scholarly journals The Role of Fibroblasts in Atherosclerosis Progression

2021 ◽  
Author(s):  
Tadeja Kuret ◽  
Snežna Sodin-Šemrl
Keyword(s):  
Proteolytic Enzymes ◽  
Vascular Inflammation ◽  
Endothelial Activation ◽  
Quiescent State ◽  
Matrix Remodeling ◽  
New Paradigm ◽  
Functional Changes ◽  
Atherosclerosis Progression ◽  
Promising Therapeutic Approach ◽  
Adventitial Layer

The following chapter addresses vascular fibroblasts in a healthy, quiescent state, as well during vascular inflammation, focusing on atherosclerosis. The development of atherosclerosis, an inflammatory disease of medium- and large-sized arteries, has traditionally been viewed as an “inside-out” mechanism, with prominent roles of the innermost layer of the artery, consisting of endothelial cells. However, emerging evidence suggests a new paradigm of “outside-in” mechanism, including an earlier role for fibroblasts, constituents of the outermost adventitial layer of the artery. Phenotypic and functional changes of fibroblasts in adventitia may even occur prior to, or alongside endothelial activation. Activated adventitial fibroblasts, implicated in atherosclerosis progression, begin to transform into myofibroblasts, upregulate production of different proinflammatory cytokines, chemokines, growth factors, proteolytic enzymes, extracellular matrix proteins and reactive oxygen species, leading to extensive matrix remodeling, chemotaxis and recruitment of immune cells. Due to their suitable location for drug delivery systems, preventing fibroblast activation, modulating their activity or inducing myofibroblast dedifferentiation could represent a promising therapeutic approach for atherosclerosis regression.

scholarly journals Inflammatory Mechanisms Contributing to Endothelial Dysfunction

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 781
Author(s):  
Panagiotis Theofilis ◽  
Marios Sagris ◽  
Evangelos Oikonomou ◽  
Alexios S. Antonopoulos ◽  
Gerasimos Siasos ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Inflammatory Mediators ◽  
Leukocyte Adhesion ◽  
Vascular Inflammation ◽  
Endothelial Activation ◽  
Nuclear Factor Κb ◽  
Cellular Adhesion ◽  
Cell Integrity ◽  
Atherosclerosis Progression

Maintenance of endothelial cell integrity is an important component of human health and disease since the endothelium can perform various functions including regulation of vascular tone, control of hemostasis and thrombosis, cellular adhesion, smooth muscle cell proliferation, and vascular inflammation. Endothelial dysfunction is encompassed by complex pathophysiology that is based on endothelial nitric oxide synthase uncoupling and endothelial activation following stimulation from various inflammatory mediators (molecular patterns, oxidized lipoproteins, cytokines). The downstream signaling via nuclear factor-κB leads to overexpression of adhesion molecules, selectins, and chemokines that facilitate leukocyte adhesion, rolling, and transmigration to the subendothelial space. Moreover, oscillatory shear stress leads to pro-inflammatory endothelial activation with increased monocyte adhesion and endothelial cell apoptosis, an effect that is dependent on multiple pathways and flow-sensitive microRNA regulation. Moreover, the role of neutrophil extracellular traps and NLRP3 inflammasome as inflammatory mechanisms contributing to endothelial dysfunction has recently been unveiled and is under further investigation. Consequently, and following their activation, injured endothelial cells release inflammatory mediators and enter a pro-thrombotic state through activation of coagulation pathways, downregulation of thrombomodulin, and an increase in platelet adhesion and aggregation owing to the action of von-Willebrand factor, ultimately promoting atherosclerosis progression.

Targeting Trained Innate Immunity With Nanobiologics to Treat Cardiovascular Disease

2021 ◽  
Author(s):  
Abraham J.P. Teunissen ◽  
Mandy M.T. van Leent ◽  
Geoffrey Prevot ◽  
Eliane E.S. Brechbuhl ◽  
Carlos Pérez-Medina ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Apolipoprotein A1 ◽  
New Paradigm ◽  
Trained Immunity ◽  
Atherosclerosis Progression ◽  
Cardiovascular Patients ◽  
Cellular Pathways

