The vasa vasorum in diseased and nondiseased arteries

The vasa vasorum form a network of microvasculature that originate primarily in the adventitial layer of large arteries. These vessels supply oxygen and nutrients to the outer layers of the arterial wall. The expansion of the vasa vasorum to the second order is associated with neovascularization related to progression of atherosclerosis. Immunohistological analysis of human plaques from autopsied aortas have defined plaque progression and show a significant correlation with vasa vasorum neovascularization. Recent technological advances in microcomputed tomography have enabled investigation of vasa vasorum structure and function in nondiseased large arteries from pigs and dogs. Smaller mammals, particularly mice with genetic modifications that enable disease development, have been used extensively to study the vasa vasorum in diseased vessels. Despite the fact that most mouse models that are used to study atherosclerosis are unable to develop plaque to the extent found in humans, studies in both humans and mice underscore the importance of angiogenic vasa vasorum in progression of atherosclerosis. Those who have examined the vasa vasorum in occluded vessels of nondiseased pigs and dogs find that inhibition of the vasa vasorum makes the animals atheroprone. Atherosclerosis is a multifactorial disease. There is increasing evidence that factors, produced in response to changes in the arterial wall, collaborate with the vasa vasorum to enhance the disease process.

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Vascular Fluid Mechanics, the Arterial Wall, and Atherosclerosis

Journal of Biomechanical Engineering ◽

10.1115/1.2891384 ◽

1992 ◽

Vol 114 (3) ◽

pp. 274-282 ◽

Cited By ~ 321

Author(s):

R. M. Nerem

Keyword(s):

Cell Culture ◽

Blood Flow ◽

Fluid Mechanics ◽

Arterial Wall ◽

Disease Process ◽

The United States ◽

Structure And Function ◽

Medium Size ◽

Important Relationship ◽

And Function

Atherosclerosis, a disease of large- and medium-size arteries, is the chief cause of death in the United States and in most of the western world. Severe atherosclerosis interferes with blood flow; however, even in the early stages of the disease, i.e. during atherogenesis, there is believed to be an important relationship between the disease processes and the characteristics of the blood flow in the arteries. Atherogenesis involves complex cascades of interactions among many factors. Included in this are fluid mechanical factors which are believed to be a cause of the highly focal nature of the disease. From in vivo studies, there is evidence of hemodynamic influences on the endothelium, on intimal thickening, and on monocyte recruitment. In addition, cell culture studies have demonstrated the important effect of a cell’s mechanical environment on structure and function. Most of this evidence is for the endothelial cell, which is believed to be a key mediator of any hemodynamic effect, and it is now well documented that cultured endothelial monolayers, in response to a fluid flow-imposed laminar shear stress, undergo a variety of changes in structure and function. In spite of the progress in recent years, there are many areas in which further work will provide important new information. One of these is in the engineering of the cell culture environment so as to make it more physiologic. Animal studies also are essential in our efforts to understand atherogenesis, and it is clear that we need better information on the pattern of the disease and its temporal development in humans and animal models, as well as the specific underlying biologic events. Complementary to this will be in vitro model studies of arterial fluid mechanics. In addition, one can foresee an increasing role for computer modelling in our efforts to understand the pathophysiology of the atherogenic process. This includes not only computational fluid mechanics, but also modelling the pathobiologic processes taking place within the arterial wall. A key to the atherogenic process may reside in understanding how hemodynamics influences not only intimal smooth muscle cell proliferation, but also the recruitment of the monocyte/macrophage and the formation of foam cells. Finally, it will be necessary to begin to integrate our knowledge of cellular phenomena into a description of the biologic processes within the arterial wall and then to integrate this into a picture of the disease process itself.

