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Special Issue "Molecular Research on Arteriosclerosis and Thrombosis"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 August 2021.

Special Issue Editor

Prof. Dr. Katrin Schäfer
E-Mail Website
Guest Editor
Center for Cardiology, Cardiology I; University Medical Center Mainz, Mainz, Germany
Interests: adipokines; neointima formation; obesity; thrombosis; vascular remodeling

Special Issue Information

Dear Colleagues,

Cardiovascular disease continues to be a major cause of death and disease. Over the last few decades, clinical and experimental research has identified key cellular players and molecular mediators involved in atherosclerotic lesion initiation, progression, and ultimately, plaque rupture and thrombosis. More recently, evidence is accumulating on the importance of the perivascular adipose tissue surrounding blood vessels as a modulator of disease severity and how this interaction is affected by metabolic stressors, such as obesity, diabetes or age. In addition to traditional risk factors, endogenous and environmental conditions have emerged that impact on cardiovascular risk and atherosclerosis progression, including the gut microbiome, dietary factors, and air or noise pollutants.

The Special Issue on “Molecular Research on Arteriosclerosis and Thrombosis” will comprise a selection of original research papers and reviews focusing on, but not limited to, novel findings and developments on the molecular mechanisms, cell-cell interactions, and internal or external stressors involved in pathophysiology of atherosclerosis and thrombosis. This will include experimental studies in animal models of atherosclerosis, thrombosis, and plaque rupture using transgenic mice with global or cell-specific genetic modifications or exposed to specific risk factors or therapeutic regimens. Molecular imaging studies on novel targets or cell culture work examining novel diagnostic or therapeutic candidates are also welcome.

Prof. Katrin Schäfer
Guest Editor

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 papers will be 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Keywords

  • Atherosclerosis
  • Neointima formation
  • Thrombosis
  • Animal models
  • Perivascular adipose tissue
  • Endothelial cells
  • Smooth muscle cells
  • Platelets
  • Inflammation
  • Plaque erosion
  • Plaque rupture

Published Papers (8 papers)

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Research

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Open AccessArticle
Vascular Inflammation and Dysfunction in Lupus-Prone Mice-IL-6 as Mediator of Disease Initiation
Int. J. Mol. Sci. 2021, 22(5), 2291; https://doi.org/10.3390/ijms22052291 - 25 Feb 2021
Viewed by 309
Abstract
Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable [...] Read more.
Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients. Methods: Here we investigated whether MRL-Faslpr mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-Faslpr, MRL-++, and previously generated Il6−/− MRL-Faslpr mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage. Results: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation. Conclusion: Our findings demonstrate that the MRL-Faslpr mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE. Full article
(This article belongs to the Special Issue Molecular Research on Arteriosclerosis and Thrombosis)
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Open AccessArticle
Calciprotein Particles Cause Endothelial Dysfunction under Flow
Int. J. Mol. Sci. 2020, 21(22), 8802; https://doi.org/10.3390/ijms21228802 - 20 Nov 2020
Cited by 1 | Viewed by 452
Abstract
Calciprotein particles (CPPs), which increasingly arise in the circulation during the disorders of mineral homeostasis, represent a double-edged sword protecting the human organism from extraskeletal calcification but potentially causing endothelial dysfunction. Existing models, however, failed to demonstrate the detrimental action of CPPs on [...] Read more.
Calciprotein particles (CPPs), which increasingly arise in the circulation during the disorders of mineral homeostasis, represent a double-edged sword protecting the human organism from extraskeletal calcification but potentially causing endothelial dysfunction. Existing models, however, failed to demonstrate the detrimental action of CPPs on endothelial cells (ECs) under flow. Here, we applied a flow culture system, where human arterial ECs were co-incubated with CPPs for 4 h, and a normolipidemic and normotensive rat model (10 daily intravenous injections of CPPs) to simulate the scenario occurring in vivo in the absence of confounding cardiovascular risk factors. Pathogenic effects of CPPs were investigated by RT-qPCR and Western blotting profiling of the endothelial lysate. CPPs were internalised within 1 h of circulation, inducing adhesion of peripheral blood mononuclear cells to ECs. Molecular profiling revealed that CPPs stimulated the expression of pro-inflammatory cell adhesion molecules VCAM1 and ICAM1 and upregulated transcription factors of endothelial-to-mesenchymal transition (Snail, Slug and Twist1). Furthermore, exposure to CPPs reduced the production of atheroprotective transcription factors KLF2 and KLF4 and led to YAP1 hypophosphorylation, potentially disturbing the mechanisms responsible for the proper endothelial mechanotransduction. Taken together, our results suggest the ability of CPPs to initiate endothelial dysfunction at physiological flow conditions. Full article
(This article belongs to the Special Issue Molecular Research on Arteriosclerosis and Thrombosis)
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Open AccessArticle
Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice
Int. J. Mol. Sci. 2020, 21(14), 4916; https://doi.org/10.3390/ijms21144916 - 12 Jul 2020
Viewed by 743
Abstract
Myeloid cells are crucial for the development of vascular inflammation. Low-density lipoprotein receptor-related protein 8 (LRP8) or Apolipoprotein E receptor 2 (ApoER2), is expressed by macrophages, endothelial cells and platelets and has been implicated in the development of cardiovascular diseases. Our aim was [...] Read more.
Myeloid cells are crucial for the development of vascular inflammation. Low-density lipoprotein receptor-related protein 8 (LRP8) or Apolipoprotein E receptor 2 (ApoER2), is expressed by macrophages, endothelial cells and platelets and has been implicated in the development of cardiovascular diseases. Our aim was to evaluate the role of LRP8, in particular from immune cells, in the development of vascular inflammation. Methods. LRP8+/+ and LRP8−/− mice (on B6;129S background) were infused with angiotensin II (AngII, 1 mg/kg/day for 7 to 28 day) using osmotic minipumps. Blood pressure was recorded using tail cuff measurements. Vascular reactivity was assessed in isolated aortic segments. Leukocyte activation and infiltration were assessed by flow cytometry of aortic tissue and intravital videomicroscopy imaging. Histological analysis of aortic sections was conducted using sirius red staining. Results. AngII infusion worsened endothelial-dependent vascular relaxation and immune cells rolling and adherence to the carotid artery in both LRP8+/+ as well as LRP8−/− mice. However, only LRP8−/− mice demonstrated a drastically increased mortality rate in response to AngII due to aortic dissection. Bone marrow transplantation revealed that chimeras with LRP8 deficient myeloid cells phenocopied LRP8−/− mice. Conclusion. AngII-infused LRP8 deficient mice could be a useful animal model to study aortic dissection reflecting the lethality of this disease in humans. Full article
(This article belongs to the Special Issue Molecular Research on Arteriosclerosis and Thrombosis)
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Review