The innate immune system plays a key role in atherosclerosis progression and the pathogenesis of cardiovascular disease. Trained immunity, an epigenetically regulated hyperresponsive state of myeloid cells, is a driving force underlying chronic inflammation in atherosclerosis. Therapeutically targeting innate trained immunity therefore may mature into a compelling new paradigm for the effective treatment of cardiovascular patients, which would require effective engagement of myeloid cells. For over a decade, we have worked on apolipoprotein A1-based nanomaterials, referred to as nanobiologics, which we have utilized for myeloid cell-directed immunotherapy. Here, we review the application of our nanobiologic immunotherapies in treating vascular disease. The design of nanobiologic therapeutics, as well as their use in targeting myeloid cells and cellular pathways related to trained immunity, is discussed. Furthermore, we show that nanobiologic biocompatibility and in vivo behavior are conserved across species, from mice to larger animals, including rabbits, pigs, and nonhuman primates. Last, we deliberate on the hurdles that currently prevent widespread translation of trained immunity targeting cardiovascular nanotherapies.

scholarly journals Circulating Endothelial Microparticles: A Key Hallmark of Atherosclerosis Progression

Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Keshav Raj Paudel ◽  
Nisha Panth ◽  
Dong-Wook Kim
Keyword(s):  
Vascular Function ◽  
Cell Activation ◽  
Vascular Inflammation ◽  
Rho Kinase ◽  
Disease Status ◽  
Endothelial Microparticles ◽  
Atherosclerosis Progression ◽  
Mitogen Activated Protein ◽  
Circulating Microparticles ◽  
Ros Formation

The levels of circulating microparticles (MPs) are raised in various cardiovascular diseases. Their increased level in plasma is regarded as a biomarker of alteration in vascular function. The prominent MPs present in blood are endothelial microparticles (EMPs) described as complex submicron (0.1 to 1.0 μm) vesicles like structure, released in response to endothelium cell activation or apoptosis. EMPs possess both physiological and pathological effects and may promote oxidative stress and vascular inflammation. EMPs release is triggered by inducer like angiotensin II, lipopolysaccharide, and hydrogen peroxide leading to the progression of atherosclerosis. However, there are multiple physiological pathways for EMPs generation like NADPH oxidase derived endothelial ROS formation, Rho kinase pathway, and mitogen-activated protein kinases. Endothelial dysfunction is a key initiating event in atherosclerotic plaque formation. Atheroemboli, resulting from ruptured carotid plaques, is a major cause of stroke. Increasing evidence suggests that EMPs play an important role in the pathogenesis of cardiovascular disease, acting as a marker of damage, either exacerbating disease progression or triggering a repair response. In this regard, it has been suggested that EMPs have the potential to act as biomarkers of disease status. This review aims to provide updated information of EMPs in relation to atherosclerosis pathogenesis.

scholarly journals Calcineurin inhibitors cyclosporine A and tacrolimus induce vascular inflammation and endothelial activation through TLR4 signaling

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Raquel Rodrigues-Diez ◽  
Cristian González-Guerrero ◽  
Carlos Ocaña-Salceda ◽  
Raúl R. Rodrigues-Diez ◽  
Jesús Egido ◽  
...  
Keyword(s):  
Cyclosporine A ◽  
Vascular Inflammation ◽  
Calcineurin Inhibitors ◽  
Endothelial Activation ◽  
Tlr4 Signaling

Regulation of Endothelial Activation and Vascular Inflammation by Shear Stress

2012 ◽  
pp. 77-85 ◽  
Author(s):  
Annapurna Nayak ◽  
Carola S. König ◽  
Uday Kishore ◽  
Paul C. Evans
Keyword(s):  
Shear Stress ◽  
Vascular Inflammation ◽  
Endothelial Activation

scholarly journals Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4652
Author(s):  
Barbara Kutryb-Zajac ◽  
Paulina Mierzejewska ◽  
Ewa M. Slominska ◽  
Ryszard T. Smolenski
Keyword(s):  
Adenosine Deaminase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Vascular Inflammation ◽  
Endothelial Activation ◽  
Enzymatic Function ◽  
Adenosine Uptake ◽  
Cardiovascular Pathologies ◽  
Ada Protein ◽  
Myocardial Ischemia Reperfusion

