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Biology
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Immunology and Immunotherapy in Cardiovascular Disease
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Immunology and Immunotherapy in Cardiovascular Disease

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 19036

Special Issue Editors

Dr. Jiong-Wei Wang

E-Mail Website
Guest Editor
Cardiovascular Research Institute, Department of Surgery and Department of Physiology, National University of Singapore, Singapore
Interests: cardiovascular immunology and cardiac remodeling; drug delivery; extracellular vesicles; animal models and imaging
Dr. Elise L. Kessler

E-Mail Website
Guest Editor
1. Laboratory of Experimental Cardiology, University Medical Center Utrecht, The Netherlands
2. the Netherlands Heart Institute; and the Cardiology Department at the Charité, Berlin, Germany
Interests: cardiology; heart failure; HFpEF; cardiac electrophysiology; sex-differences; in vitro models; 3D models; inflammation; iPSC-differentiations; fibrosis
Dr. Yanan Wang

E-Mail Website
Guest Editor
Dept. of Endocrinology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China; Dept. of Medicine, Div. of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
Interests: Gut microbiota; metabolites short-chain fatty acids; and brown adipose tissue in obesity and atherosclerosis.

Special Issue Information

Cardiovascular disease remains the leading cause of mortality and morbidity. The critical involvement of both innate and adaptive immune systems in cardiovascular inflammatory responses is being recognized and the therapies targeting various immune cells are being proposed for the treatment of cardiovascular diseases including atherosclerosis, myocardial infarction, and stroke. Therefore, we are pleased to launch this Special Issue on the topic of “Immunology and Immunotherapy in Cardiovascular Disease”.

This Special Issue will include original research articles, high-quality meta-analysis, and state-of-the-art reviews discussing recent advances in the field. We welcome both fundamental and clinical research. If you are interested in contributing to this issue, please feel free to contact us prior to your submission of a full manuscript.

Dr. Jiong-Wei Wang
Dr. Elise L. Kessler
Dr. Yanan Wang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Research