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Open AccessReview
Pathophysiology of Atherosclerotic Plaque Development-Contemporary Experience and New Directions in Research
Int. J. Mol. Sci. 2021, 22(7), 3513; https://doi.org/10.3390/ijms22073513 - 29 Mar 2021
Viewed by 475
Abstract
Atherosclerotic plaque is the pathophysiological basis of important and life-threatening diseases such as myocardial infarction. Although key aspects of the process of atherosclerotic plaque development and progression such as local inflammation, LDL oxidation, macrophage activation, and necrotic core formation have already been discovered, [...] Read more.
Atherosclerotic plaque is the pathophysiological basis of important and life-threatening diseases such as myocardial infarction. Although key aspects of the process of atherosclerotic plaque development and progression such as local inflammation, LDL oxidation, macrophage activation, and necrotic core formation have already been discovered, many molecular mechanisms affecting this process are still to be revealed. This minireview aims to describe the current directions in research on atherogenesis and to summarize selected studies published in recent years—in particular, studies on novel cellular pathways, epigenetic regulations, the influence of hemodynamic parameters, as well as tissue and microorganism (microbiome) influence on atherosclerotic plaque development. Finally, some new and interesting ideas are proposed (immune cellular heterogeneity, non-coding RNAs, and immunometabolism) which will hopefully bring new discoveries in this area of investigation. Full article
(This article belongs to the Special Issue Molecular Research on Arteriosclerosis and Thrombosis)
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Open AccessReview
Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis
Int. J. Mol. Sci. 2021, 22(2), 676; https://doi.org/10.3390/ijms22020676 - 12 Jan 2021
Viewed by 697
Abstract
Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings [...] Read more.
Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock. Full article
(This article belongs to the Special Issue Molecular Research on Arteriosclerosis and Thrombosis)
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Open AccessReview
Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability
Int. J. Mol. Sci. 2020, 21(11), 3946; https://doi.org/10.3390/ijms21113946 - 31 May 2020
Cited by 7 | Viewed by 858
Abstract
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling and degradation of extracellular matrix (ECM) proteins. MMPs may modulate various cellular and signaling pathways in atherosclerosis responsible for progression and rupture of atherosclerotic plaques. The effect of MMPs polymorphisms [...] Read more.
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling and degradation of extracellular matrix (ECM) proteins. MMPs may modulate various cellular and signaling pathways in atherosclerosis responsible for progression and rupture of atherosclerotic plaques. The effect of MMPs polymorphisms and the expression of MMPs in both the atherosclerotic plaque and plasma was shown. They are independent predictors of atherosclerotic plaque instability in stable coronary heart disease (CHD) patients. Increased levels of MMPs in patients with advanced cardiovascular disease (CAD) and acute coronary syndrome (ACS) was associated with future risk of cardiovascular events. These data confirm that MMPs may be biomarkers in plaque instability as they target in potential drug therapies for atherosclerosis. They provide important prognostic information, independent of traditional risk factors, and may turn out to be useful in improving risk stratification. Full article
(This article belongs to the Special Issue Molecular Research on Arteriosclerosis and Thrombosis)
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Open AccessReview
Exogenous NO Therapy for the Treatment and Prevention of Atherosclerosis
Int. J. Mol. Sci. 2020, 21(8), 2703; https://doi.org/10.3390/ijms21082703 - 13 Apr 2020
Cited by 8 | Viewed by 1258
Abstract
Amyl nitrite was introduced in 1867 as the first molecule of a new class of agents for the treatment of angina pectoris. In the following 150 years, the nitric oxide pathway has been the subject of a number of pharmacological approaches, particularly since [...] Read more.
Amyl nitrite was introduced in 1867 as the first molecule of a new class of agents for the treatment of angina pectoris. In the following 150 years, the nitric oxide pathway has been the subject of a number of pharmacological approaches, particularly since when this elusive mediator was identified as one of the most important modulators of vascular homeostasis beyond vasomotion, including platelet function, inflammation, and atherogenesis. While having potent antianginal and antiischemic properties, however, nitric oxide donors are also not devoid of side effects, including the induction of tolerance, and, as shown in the last decade, of oxidative stress and endothelial dysfunction. In turn, endothelial dysfunction is itself felt to be involved in all stages of atherogenesis, from the development of fatty streaks to plaque rupture and thrombosis. In the present review, we summarize the agents that act on the nitric oxide pathway, with a particular focus on their potentially beneficial antiatherosclerotic and unwanted pro-atherosclerotic effects. Full article
(This article belongs to the Special Issue Molecular Research on Arteriosclerosis and Thrombosis)
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Other