Adenosine deaminase (ADA) is an enzyme of purine metabolism that irreversibly converts adenosine to inosine or 2′deoxyadenosine to 2′deoxyinosine. ADA is active both inside the cell and on the cell surface where it was found to interact with membrane proteins, such as CD26 and adenosine receptors, forming ecto-ADA (eADA). In addition to adenosine uptake, the activity of eADA is an essential mechanism that terminates adenosine signaling. This is particularly important in cardiovascular system, where adenosine protects against endothelial dysfunction, vascular inflammation, or thrombosis. Besides enzymatic function, ADA protein mediates cell-to-cell interactions involved in lymphocyte co-stimulation or endothelial activation. Furthermore, alteration in ADA activity was demonstrated in many cardiovascular pathologies such as atherosclerosis, myocardial ischemia-reperfusion injury, hypertension, thrombosis, or diabetes. Modulation of ADA activity could be an important therapeutic target. This work provides a systematic review of ADA activity and anchoring inhibitors as well as summarizes the perspectives of their therapeutic use in cardiovascular pathologies associated with increased activity of ADA.

scholarly journals YAP Controls Endothelial Activation and Vascular Inflammation Through TRAF6

2018 ◽  
Vol 123 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Yang Lv ◽  
Kyungho Kim ◽  
Yue Sheng ◽  
Jaehyung Cho ◽  
Zhijian Qian ◽  
...  
Keyword(s):  
Vascular Inflammation ◽  
Endothelial Activation

The Effects of Angiotensin II Infusion on the Mechanical Response and Microstructural Organization of Mouse Aorta

2010 ◽  
Author(s):  
Darren Haskett ◽  
Marie Fouts ◽  
Urs Utzinger ◽  
Doug Larson ◽  
Mohamad Azhar ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Vascular Disease ◽  
Mechanical Response ◽  
Vascular Inflammation ◽  
Vascular Diseases ◽  
The United States ◽  
Matrix Remodeling ◽  
Atherosclerotic Vascular Disease ◽  
Thoracic And Abdominal ◽  
Aortic Remodeling

Vascular diseases such as aneurysm and aortic dissection account for almost 16,000 deaths in the United States annually. In both of these diseases vascular inflammation is a common pathogenic factor. Another common pathologic feature of vascular disease includes structural matrix remodeling. It is also increasingly believed that inflammation may play a key role in the formation and progression of atherosclerotic vascular disease. Angiotensin II (AngII), a potent vasopressor, is also a strong inducer of vascular inflammation and aortic remodeling in atherosclerosis-prone mice. Based on this knowledge studies have been conducted using subcutaneous AngII infusion in order to produce aortic remodeling and aneurysm formation, with acute thoracic and abdominal aortic dissections [1].

scholarly journals Structural and Functional Changes in Bosnian Family - Disappearance of the “Sofra”

2020 ◽  
Vol 3 (2) ◽  
pp. 68
Author(s):  
Amel Alić
Keyword(s):  
Social Economy ◽  
Basic Knowledge ◽  
New Paradigm ◽  
Cultural Changes ◽  
Functional Changes ◽  
Know How ◽  
Dominant Structure ◽  
Role Of Religion ◽  
Structure And Functions

The ‘sofra’ and ‘me′edeba’ are places where not only physiological needs of food consumption which are necessary for physical life are fulfilled, but they are also places where we prepare on fundamental, intellectual, emotional and social levels for participation in the society, adoption of basic knowledge about ways to satisfy own and others’ needs for safety, belonging, recognition, love, (Self) respect, and living of aesthetic and intellectual values. Before we sit at the ‘sofra’, we participate in serving of the food, and we learn to listen to and look at each other, to educate all senses by exchanging impressions and opinions about tastes. If all meanings of ‘sofra’ and ‘me’edeba’ are satisfied, we always happily go back to that place, but we also know how to transfer that knowledge to the next generation. Therefore, we learn to adopt culture through enculturation processes. The most explicit changes in dimension of adaptability and cohesion suggest that Bosnian family, besides social, economy, and political changes, passes through unprecedented and unique transformation, which could be connected to far more complex cultural changes – what we assume to be – transformation of normative / relational collectivism and individualism, increased migrations, different / changed role of religion, and a new paradigm of identity definition. In that sense, this article represents an attempt to determine in what way different custom, forms and functions of Bosnian family, above all, the dominant structure and functions, changes throughout the past three decades.

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