Jump to: Review

11 pages, 1367 KiB  
Article
Elevated Plasma Immunoglobulin Levels Prior to Heart Transplantation Are Associated with Poor Post-Transplantation Survival
by Patricia van den Hoogen, Manon M. H. Huibers, Floor W. van den Dolder, Roel de Weger, Erica Siera-de Koning, Marish I. F. Oerlemans, Nicolaas de Jonge, Linda W. van Laake, Pieter A. Doevendans, Joost. P. G. Sluijter, Aryan Vink and Saskia C. A. de Jager
Biology 2023, 12(1), 61; https://doi.org/10.3390/biology12010061 - 30 Dec 2022
Viewed by 1715
Abstract
Cardiac allograft vasculopathy (CAV) and antibody-mediated rejection are immune-mediated, long-term complications that jeopardize graft survival after heart transplantation (HTx). Interestingly, increased plasma levels of immunoglobulins have been found in end-stage heart failure (HF) patients prior to HTx. In this study, we aimed to [...] Read more.
Cardiac allograft vasculopathy (CAV) and antibody-mediated rejection are immune-mediated, long-term complications that jeopardize graft survival after heart transplantation (HTx). Interestingly, increased plasma levels of immunoglobulins have been found in end-stage heart failure (HF) patients prior to HTx. In this study, we aimed to determine whether increased circulating immunoglobulin levels prior to transplantation are associated with poor post-HTx survival. Pre-and post-HTx plasma samples of 36 cardiac transplant recipient patients were used to determine circulating immunoglobulin levels. In addition, epicardial tissue was collected to determine immunoglobulin deposition in cardiac tissue and assess signs and severity of graft rejection. High levels of IgG1 and IgG2 prior to HTx were associated with a shorter survival post-HTx. Immunoglobulin deposition in cardiac tissue was significantly elevated in patients with a survival of less than 3 years. Patients with high plasma IgG levels pre-HTx also had significantly higher plasma levels after HTx. Furthermore, high pre-HTX levels of IgG1 and IgG2 levels were also significantly increased in patients with inflammatory infiltrate in CAV lesions. Altogether the results of this proof-of-concept study suggest that an activated immune response prior to transplantation negatively affects graft survival. Full article
(This article belongs to the Special Issue Immunology and Immunotherapy in Cardiovascular Disease)
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11 pages, 306300 KiB  
Communication
Neonatal Subcutaneous BCG Vaccination Decreases Atherosclerotic Plaque Number and Plaque Macrophage Content in ApoE−/− Mice
by Siroon Bekkering, Krishan Singh, Hui Lu, Albert P. Limawan, Claudia A. Nold-Petry, Megan J. Wallace, Nigel Curtis, Salvatore Pepe, Michael Cheung, David P. Burgner and Timothy Moss
Biology 2022, 11(10), 1511; https://doi.org/10.3390/biology11101511 - 15 Oct 2022
Cited by 1 | Viewed by 2321
Abstract
Bacille-Calmette Guérin (BCG) modulates atherosclerosis development in experimental animals, but it remains unclear whether neonatal BCG vaccination is pro- or anti-atherogenic. Many animal models differ fundamentally from BCG administration to human infants in terms of age, vaccine preparation, dosing schedule, and route of [...] Read more.
Bacille-Calmette Guérin (BCG) modulates atherosclerosis development in experimental animals, but it remains unclear whether neonatal BCG vaccination is pro- or anti-atherogenic. Many animal models differ fundamentally from BCG administration to human infants in terms of age, vaccine preparation, dosing schedule, and route of administration. We aimed to elucidate the effect of neonatal subcutaneous BCG vaccination—analogous to human BCG vaccination—on atherosclerosis development in ApoE−/− mice. At 2 days of age, a total of 40 ApoE−/− mice received either a weight-equivalent human dose of BCG, or saline, subcutaneously. From 4 weeks onwards, the mice were fed a Western-type diet containing 22% fat. At 16 weeks of age, mice were sacrificed for the assessment of atherosclerosis. Body weight, plasma lipids, atherosclerosis lesion size and collagen content were similar in both groups. Atherosclerosis lesion number was lower in mice that received BCG. Macrophage content was 20% lower in the BCG-vaccinated mice (p < 0.05), whereas plaque lipid content was increased by 25% (p < 0.01). In conclusion, neonatal BCG vaccination reduces atherosclerosis plaque number and macrophage content but increases lipid content in a murine model of atherosclerosis. Human epidemiological and mechanistic studies are warranted to investigate whether neonatal BCG vaccination is potentially atheroprotective. Full article
(This article belongs to the Special Issue Immunology and Immunotherapy in Cardiovascular Disease)
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14 pages, 4062 KiB  
Article
Soluble Flt-1 in AMI Patients Serum Inhibits Angiogenesis of Endothelial Progenitor Cells by Suppressing Akt and Erk’s Activity
by Lijie Zhang, Xingkun Zhang, Xiaoming Zhong, Mengya Fan, Guoliang Wang, Wei Shi, Ran Xie, Yinxiang Wei, Hailong Zhang, Xiangxu Meng, Yaohui Wang and Yuanfang Ma
Biology 2022, 11(8), 1194; https://doi.org/10.3390/biology11081194 - 09 Aug 2022
Viewed by 1586
Abstract
In acute myocardial infarction (AMI), endothelial progenitor cells (EPCs) are essential for the recovery of collateral circulation via angiogenesis. Clinical research has shown that the poor prognosis of the patients with AMI is closely associated with the cell quantity and function of EPCs. [...] Read more.