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Scavenger Receptors as Biomarkers and Therapeutic Targets in Cardiovascular Disease

Cells ◽

10.3390/cells9112453 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2453

Author(s):

Gary A. Cuthbert ◽

Faheem Shaik ◽

Michael A. Harrison ◽

Sreenivasan Ponnambalam ◽

Shervanthi Homer-Vanniasinkam

Keyword(s):

Cardiovascular Disease ◽

Arterial Wall ◽

Arterial Disease ◽

Disease Diagnosis ◽

Structure And Function ◽

Scavenger Receptors ◽

Lipid Particles ◽

Membrane Bound ◽

And Function ◽

Progression Of Atherosclerosis

The process of atherosclerosis leads to the formation of plaques in the arterial wall, resulting in a decreased blood supply to tissues and organs and its sequelae: morbidity and mortality. A class of membrane-bound proteins termed scavenger receptors (SRs) are closely linked to the initiation and progression of atherosclerosis. Increasing interest in understanding SR structure and function has led to the idea that these proteins could provide new routes for cardiovascular disease diagnosis, management, and treatment. In this review, we consider the main classes of SRs that are implicated in arterial disease. We consider how our understanding of SR-mediated recognition of diverse ligands, including modified lipid particles, lipids, and carbohydrates, has enabled us to better target SR-linked functionality in disease. We also link clinical studies on vascular disease to our current understanding of SR biology and highlight potential areas that are relevant to cardiovascular disease management and therapy.

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Current Research Landscape of Marine-Derived Anti-Atherosclerotic Substances

Marine Drugs ◽

10.3390/md18090440 ◽

2020 ◽

Vol 18 (9) ◽

pp. 440 ◽

Cited By ~ 1

Author(s):

Qi Cao ◽

Jiarui Zhao ◽

Maochen Xing ◽

Han Xiao ◽

Qian Zhang ◽

...

Keyword(s):

Arterial Wall ◽

Low Cost ◽

Therapeutic Agents ◽

Mechanisms Of Action ◽

New Drugs ◽

Material Basis ◽

Technological Advances ◽

Rich Material ◽

Progression Of Atherosclerosis ◽

Proteins And Peptides

Atherosclerosis is a chronic disease characterized by lipid accumulation and chronic inflammation of the arterial wall, which is the pathological basis for coronary heart disease, cerebrovascular disease and thromboembolic disease. Currently, there is a lack of low-cost therapeutic agents that effectively slow the progression of atherosclerosis. Therefore, the development of new drugs is urgently needed. The research and development of marine-derived drugs have gained increasing interest from researchers across the world. Many marine organisms provide a rich material basis for the development of atherosclerotic drugs. This review focuses on the latest technological advances in the structures and mechanisms of action of marine-derived anti-atherosclerotic substances and the challenges of the application of these substances including marine polysaccharides, proteins and peptides, polyunsaturated fatty acids and small molecule compounds. Here, we describe the theoretical basis of marine biological resources in the treatment of atherosclerosis.

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Early Microvascular Dysfunction: Is the Vasa Vasorum a “Missing Link” in Insulin Resistance and Atherosclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms22147574 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7574

Author(s):

Jeanette Owusu ◽

Eugene Barrett

Keyword(s):

Insulin Resistance ◽

Arterial Wall ◽

Microvascular Dysfunction ◽

Structure And Function ◽

Vasa Vasorum ◽

Atherosclerotic Vascular Disease ◽

Potential Impact ◽

Atherosclerosis Development ◽

And Function ◽

The Impact

The arterial vasa vasorum is a specialized microvasculature that provides critical perfusion required for the health of the arterial wall, and is increasingly recognized to play a central role in atherogenesis. Cardio-metabolic disease (CMD) (including hypertension, metabolic syndrome, obesity, diabetes, and pre-diabetes) is associated with insulin resistance, and characteristically injures the microvasculature in multiple tissues, (e.g., the eye, kidney, muscle, and heart). CMD also increases the risk for atherosclerotic vascular disease. Despite this, the impact of CMD on vasa vasorum structure and function has been little studied. Here we review emerging information on the early impact of CMD on the microvasculature in multiple tissues and consider the potential impact on atherosclerosis development and progression, if vasa vasorum is similarly affected.