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Open AccessBrief Report
The Commensal Microbiota Enhances ADP-Triggered Integrin αIIbβ3 Activation and von Willebrand Factor-Mediated Platelet Deposition to Type I Collagen
Int. J. Mol. Sci. 2020, 21(19), 7171; https://doi.org/10.3390/ijms21197171 - 28 Sep 2020
Viewed by 636
Abstract
The commensal microbiota is a recognized enhancer of arterial thrombus growth. While several studies have demonstrated the prothrombotic role of the gut microbiota, the molecular mechanisms promoting arterial thrombus growth are still under debate. Here, we demonstrate that germ-free (GF) mice, which from [...] Read more.
The commensal microbiota is a recognized enhancer of arterial thrombus growth. While several studies have demonstrated the prothrombotic role of the gut microbiota, the molecular mechanisms promoting arterial thrombus growth are still under debate. Here, we demonstrate that germ-free (GF) mice, which from birth lack colonization with a gut microbiota, show diminished static deposition of washed platelets to type I collagen compared with their conventionally raised (CONV-R) counterparts. Flow cytometry experiments revealed that platelets from GF mice show diminished activation of the integrin αIIbβ3 (glycoprotein IIbIIIa) when activated by the platelet agonist adenosine diphosphate (ADP). Furthermore, washed platelets from Toll-like receptor-2 (Tlr2)-deficient mice likewise showed impaired static deposition to the subendothelial matrix component type I collagen compared with wild-type (WT) controls, a process that was unaffected by GPIbα-blockade but influenced by von Willebrand factor (VWF) plasma levels. Collectively, our results indicate that microbiota-triggered steady-state activation of innate immune pathways via TLR2 enhances platelet deposition to subendothelial matrix molecules. Our results link host colonization status with the ADP-triggered activation of integrin αIIbβ3, a pathway promoting platelet deposition to the growing thrombus. Full article
(This article belongs to the Special Issue Molecular Research on Arteriosclerosis and Thrombosis)
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