In acute myocardial infarction (AMI), endothelial progenitor cells (EPCs) are essential for the recovery of collateral circulation via angiogenesis. Clinical research has shown that the poor prognosis of the patients with AMI is closely associated with the cell quantity and function of EPCs. Whether there are differences in the biological features of EPCs from AMI patients and healthy subjects is worth exploring. In this study, EPCs were isolated from human peripheral blood and identified as late-stage EPCs by flow cytometry, immunofluorescence, and blood vessel formation assay. Compared to healthy subjects, AMI patients had more EPCs in the peripheral blood compared to healthy subjects. In addition, EPCs from AMI patients exhibited higher migration ability in the transwell assay compared to EPCs from healthy subjects. However, no difference in the angiogenesis of EPCs was observed between AMI patients and healthy subjects. Further studies revealed that soluble vascular endothelial growth factor receptor 1 (sFlt-1) in the serum of AMI patients was involved in the inhibition of EPCs angiogenesis by suppressing the Akt and Erk pathways. In conclusion, this study demonstrated that elevated serum sFlt-1 inhibits angiogenesis of EPC in AMI patients. Our findings uncover a pathogenic role of sFlt-1 in AMI. Full article
(This article belongs to the Special Issue Immunology and Immunotherapy in Cardiovascular Disease)
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19 pages, 1813 KiB  
Article
PhIP-Seq Reveals Autoantibodies for Ubiquitously Expressed Antigens in Viral Myocarditis
by Mahima T. Rasquinha, Ninaad Lasrado, Erika Petro-Turnquist, Eric Weaver, Thiagarajan Venkataraman, Daniel Anderson, Uri Laserson, H. Benjamin Larman and Jay Reddy
Biology 2022, 11(7), 1055; https://doi.org/10.3390/biology11071055 - 13 Jul 2022
Cited by 5 | Viewed by 3386
Abstract
Enteroviruses such as group B coxsackieviruses (CVB) are commonly suspected as causes of myocarditis that can lead to dilated cardiomyopathy (DCM), and the mouse model of CVB3 myocarditis is routinely used to understand DCM pathogenesis. Mechanistically, autoimmunity is suspected due to the presence [...] Read more.
Enteroviruses such as group B coxsackieviruses (CVB) are commonly suspected as causes of myocarditis that can lead to dilated cardiomyopathy (DCM), and the mouse model of CVB3 myocarditis is routinely used to understand DCM pathogenesis. Mechanistically, autoimmunity is suspected due to the presence of autoantibodies for select antigens. However, their role continues to be enigmatic, which also raises the question of whether the breadth of autoantibodies is sufficiently characterized. Here, we attempted to comprehensively analyze the autoantibody repertoire using Phage ImmunoPrecipitation Sequencing (PhIP-Seq), a versatile and high-throughput platform, in the mouse model of CVB3 myocarditis. First, PhIP-Seq analysis using the VirScan library revealed antibody reactivity only to CVB3 in the infected group but not in controls, thus validating the technique in this model. Second, using the mouse peptide library, we detected autoantibodies to 32 peptides from 25 proteins in infected animals that are ubiquitously expressed and have not been previously reported. Third, by using ELISA as a secondary assay, we confirmed antibody reactivity in sera from CVB3-infected animals to cytochrome c oxidase assembly factor 4 homolog (COA4) and phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), indicating the specificity of antibody detection by PhIP-Seq technology. Fourth, we noted similar antibody reactivity patterns in CVB3 and CVB4 infections, suggesting that the COA4- and PIK3AP1-reactive antibodies could be common to multiple CVB infections. The specificity of the autoantibodies was affirmed with influenza-infected animals that showed no reactivity to any of the antigens tested. Taken together, our data suggest that the autoantibodies identified by PhIP-Seq may have relevance to CVB pathogenesis, with a possibility that similar reactivity could be expected in human DCM patients. Full article
(This article belongs to the Special Issue Immunology and Immunotherapy in Cardiovascular Disease)
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12 pages, 968 KiB  
Article
Neutrophil-to-Lymphocyte Ratio Is Not Associated with Severity of Coronary Artery Disease and Is Not Correlated with Vitamin D Level in Patients with a History of an Acute Coronary Syndrome
by Ewelina A. Dziedzic, Jakub S. Gąsior, Agnieszka Tuzimek, Marek Dąbrowski and Piotr Jankowski
Biology 2022, 11(7), 1001; https://doi.org/10.3390/biology11071001 - 01 Jul 2022
Cited by 8 | Viewed by 2752
Abstract
Coronary artery disease (CAD), the leading cause of death worldwide, has an underlying cause in atherosclerosis. The activity of this inflammatory process can be measured with neutrophil-to-lymphocyte ratio (NLR). The anti-inflammatory and anti-atherogenic properties of vitamin D affect many mechanisms involved in CAD. [...] Read more.
Coronary artery disease (CAD), the leading cause of death worldwide, has an underlying cause in atherosclerosis. The activity of this inflammatory process can be measured with neutrophil-to-lymphocyte ratio (NLR). The anti-inflammatory and anti-atherogenic properties of vitamin D affect many mechanisms involved in CAD. In this study, we investigated the association between NLR, vitamin D concentration, and severity of CAD in a group of patients with a history of myocardial infarction (MI). NLR was higher in patients with acute coronary syndrome (ACS) in comparison to those with stable CAD (median: 2.8, range: 0.96–24.3 vs. median: 2.3, range: 0.03–31.6; p < 0.05). No associations between NLR and severity of CAD (p = 0.14) in the cohort and in the subgroups with stable CAD (p = 0.40) and ACS (p = 0.34) were observed. We found no correlation between vitamin D level and NLR neither in the whole study group (p = 0.29) nor in subgroups of patients with stable CAD (p = 0.84) and ACS (p = 0.30). NLR could be used as prognostic biomarker of consecutive MI in patients with CAD and a history of MI. Full article
(This article belongs to the Special Issue Immunology and Immunotherapy in Cardiovascular Disease)
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Review

