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Histopathology Nov 2023Giant cell arteritis (GCA) is a systemic vasculitis affecting medium and large arteries in patients aged over 50 years. Involvement of temporal arteries (TA) can lead...
AIMS
Giant cell arteritis (GCA) is a systemic vasculitis affecting medium and large arteries in patients aged over 50 years. Involvement of temporal arteries (TA) can lead to complications such as blindness and stroke. While the diagnostic gold standard is temporal artery biopsy (TAB), comorbidities and age-related changes can make interpretation of such specimens difficult. This study aims to establish a baseline of TA changes in subjects without GCA to facilitate the interpretation of TAB.
METHODS AND RESULTS
Bilateral TA specimens were collected from 100 consecutive eligible postmortem examinations. Subjects were divided into four age groups and specimens semiquantitatively evaluated for eccentric intimal fibroplasia, disruption and calcification of the internal elastic lamina (IEL), medial attenuation and degree of lymphocytic inflammation of the peri-adventitia, adventitia, media and intima. The individual scores of intimal fibroplasia, IEL disruption and medial attenuation were added to yield a 'combined score (CS)'. Seventy-eight 78 decedents were included in the final analysis following exclusion of 22 individuals for either lack of clinical information or inability to collect TA tissue. A total of 128 temporal artery specimens (50 bilateral from individual decedents, 28 unilateral) were available for examination. Intimal proliferation, IEL loss, IEL calcification and CS increased with age in a statistically significant fashion. Comparison of the oldest age group with the others showed statistically significant differences, although this was not uniformly preserved in comparison between the three youngest groups.
CONCLUSION
Senescent arterial changes and healed GCA exhibit histological similarity and such changes increase proportionally with age. The CS demonstrates significant association with age overall and represents a potential avenue for development to 'normalise' TA biopsies from older individuals.
Topics: Humans; Middle Aged; Temporal Arteries; Giant Cell Arteritis; Biopsy; Retrospective Studies
PubMed: 37551446
DOI: 10.1111/his.15019 -
European Cardiology 2023Recent clinical trials have highlighted that percutaneous coronary intervention in patients with stable angina provides limited additional benefits on top of optimal... (Review)
Review
Recent clinical trials have highlighted that percutaneous coronary intervention in patients with stable angina provides limited additional benefits on top of optimal medical therapy. This has led to much more attention being paid to coronary vasomotion abnormalities regardless of obstructive or non-obstructive arterial segments. Coronary vasomotion is regulated by multiple mechanisms that include the endothelium, vascular smooth muscle cells (VSMCs), myocardial metabolic demand, autonomic nervous system and inflammation. Over the years, several animal models have been developed to explore the central mechanism of coronary artery spasm. This review summarises the landmark studies on the mechanisms of coronary vasospasm demonstrating the central role of Rho-kinase as a molecular switch of VSMC hypercontraction and the important role of coronary adventitial inflammation for Rho-kinase upregulation in VSMCs.
PubMed: 37456775
DOI: 10.15420/ecr.2022.55 -
Neurosurgical Focus Jul 2019Wall shear stress, the frictional force of blood flow tangential to an artery lumen, has been demonstrated in multiple studies to influence aneurysm formation and risk... (Review)
Review
Wall shear stress, the frictional force of blood flow tangential to an artery lumen, has been demonstrated in multiple studies to influence aneurysm formation and risk of rupture. In this article, the authors review the ways in which shear stress may influence aneurysm growth and rupture through changes in the vessel wall endothelial cells, smooth-muscle cells, and surrounding adventitia, and they discuss shear stress-induced pathways through which these changes occur.
Topics: Aneurysm; Animals; Blood Vessels; Endothelial Cells; Endothelium, Vascular; Humans; Intracranial Aneurysm; Stress, Physiological
PubMed: 31261124
DOI: 10.3171/2019.4.FOCUS19225 -
Current Opinion in Hematology May 2020The well recognized plasticity and diversity, typical of monocytes and macrophages have recently been expanded by the knowledge that additional macrophage lineages... (Review)
Review
PURPOSE OF REVIEW
The well recognized plasticity and diversity, typical of monocytes and macrophages have recently been expanded by the knowledge that additional macrophage lineages originated directly from embryonic progenitors, populate and establish residency in all tissues examined so far. This review aims to summarize our current understanding on the diversity of monocyte/macrophage subtypes associated with the vasculature, their specific origins, and nature of their cross-talk with the endothelium.
RECENT FINDINGS
Taking stock of the many interactions between the endothelium and monocytes/macrophages reveals a far more intricate and ever-growing depth. In addition to circulating and surveilling the endothelium, monocytes can specifically be differentiated into patrolling cells that crawl on the surface of the endothelium and promote homeostasis. The conversion of classical to patrolling is endothelium-dependent uncovering an important functional link. In addition to patrolling cells, the endothelium also recruits and harbor an intimal-resident myeloid population that resides in the tunica intima in the absence of pathological insults. Moreover, the adventitia is populated with resident macrophages that support blood vessel integrity and prevent fibrosis.
