R. Bennett
Summary: Vascular smooth muscle cells play a key role in atherosclerosis by forming a protective fibrous cap and exhibiting various phenotypes that can affect plaque formation and stability. They are a larger proportion of atherosclerotic plaques than previously thought and their plasticity is regulated by various mechanisms.
CARDIOVASCULAR RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Gabriel Hoi-Huen Chan, Enoch Chan, Carsten Tsun-Ka Kwok, George Pak-Heng Leung, Simon Ming-Yuen Lee, Sai-Wang Seto
Summary: Ageing is a risk factor for degenerative diseases, including cardiovascular diseases. The tumor suppressor gene p53 may play a regulatory role in vascular remodeling, atherosclerosis, and pulmonary hypertension. Further studies are needed to fully understand the effects of p53 in cardiovascular function and its therapeutic potential.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fabienne Burger, Daniela Baptista, Aline Roth, Rafaela Fernandes da Silva, Fabrizio Montecucco, Francois Mach, Karim J. Brandt, Kapka Miteva
Summary: The study demonstrated that oxLDL-activated monocytes can directly affect VSMCs in a co-culture system, leading to reduced expression of certain markers and upregulation of others, as well as activation of caspase 1, secretion of IL-1 beta, and pyroptosis in VSMCs. The activation of VSMC NLRP3 inflammasome by monocytes may play a detrimental role in atherosclerotic plaque stability in human atherosclerosis, as evidenced by findings in both mice and human atherosclerotic plaques.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Joseph M. Miano, Edward A. Fisher, Mark W. Majesky
Summary: Studying the phenotypic modulation of vascular smooth muscle cells is crucial for understanding the pathogenesis of atherosclerosis and developing new therapies. Recent technological and conceptual advances shed light on the multifunctionality and plasticity of VSMCs.
Article
Biochemistry & Molecular Biology
Megumi Miyabe, Nobuhisa Nakamura, Tomokazu Saiki, Satoru Miyabe, Mizuho Ito, Sachiko Sasajima, Tomomi Minato, Tatsuaki Matsubara, Keiko Naruse
Summary: Atherosclerosis is a leading cause of death globally, and there is a correlation between periodontal disease and atherosclerosis. This study used Porphyromonas gingivalis-derived LPS (Pg-LPS) to investigate the proliferation and migration of human aortic smooth muscle cells (HASMCs). The results suggest that Pg-LPS promotes atherosclerosis through the activation of the TLR4-MAPK signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yu Jiang, Hai-Yan Qian
Summary: Atherosclerosis (AS) is the accumulation of lipids and inflammatory debris in the arterial wall, leading to gradual occlusion of the arterial lumen. Despite therapeutic advances, AS remains the most common cause of cardiovascular diseases and the main mechanism of death and disability worldwide. Vascular smooth muscle cells (VSMCs) play a crucial role in AS, with remarkable plasticity and involvement in various processes such as phenotypic transformation, proliferation, migration, calcification, and apoptosis. Transcription factors and complex interactions of conserved cis-regulatory elements are key in the transcriptional regulation of VSMC genes, and manipulating transcription factors can regulate the development of atherosclerotic lesions.
MOLECULAR MEDICINE
(2023)
Article
Engineering, Biomedical
Deborah D. Chin, Christopher Poon, Jonathan Wang, Johan Joo, Victor Ong, Zhangjingyi Jiang, Kayley Cheng, Anastasia Plotkin, Gregory A. Magee, Eun Ji Chung
Summary: The delivery of miR-145 micelles to VSMCs shows promise in mitigating atherosclerosis progression by altering cell phenotypes and reducing plaque growth. In mouse experiments, miR-145 micelles significantly inhibited the advancement of atherosclerosis.
Review
Cardiac & Cardiovascular Systems
Magnus Back, Jean-Baptiste Michel
Summary: This review discusses the role of phosphates in arterial and valvular calcification, as well as potential novel therapeutic approaches for calcification prevention.
