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Nature Reviews. Cardiology Jul 2019Atherosclerosis is a lipid-driven inflammatory disease of the arterial intima in which the balance of pro-inflammatory and inflammation-resolving mechanisms dictates the... (Review)
Review
Atherosclerosis is a lipid-driven inflammatory disease of the arterial intima in which the balance of pro-inflammatory and inflammation-resolving mechanisms dictates the final clinical outcome. Intimal infiltration and modification of plasma-derived lipoproteins and their uptake mainly by macrophages, with ensuing formation of lipid-filled foam cells, initiate atherosclerotic lesion formation, and deficient efferocytotic removal of apoptotic cells and foam cells sustains lesion progression. Defective efferocytosis, as a sign of inadequate inflammation resolution, leads to accumulation of secondarily necrotic macrophages and foam cells and the formation of an advanced lesion with a necrotic lipid core, indicative of plaque vulnerability. Resolution of inflammation is mediated by specialized pro-resolving lipid mediators derived from omega-3 fatty acids or arachidonic acid and by relevant proteins and signalling gaseous molecules. One of the major effects of inflammation resolution mediators is phenotypic conversion of pro-inflammatory macrophages into macrophages that suppress inflammation and promote healing. In advanced atherosclerotic lesions, the ratio between specialized pro-resolving mediators and pro-inflammatory lipids (in particular leukotrienes) is strikingly low, providing a molecular explanation for the defective inflammation resolution features of these lesions. In this Review, we discuss the mechanisms of the formation of clinically dangerous atherosclerotic lesions and the potential of pro-resolving mediator therapy to inhibit this process.
Topics: Animals; Apoptosis; Atherosclerosis; Humans; Inflammasomes; Inflammation; Lipid Metabolism; Lipoproteins; Macrophages; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction; Tunica Intima
PubMed: 30846875
DOI: 10.1038/s41569-019-0169-2 -
Bosnian Journal of Basic Medical... Feb 2020Atherosclerosis is a chronic inflammatory disease of arteries and it affects the structure and function of all three layers of the coronary artery wall. Current theories... (Review)
Review
Atherosclerosis is a chronic inflammatory disease of arteries and it affects the structure and function of all three layers of the coronary artery wall. Current theories suggest that the dysfunction of endothelial cells is one of the initial steps in the development of atherosclerosis. The view that the tunica intima normally consists of a single layer of endothelial cells attached to the subendothelial layer and internal elastic membrane has been questioned in recent years. The structure of intima changes with age and it becomes multilayered due to migration of smooth muscle cells from the media to intima. At this stage, the migration and proliferation of smooth muscle cells do not cause pathological changes in the intima. The multilayering of intima is classically considered to be an important stage in the development of atherosclerosis, but in fact atherosclerotic plaques develop only focally due to the interplay of various processes that involve the resident and invading inflammatory cells. The tunica media consists of multiple layers of smooth muscle cells that produce the extracellular matrix, and this layer normally does not contain microvessels. During the development of atherosclerosis, the microvessels from the tunica adventitia or from the lumen may penetrate thickened media to provide nutrition and oxygenation. According to some theories, the endothelial dysfunction of these nutritive vessels may significantly contribute to the atherosclerosis of coronary arteries. The adventitia contains fibroblasts, progenitor cells, immune cells, microvessels, and adrenergic nerves. The degree of inflammatory cell infiltration into the adventitia, which can lead to the formation of tertiary lymphoid organs, correlates with the severity of atherosclerotic plaques. Coronary arteries are surrounded by perivascular adipose tissue that also participates in the atherosclerotic process.