SUMMARY
The last few years have witnessed a significant expansion in our knowledge of the many subtypes of monocytes and macrophages and their corresponding functional interactions with the vascular wall. In addition to surveying the endothelium for opportunities of diapedeses, monocyte and macrophages take residence in both the intima (as patrolling or resident) and in the adventitia. Their contributions to vascular function are broad and critical to homeostasis, regeneration, and expansion.
Topics: Animals; Cell Communication; Endothelial Cells; Endothelium, Vascular; Humans; Macrophages; Monocytes
PubMed: 32167947
DOI: 10.1097/MOH.0000000000000573 -
Methods in Molecular Biology (Clifton,... 2022Recent advances in cardiovascular research have led to a more comprehensive understanding of molecular mechanisms of atherosclerosis. It has become apparent that the...
Recent advances in cardiovascular research have led to a more comprehensive understanding of molecular mechanisms of atherosclerosis. It has become apparent that the disease involves three layers of the arterial wall: the intima, the media, and a connective tissue coat termed the adventitia. It is also now appreciated that arteries are surrounded by adipose and neuronal tissues. In addition, adjacent to and within the adventitia, arteries are embedded in a loose connective tissue containing blood vessels (vasa vasora) and lymph vessels, artery-draining lymph nodes and components of the peripheral nervous system, including periarterial nerves and ganglia. During atherogenesis, each of these tissues undergoes marked structural and cellular alterations. We propose that a better understanding of these cell-cell and cell-tissue interactions may considerably advance our understanding of cardiovascular disease pathogenesis. Methods to acquire subcellular optical access to the intact tissues surrounding healthy and diseased arteries are urgently needed to achieve these aims. Tissue clearing is a landmark next-generation, three-dimensional (3D) microscopy technique that allows to image large-scale hitherto inaccessible intact deep tissue compartments. It allows for detailed reconstructions of arteries by a combination of labelling, clearing, advanced microscopies and other imaging and data-analysis tools. Here, we describe two distinct tissue clearing protocols; solvent-based modified three-dimensional imaging of solvent-cleared organs (3DISCO) clearing and another using aqueous-based 2,2'-thiodiethanol (TDE) clearing, both of which complement each other.
Topics: Arteries; Atherosclerosis; Humans; Imaging, Three-Dimensional; Microscopy
PubMed: 35237999
DOI: 10.1007/978-1-0716-1924-7_45 -
Arteriosclerosis, Thrombosis, and... Nov 2020Atherosclerosis is orchestrated by complex interactions between vascular and inflammatory cells. Traditionally, it has been considered to be an intimal inflammatory... (Review)
Review
Atherosclerosis is orchestrated by complex interactions between vascular and inflammatory cells. Traditionally, it has been considered to be an intimal inflammatory disease, characterized by endothelial dysfunction, inflammatory cell recruitment, lipid oxidation, and foam cell formation. This inside-out signaling paradigm has been accepted as dogma for many years, despite the fact that inflammatory cells are far more prevalent in the adventitia compared with the intima. For decades, the origin of adventitial inflammation in atherosclerosis was unknown. The fact that these inflammatory cells were observed to cluster at the margin of perivascular adipose tissues-a unique and highly inflammatory adipose depot that surrounds most atherosclerosis-prone blood vessels-has stimulated interest in perivascular adipose tissue-mediated outside-in signaling in vascular pathophysiology, including atherosclerosis. The phenotype of perivascular adipocytes underlies the functional characteristics of this depot, including its role in adventitial inflammatory cell recruitment, trafficking to the intima via the vasa vasorum, and atherosclerosis perturbation. This review is focused on emerging concepts pertaining to outside-in signaling in atherosclerosis driven by dysfunctional perivascular adipose tissues during diet-induced obesity and recent strategies for atherosclerosis prediction and prognostication based upon this hypothesis.
Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Atherosclerosis; Blood Vessels; Cell Communication; Humans; Inflammation; Inflammation Mediators; Plaque, Atherosclerotic; Signal Transduction
PubMed: 32878476
DOI: 10.1161/ATVBAHA.120.312470 -
F1000Research 2020Urothelial pediatric neoplasms are relatively rare. Papillary urothelial neoplasms of low malignant potential (PUNLMPs) and rhabdomyosarcoma (RMS) are the most common... (Review)
Review
Urothelial pediatric neoplasms are relatively rare. Papillary urothelial neoplasms of low malignant potential (PUNLMPs) and rhabdomyosarcoma (RMS) are the most common bladder malignancies in the pediatric population. Clinical presentation encompasses macroscopic hematuria or lower urinary tract symptoms (or both) or is detected incidentally at imaging. Tumors arising from the bladder can originate from any of its four histological layers (urothelium, lamina propria, detrusor, and adventitia) and are divided into tumors that have an epithelial origin (arising from the urothelium) and those that have a non-epithelial origin (mesenchymal neoplasms). RMS is the most common malignant tumor of the urinary bladder in children younger than 10 years. Deriving from the embryonic mesenchymal cell, the histopathologic subtypes of RMS are embryonal RMS (>90%) and alveolar histology (<10%). Pre-treatment imaging should be carried out by computed tomography (CT) or at present is more likely with magnetic resonance imaging of the pelvis. Chest CT and bone scintigraphy are used to screen for metastases. In selected cases, a positron emission tomography scan may be recommended to evaluate suspicious lesions. The current prognostic classification considers age, histologic subtype, tumor site, size, and extent (nodal or distant metastases). Staging is based on pre-operative findings, group is based on intra-operative findings and pathology, and risk stratification is derived from both stage and group data. Pre-operative chemotherapy is the most common first-line intervention for bladder/prostate RMS, before surgery or radiation therapy. Collaborative groups such as the Soft Tissue Sarcoma Committee of the Children's Oncology Group and the European Pediatric Soft Tissue Sarcoma Study Group endorse this therapy. PUNLMPs are generally solitary, small (1-2 cm), non-invasive lesions that do not metastasize. Therapy is usually limited to a transurethral resection of the bladder tumor. About 35% are recurrent and around 10% of them increase in size if they are not treated.
Topics: Child; Humans; Male; Prognosis; Prostatic Neoplasms; Rhabdomyosarcoma; Urinary Bladder Neoplasms
PubMed: 32148770
DOI: 10.12688/f1000research.19396.1 -
Zeitschrift Fur Rheumatologie Aug 2020Large vessel vasculitides comprise two distinct entities, giant cell arteritis (GCA) and Takayasu arteritis (TAK). GCA is the most common vasculitis in central Europe,... (Review)
Review
Large vessel vasculitides comprise two distinct entities, giant cell arteritis (GCA) and Takayasu arteritis (TAK). GCA is the most common vasculitis in central Europe, becoming manifested at an age over 50 years. In contrast, the much rarer TAK affects almost exclusively young adults and mostly women. Both vasculitides are granulomatous arteritides affecting mainly the aorta and its major arterial branches. GCA and TAK are associated with different major histocompatibility complex genes. Infections possibly play a role in the initiation of large vessel vasculitides. Activation of dendritic cells in the adventitia induces chemokine and cytokine-mediated recruitment and maturation of T‑helper (Th)1 and Th17 cells and macrophages producing cytokines, growth factors and matrix metalloproteinases. In GCA, CD4+ T‑helper cells and macrophages are predominantly found in the inflammatory infiltrate. In TAK, the infiltrate also contains cytotoxic CD8+ T‑cells and γδ T‑cells. This could indicate different antigenic triggers in GCA and TAK. Inflammatory infiltration with T‑cells and macrophages and activation of myofibroblasts and smooth muscular cells induce vascular remodeling with intimal hyperplasia and destruction of the media. Remodeling is histologically characterized by progressive arterial wall fibrosis, vascular stenosis and obstruction. In summary, GCA and TAK represent two different entities with a distinct human leukocyte antigen (HLA) and potentially etiopathogenetic background. Clinically, inflammation-related general symptoms and signs of ischemia are encountered, accompanied by increased levels of serological markers of inflammation.
Topics: Adult; Cytokines; Europe; Female; Giant Cell Arteritis; Humans; Macrophages; Male; Takayasu Arteritis; Young Adult
PubMed: 32430566
DOI: 10.1007/s00393-020-00809-z -
Cells May 2021In recent years, lymphatic vessels have received increasing attention and our understanding of their development and functional roles in health and diseases has greatly... (Review)
Review
In recent years, lymphatic vessels have received increasing attention and our understanding of their development and functional roles in health and diseases has greatly improved. It has become clear that lymphatic vessels are critically involved in acute and chronic inflammation and its resolution by supporting the transport of immune cells, fluid, and macromolecules. As we will discuss in this review, the involvement of lymphatic vessels has been uncovered in atherosclerosis, a chronic inflammatory disease of medium- and large-sized arteries causing deadly cardiovascular complications worldwide. The progression of atherosclerosis is associated with morphological and functional alterations in lymphatic vessels draining the diseased artery. These defects in the lymphatic vasculature impact the inflammatory response in atherosclerosis by affecting immune cell trafficking, lymphoid neogenesis, and clearance of macromolecules in the arterial wall. Based on these new findings, we propose that targeting lymphatic function could be considered in conjunction with existing drugs as a treatment option for atherosclerosis.
Topics: Arteries; Atherosclerosis; Culture Media; Heart Diseases; Humans; Leukocytes; Lymphatic Vessels
PubMed: 34072313
DOI: 10.3390/cells10061344