CARDIOVASCULAR RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Sang-Ho Woo, Dongsoo Kyung, Seung Hyun Lee, Kyu Seong Park, Minkyu Kim, Kibyeong Kim, Hyo-Jung Kwon, Young-Suk Won, Inpyo Choi, Young-Jun Park, Du-Min Go, Jeong-Seop Oh, Won Kee Yoon, Seung Sam Paik, Ji Hyeon Kim, Yong-Hwan Kim, Jae-Hoon Choi, Dae-Yong Kim
Summary: This study reveals that TXNIP plays a regulatory role in the osteochondrogenic transition of vascular smooth muscle cells (VSMCs) and affects the occurrence of atherosclerotic calcification. The effects of TXNIP were analyzed through the phenotypes of Txnip(-/-) mice, Tagln-Cre; Txnip(flox/flox) mice, and mice transplanted with the bone marrow of Txnip(-/-) mice. The downregulation of TXNIP in human calcified atherosclerotic plaques was also confirmed through reanalysis of a public single-cell RNA-sequencing dataset. In vitro experiments showed that suppression of TXNIP promotes osteodifferentiation of VSMCs. These findings suggest that TXNIP regulates atherosclerotic calcification by suppressing bone morphogenetic protein signaling and inhibiting the transition of VSMCs toward an osteochondrogenic phenotype.
CIRCULATION RESEARCH
(2023)
Review
Hematology
Carmen Yap, Arnout Mieremet, Carlie J. M. de Vries, Dimitra Micha, Vivian de Waard
Summary: Multiple layers of vascular smooth muscle cells (vSMCs) form the media of blood vessels, providing structure and regulating blood flow. vSMCs exhibit high plasticity and can switch between different phenotypes, with a total of 6 phenotypes identified. The central dedifferentiated vSMC type is the mesenchymal-like phenotype, which can differentiate into various other cell types contributing to vascular disease.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Cell Biology
Genmao Cao, Xuezhen Xuan, Jie Hu, Ruijing Zhang, Haijiang Jin, Honglin Dong
Summary: Vascular smooth muscle cells (VSMCs) are highly plastic and can switch into synthetic VSMCs to repair vascular injury. Multiple phenotypes of VSMCs have been discovered in vascular aging, atherosclerosis, and aortic aneurysm. The transformation of VSMCs is regulated by various factors such as transcription factors, growth factors, and non-coding RNAs.
CELL COMMUNICATION AND SIGNALING
(2022)
Review
Cell Biology
Jiali Yao, Linqian Cai, Yingrui Chen, Jie Zhang, Wenwen Zhuang, Jingyan Liang, Hongliang Li
Summary: This review discusses the impact of Exosomes on atherosclerosis (AS) from different perspectives, focusing on the phenotypic transition of vascular smooth muscle cells (VSMCs). It provides insights into the current status and potential future directions in this field, offering new ideas for clinical research and treatment of AS.
CELL COMMUNICATION AND SIGNALING
(2022)
Review
Hematology
Ashish Misra, Rajan Rehan, Alexander Lin, Sanjay Patel, Edward A. Fisher
Summary: Clonal expansion plays a crucial role in atherosclerosis, particularly in smooth muscle cells and macrophages. Recent studies have revealed the contribution of clonal expansion to disease pathology and provided innovative directions for future therapies of atherosclerosis and associated cardiovascular diseases.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Peripheral Vascular Disease
Lauren C. Chasland, Louise H. Naylor, Bu B. Yeap, Andrew J. Maiorana, Daniel J. Green
Summary: Exercise training improves endothelium-dependent vasodilator function in middle-to-older-aged men with central adiposity and low/normal testosterone levels, while administration of testosterone at therapeutic doses does not directly impact vascular function and does not add to the benefits of exercise.