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Contribution to the pathogenesis of radiation-induced injury to large arteries

The Journal of Laryngology & Otology ◽

10.1017/s0022215100139167 ◽

1997 ◽

Vol 111 (10) ◽

pp. 988-990 ◽

Cited By ~ 45

Author(s):

Nina Zidar ◽

Dušan Ferluga ◽

Asta Hvala ◽

Mara Popovć ◽

Erika Šoba

Keyword(s):

Arterial Wall ◽

Internal Carotid ◽

Experimental Studies ◽

Arterial Injury ◽

Vasa Vasorum ◽

Necrotizing Vasculitis ◽

Cervical Lymph Nodes ◽

Large Arteries ◽

Radiation Induced ◽

Late Stages

AbstractWe report a case of a 35-year-old man who died of a brain infarct 20 months after radiotherapy for carcinoma of the tonsil with metastases to the cervical lymph nodes. Histology revealed mild atherosclerosis, necrotizing vasculitis, and occlusive thrombosis of the internal carotid artery. Significant changes were observed in the vasa vasorum: swelling and detachment of the endothelium, subendothelial oedema, hyaline change, fibrinoid necrosis of the vessel walls with mononuclear cellular infiltration, accompanied by focal haemorrhages and chronic inflammation in the periadventitial soft tissue. We believe that these changes of the vasa vasorum and necrotizing vasculitis are causally related and that vasculitis represents focal ischaemic necroses with inflammatory reaction. Our findings support the hypothesis, based on experimental studies, that injury to the vasa vasorum is an important mechanism in the development of radiation-induced vasculopathy of large arteries. They also suggest an evolution of the injury to the vasa vasorum and periadventitial tissue from the early lesions described in our patient, to late stages resulting in dense periadventitial fibrosis as reported previously. We suggest that injury to the vasa vasorum and the consequent ischaemic lesions of the arterial wall are morphological features distinguishing radiation-induced arterial injury from spontaneous atherosclerosis.

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Morphological and Biochemical Features Affecting the Antithrombotic Properties of the Aorta in Adult Rabbits and Rabbit Pups

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615116 ◽

1998 ◽

Vol 79 (05) ◽

pp. 1034-1040 ◽

Cited By ~ 17

Author(s):

E. Nitschmann ◽

L. Berry ◽

S. Bridge ◽

M. W. C. Hatton ◽

M. Richardson ◽

...

Keyword(s):

Electron Microscopy ◽

Gel Electrophoresis ◽

Arterial Wall ◽

Structure And Function ◽

Wall Structure ◽

Matrix Structure ◽

Antithrombotic Activity ◽

Antithrombin Activity ◽

And Function ◽

Biochemical Features

SummaryWe hypothesised that there are important physiologic differences in arterial wall structure and function with respect to antithrombotic activity in the very young (pre-puberty) compared to adults. Electron microscopy, gel electrophoresis, and activity assays were used to examine differences in aorta structure and function comparing prepubertal rabbits (pups) to adult rabbits. Differences in endothelial function, extracellular matrix structure, proteoglycan (PG) distribution and glycosaminoglycan (GAG) content and function were shown. In both intima and media, total PG, chondroitin sulfate (CS) PG and heparan sulfate (HS) PG content were significantly increased in pups compared to adult rabbits. These findings corresponded to increased concentrations by mass analyses of CS GAG and DS GAG in aortas from pups. There was also a significant increase in antithrombin activity in pups due to HS GAG. In conclusion, differences in both structure and antithrombin activity of aortas from pups compared to adult rabbits suggest that young arteries may have greater antithrombotic potential that is, at least in part, related to increased HS GAG.

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Wnt Signaling in Vascular Calcification

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.708470 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kaylee Bundy ◽

Jada Boone ◽

C. LaShan Simpson

Keyword(s):