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22 pages, 2208 KiB  
Review
Exosomal Non-Coding RNA Mediates Macrophage Polarization: Roles in Cardiovascular Diseases
by Hongyun Wang, Xuan Ye, Michail Spanos, Huanxin Wang, Zijiang Yang, Guoping Li, Junjie Xiao and Lei Zhou
Biology 2023, 12(5), 745; https://doi.org/10.3390/biology12050745 - 19 May 2023
Cited by 3 | Viewed by 1623
Abstract
Extracellular vesicles (EVs) or exosomes are nanosized extracellular particles that contain proteins, DNA, non-coding RNA (ncRNA) and other molecules, which are widely present in biofluids throughout the body. As a key mediator of intercellular communication, EVs transfer their cargoes to target cells and [...] Read more.
Extracellular vesicles (EVs) or exosomes are nanosized extracellular particles that contain proteins, DNA, non-coding RNA (ncRNA) and other molecules, which are widely present in biofluids throughout the body. As a key mediator of intercellular communication, EVs transfer their cargoes to target cells and activate signaling transduction. Increasing evidence shows that ncRNA is involved in a variety of pathological and physiological processes through various pathways, particularly the inflammatory response. Macrophage, one of the body’s “gatekeepers”, plays a crucial role in inflammatory reactions. Generally, macrophages can be classified as pro-inflammatory type (M1) or anti-inflammatory type (M2) upon their phenotypes, a phenomenon termed macrophage polarization. Increasing evidence indicates that the polarization of macrophages plays important roles in the progression of cardiovascular diseases (CVD). However, the role of exosomal ncRNA in regulating macrophage polarization and the role of polarized macrophages as an important source of EV in CVD remains to be elucidated. In this review, we summarize the role and molecular mechanisms of exosomal-ncRNA in regulating macrophage polarization during CVD development, focusing on their cellular origins, functional cargo, and their detailed effects on macrophage polarization. We also discuss the role of polarized macrophages and their derived EV in CVD as well as the therapeutic prospects of exosomal ncRNA in the treatment of CVD. Full article
(This article belongs to the Special Issue Immunology and Immunotherapy in Cardiovascular Disease)
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18 pages, 391 KiB  
Review
Immunomodulatory Potential of Diuretics
by Paweł Bryniarski, Katarzyna Nazimek and Janusz Marcinkiewicz
Biology 2021, 10(12), 1315; https://doi.org/10.3390/biology10121315 - 11 Dec 2021
Cited by 4 | Viewed by 4216
Abstract
In this review, diuretics and their immunomodulatory functions are described. The effects on the immune response of this group of drugs are reported in patients suffering from hypertension and under experimental conditions involving animal models and cell line studies. The pathogenesis of hypertension [...] Read more.
In this review, diuretics and their immunomodulatory functions are described. The effects on the immune response of this group of drugs are reported in patients suffering from hypertension and under experimental conditions involving animal models and cell line studies. The pathogenesis of hypertension is strongly connected to chronic inflammation. The vast majority of diuretics modulate the immune response, changing it in favor of the anti-inflammatory response, but depending on the drug, these effects may differ. This topic is significantly important in medical practice regarding the treatment of patients who have coexisting diseases with chronic inflammatory pathogenesis, including hypertension or chronic heart failure. In patients with metabolic syndrome, allergies, or autoimmune disorders, the anti-inflammatory effect is favorable, because of the overstimulation of their immune system. Otherwise, in the geriatric population, it is important to find the proper anti- and pro-inflammatory balance to avoid an enhancement of immune response suppression, which can result in reducing the risk of serious infections that can occur due to the age-diminished function of the immune system. This article is intended to facilitate the selection of an antihypertensive drug that depends on the patient’s immune situation. Full article
(This article belongs to the Special Issue Immunology and Immunotherapy in Cardiovascular Disease)
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