Article
Cardiac & Cardiovascular Systems
Floriana Maria Farina, Simone Serio, Ignacio Fernando Hall, Stefania Zani, Giada Andrea Cassanmagnago, Montserrat Climent, Efrem Civilini, Gianluigi Condorelli, Manuela Quintavalle, Leonardo Elia
Summary: DOT1L inhibition in VSMCs significantly reduces atherosclerosis progression by directly modulating Nf-kappa B1 and Nf-kappa B2 transcription, which are master regulators of inflammation inducing expression of CCL5 and CXCL10 cytokines, key in atherosclerosis development. DOT1L could be a promising therapeutic target for vascular diseases as its inhibition reduces plaque progression.
EUROPEAN HEART JOURNAL
(2022)
Article
Physiology
Melise M. Edwards, Ha K. Nguyen, Adam J. Herbertson, Andrew D. Dodson, Tomasz Wietecha, Tami Wolden-Hanson, James L. Graham, Kevin D. O'Brien, Peter J. Havel, James E. Blevins
Summary: Chronic hindbrain oxytocin (OT) treatment leads to sustained weight loss in diet-induced obese (DIO) mice by reducing energy intake and increasing brown adipose tissue (BAT) thermogenesis at a dosage that does not cause visceral illness.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2021)
Editorial Material
Endocrinology & Metabolism
Maria J. Redondo, Ingrid Libman, David M. Maahs, Sarah K. Lyons, Mindy Saraco, Jane Reusch, Henry Rodriguez, Linda A. DiMeglio
Summary: The American Diabetes Association 2020 Standards of Medical Care in Diabetes recommend setting individualized A1C targets for children with type 1 diabetes, emphasizing the detrimental effects of hyperglycemia in children and adolescents. It is suggested that the use of newer insulins and devices may reduce the risk of severe hypoglycemia.
Article
Hematology
Alan Chait, Shari Wang, Leela Goodspeed, Diego Gomes, Katherine E. Turk, Tomasz Wietecha, Jingjing Tang, Carl Storey, Kevin D. O'Brien, Katya B. Rubinow, Chongren Tang, Tomas Vaisar, Sina A. Gharib, Aldons J. Lusis, Laura J. Den Hartigh
Summary: Saa3 promotes atherosclerosis in male mice but is atheroprotective in female mice, which may be related to sex-specific relationships between Saa3, sex steroid signaling, inflammatory genes, and Trem2 macrophages.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Peripheral Vascular Disease
Mary O. Whipple, Kevin S. Masters, Amy G. Huebschmann, Rebecca L. Scalzo, Jane E. B. Reusch, Audrey Bergouignan, Judith G. Regensteiner
Summary: This systematic review evaluates the acute effects of interrupting prolonged sedentary behavior on vascular health among individuals at risk for type 2 diabetes. The evidence suggests that light and moderate intensity activity breaks can acutely lower blood pressure, but further research is needed to understand the impact on other vascular outcomes.
Article
Hematology
Graziella E. Ronsein, Tomas Vaisar, W. Sean Davidson, Karin E. Bornfeldt, Jeffrey L. Probstfield, Kevin D. O'Brien, Xue-Qiao Zhao, Jay W. Heinecke
Summary: Niacin therapy does not reduce cardiovascular events in statin-treated subjects, despite increasing HDL-C levels and decreasing LDL-C and triglyceride levels. The addition of niacin to statin therapy results in elevated levels of multiple HDL proteins linked to increased atherosclerotic risk, potentially compromising the cardioprotective effects associated with higher HDL-C levels and lower levels of LDL-C and triglycerides.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Editorial Material
Endocrinology & Metabolism
Darleen A. Sandoval, Laura C. Alonso, Maureen Gannon, Maike Sander, Lori Sussel, Jane E. B. Reusch
Article
Biochemistry & Molecular Biology
Diego Gomes, Shari Wang, Leela Goodspeed, Katherine E. Turk, Tomasz Wietecha, Yongjun Liu, Karin E. Bornfeldt, Kevin D. O'Brien, Alan Chait, Laura J. den Hartigh
Summary: Ldlr-ASO is a promising tool for generating complex rodent models of atherosclerosis, but it does not induce comparable levels of hypercholesterolemia or atherosclerosis as Ldlr(-/-) mice and increases hepatic inflammation.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Urology & Nephrology
Benjamin Lidgard, Leila R. Zelnick, Kevin D. O'Brien, Nisha Bansal