Cardiovascular Disease ◽

Wnt Signaling ◽

Signaling Pathway ◽

Vascular Calcification ◽

Arterial Wall ◽

Wnt Signaling Pathway ◽

Phenotypic Switch ◽

Wnt Ligands ◽

And Function ◽

Canonical Wnt

Cardiovascular disease is a worldwide epidemic and considered the leading cause of death globally. Due to its high mortality rates, it is imperative to study the underlying causes and mechanisms of the disease. Vascular calcification, or the buildup of hydroxyapatite within the arterial wall, is one of the greatest contributors to cardiovascular disease. Medial vascular calcification is a predictor of cardiovascular events such as, but not limited to, hypertension, stiffness, and even heart failure. Vascular smooth muscle cells (VSMCs), which line the arterial wall and function to maintain blood pressure, are hypothesized to undergo a phenotypic switch into bone-forming cells during calcification, mimicking the manner by which mesenchymal stem cells differentiate into osteoblast cells throughout osteogenesis. RunX2, a transcription factor necessary for osteoblast differentiation and a target gene of the Wnt signaling pathway, has also shown to be upregulated when calcification is present, implicating that the Wnt cascade may be a key player in the transdifferentiation of VSMCs. It is important to note that the phenotypic switch of VSMCs from a healthy, contractile state to a proliferative, synthetic state is necessary in response to the vascular injury surrounding calcification. The lingering question, however, is if VSMCs acquire this synthetic phenotype through the Wnt pathway, how and why does this signaling occur? This review seeks to highlight the potential role of the canonical Wnt signaling pathway within vascular calcification based on several studies and further discuss the Wnt ligands that specifically aid in VSMC transdifferentiation.

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Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.759735 ◽

2022 ◽

Vol 8 ◽

Author(s):

Shuangyue Li ◽

Georgios Kararigas

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Microbial Composition ◽

Biological Sex ◽

Technological Advances ◽

Host Health ◽

Health And Disease ◽

And Function ◽

Insight Into

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

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Physical factors in arterial ageing

Oxford Textbook of Geriatric Medicine ◽

10.1093/med/9780198701590.003.0097 ◽

2017 ◽

pp. 743-748

Author(s):

Junichiro Hashimoto ◽

Michael F. O’Rourke

Keyword(s):

Pressure Wave ◽

Pressure Control ◽

Cardiac Contraction ◽

Physical Factors ◽

Large Arteries ◽

Function Change ◽

Pulsatile Pressure ◽

Arterial Structure ◽

Optimal Blood Pressure ◽

And Function

Arterial structure and function change progressively with advancing age. Owing to long-lasting repetitive stretch with intermittent cardiac contraction, elastic fibres in the tunica media of large arteries progressively degenerate and are replaced by collagenous fibres. Such degeneration causes elastic arteries to stiffen and dilate. Stiffening of the large arteries not only increases amplitude of the incident pressure wave but also hastens the return of the reflected pressure wave, thereby widening the pulse pressure in the central aorta. This widening increases the cardiac afterload during systole, while it decreases coronary flow during diastole, thus predisposing to heart failure and coronary ischaemia. Also, the excessive pulsatile pressure is transmitted deeply into the renal and cerebral microvasculature causing microalbuminuria and lacunar infarction. Although arterial ageing is considered an inevitable and irreversible process, it can be delayed through optimal blood pressure control.

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Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms21228729 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8729 ◽

Cited By ~ 1

Author(s):

Chih-Fan Yeh ◽

Ying-Hsien Chen ◽

Sheng-Fu Liu ◽

Hsien-Li Kao ◽

Ming-Shiang Wu ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Cytokine Production ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Inflammasome Activation ◽

Host Immune System ◽

Gut Permeability ◽

And Function ◽

Progression Of Atherosclerosis

Inflammation is the key for the initiation and progression of atherosclerosis. Accumulating evidence has revealed that an altered gut microbiome (dysbiosis) triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis. There have been some microbiome-relevant pro-inflammatory mechanisms proposed to link the relationships between dysbiosis and atherosclerosis such as gut permeability disruption, trigger of innate immunity from lipopolysaccharide (LPS), and generation of proatherogenic metabolites, such as trimethylamine N-oxide (TMAO). Meanwhile, immune responses, such as inflammasome activation and cytokine production, could reshape both composition and function of the microbiota. In fact, the immune system delicately modulates the interplay between microbiota and atherogenesis. Recent clinical trials have suggested the potential of immunomodulation as a treatment strategy of atherosclerosis. Here in this review, we present current knowledge regarding to the roles of microbiota in contributing atherosclerotic pathogenesis and highlight translational perspectives by discussing the mutual interplay between microbiota and immune system on atherogenesis.

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