Summary: In a large ambulatory cohort of adults with CKD, symptoms of atherosclerotic cardiovascular disease were strongly associated with a higher risk for subsequent myocardial infarction, including chest pain and shortness of breath.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Benjamin Lidgard, Leila R. Zelnick, Alan Go, Kevin D. O'Brien, Nisha Bansal
Summary: This study aimed to evaluate the effectiveness of atherosclerotic cardiovascular disease screening tools and clinically available cardiac biomarkers in guiding primary prevention in patients with chronic kidney disease. The results showed that the Framingham Risk Score and the Pooled Cohort Equation had moderate discrimination in predicting atherosclerotic cardiovascular disease, and the addition of hsTnT improved their discrimination. However, N-terminal pro-brain-type natriuretic peptide did not significantly improve the discrimination of the risk scores.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Editorial Material
Hematology
Kevin D. O'Brien
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Claudio A. Bravo, Andrew G. Navarro, Karanpreet K. Dhaliwal, Maziar Khorsandi, Jeffrey E. Keenan, Parvathi Mudigonda, Kevin D. O'Brien, Claudius Mahr
Summary: Left ventricular assist device (LVAD) therapy is a life-saving option for patients with advanced heart failure who do not respond to medical treatment. However, a significant percentage of LVAD patients develop right heart failure (RHF), which is associated with poor outcomes. The mechanisms of RHF are complex, involving patient factors, surgical factors, and hemodynamic factors. Despite advances in surgical techniques and LVAD technology, RHF remains a major cause of morbidity and mortality among LVAD patients. Current medical therapies for RHF are limited, and cardiac transplantation or supportive management are the only options for these patients. Efforts to predict the risk of RHF in LVAD patients have been challenging, with varying definitions of RHF in different studies. Additionally, most research in this field has focused on early-onset RHF, while late-onset RHF is increasingly recognized as a significant problem. This review aims to describe the unique physiology of the right ventricle and the changes caused by LVADs that may contribute to both early- and late-onset RHF. The available treatments for RHF, including mechanical circulatory support and medical therapies, will also be analyzed.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Dennis D. Wang, Sophia E. Airhart, Bo Zhou, Laura M. Shireman, Siyi Jiang, Carolina Melendez Rodriguez, James N. Kirkpatrick, Danny D. Shen, Rong Tian, Kevin D. O'Brien
Summary: Mitochondrial dysfunction in heart failure is associated with changes in NAD(+) and NADH levels. Raising NAD(+) levels using nicotinamide riboside (NR) may be a promising treatment for heart failure. In a trial involving 30 clinically stable heart failure patients, NR at a dose of 1,000 mg twice daily was found to be safe and well tolerated, and it approximately doubled whole blood NADthorn levels. The increase in NAD(+) in response to NR correlated with improved peripheral blood mononuclear cell respiration and reduced NLRP3 expression.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2022)
Article
Cardiac & Cardiovascular Systems
Xue-Qiao Zhao, Jie Sun, Daniel S. Hippe, Daniel A. Isquith, Gador Canton, Kiyofumi Yamada, Niranjan Balu, John R. Crouse, Todd J. Anderson, John Huston, Kevin D. O'Brien, Thomas S. Hatsukami, Chun Yuan
Summary: This study examined the impact of intraplaque hemorrhage (IPH) on lipid content change in the setting of intensive lipid-lowering therapy. The results indicate that IPH significantly affects lipid content change and is associated with plaque stability.
CIRCULATION-CARDIOVASCULAR IMAGING
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Andrew G. Navarro, Antonio Olivas-Martinez, Lorenzo Braghieri, Song Li, Claudius Mahr, Rong Tian, Kevin D. O'Brien, Claudio A. Bravo
Letter
Urology & Nephrology
Alexander J. Kula, David K. Prince, Bryan R. Kestenbaum, Song Li, Kevin D. O'Brien, Nisha Bansal