Topics: Adventitia; Coronary Artery Disease; Humans; Plaque, Atherosclerotic; Tunica Intima; Tunica Media
PubMed: 31465719
DOI: 10.17305/bjbms.2019.4320 -
Arteriosclerosis, Thrombosis, and... Sep 2021Endothelial-to-mesenchymal transition is a dynamic process in which endothelial cells suppress constituent endothelial properties and take on mesenchymal cell behaviors.... (Review)
Review
Endothelial-to-mesenchymal transition is a dynamic process in which endothelial cells suppress constituent endothelial properties and take on mesenchymal cell behaviors. To begin the process, endothelial cells loosen their cell-cell junctions, degrade the basement membrane, and migrate out into the perivascular surroundings. These initial endothelial behaviors reflect a transient modulation of cellular phenotype, that is, a phenotypic modulation, that is sometimes referred to as partial endothelial-to-mesenchymal transition. Loosening of endothelial junctions and migration are also seen in inflammatory and angiogenic settings such that endothelial cells initiating endothelial-to-mesenchymal transition have overlapping behaviors and gene expression with endothelial cells responding to inflammatory signals or sprouting to form new blood vessels. Reduced endothelial junctions increase permeability, which facilitates leukocyte trafficking, whereas endothelial migration precedes angiogenic sprouting and neovascularization; both endothelial barriers and quiescence are restored as inflammatory and angiogenic stimuli subside. Complete endothelial-to-mesenchymal transition proceeds beyond phenotypic modulation such that mesenchymal characteristics become prominent and endothelial functions diminish. In proadaptive, regenerative settings the new mesenchymal cells produce extracellular matrix and contribute to tissue integrity whereas in maladaptive, pathologic settings the new mesenchymal cells become fibrotic, overproducing matrix to cause tissue stiffness, which eventually impacts function. Here we will review what is known about how TGF (transforming growth factor) β influences this continuum from junctional loosening to cellular migration and its relevance to cardiovascular diseases.
Topics: Animals; Cardiovascular Diseases; Cell Movement; Endothelial Cells; Endothelium, Vascular; Epithelial-Mesenchymal Transition; Humans; Permeability; Phenotype; Signal Transduction
PubMed: 34196216
DOI: 10.1161/ATVBAHA.121.313788 -
European Heart Journal Jun 2014Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of... (Review)
Review
Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns of VC often coincide and occur in patients with type II diabetes, chronic kidney disease, and other less frequent disorders; VCs are also typical in senile degeneration. In this article, we review the current state of knowledge about the pathology, molecular biology, and nosology of VCm, expand on potential mechanisms responsible for poor prognosis, and expose some of the directions for future research in this area.
Topics: Adult; Arteriosclerosis; Biomarkers; Calcium-Binding Proteins; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Hyperphosphatemia; Male; Monckeberg Medial Calcific Sclerosis; Phosphates; Prognosis; Renal Insufficiency, Chronic; Terminology as Topic; Tunica Intima; Tunica Media; Vascular Calcification
PubMed: 24740885
DOI: 10.1093/eurheartj/ehu163 -
Science (New York, N.Y.) Oct 2016Advanced atherosclerotic lesions contain senescent cells, but the role of these cells in atherogenesis remains unclear. Using transgenic and pharmacological approaches...
Advanced atherosclerotic lesions contain senescent cells, but the role of these cells in atherogenesis remains unclear. Using transgenic and pharmacological approaches to eliminate senescent cells in atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr) mice, we show that these cells are detrimental throughout disease pathogenesis. We find that foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis, where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. Together, these results demonstrate that senescent cells are key drivers of atheroma formation and maturation and suggest that selective clearance of these cells by senolytic agents holds promise for the treatment of atherosclerosis.
Topics: Animals; Atherosclerosis; Cellular Senescence; Chemokines; Cyclin-Dependent Kinase Inhibitor p16; Cytokines; Foam Cells; Mice; Mice, Transgenic; Plaque, Atherosclerotic; Receptors, LDL; Tunica Intima
PubMed: 27789842
DOI: 10.1126/science.aaf6659 -
Trends in Cell Biology Jan 2024Pericytes are known as the mural cells in small-caliber vessels that interact closely with the endothelium. Pericytes play a key role in vasculature formation and... (Review)
Review
Pericytes are known as the mural cells in small-caliber vessels that interact closely with the endothelium. Pericytes play a key role in vasculature formation and homeostasis, and when dysfunctional contribute to vasculature-related diseases such as diabetic retinopathy and neurodegenerative conditions. In addition, significant extravascular roles of pathological pericytes are being discovered with relevant implications for cancer and fibrosis. Pericyte research is challenged by the lack of consistent molecular markers and clear discrimination criteria versus other (mural) cells. However, advances in single-cell approaches are uncovering and clarifying mural cell identities, biological functions, and ontogeny across organs. We discuss the latest developments in pericyte pathobiology to inform future research directions and potential outcomes.
Topics: Humans; Pericytes; Biomarkers; Endothelium, Vascular; Homeostasis
PubMed: 37474376
DOI: 10.1016/j.tcb.2023.06.001 -
Journal of the American College of... May 2020Medium-sized and large arteries consist of 3 layers: the tunica intima, tunica media, and tunica adventitia. The tunica media accounts for the bulk of the vessel wall... (Review)
Review
Medium-sized and large arteries consist of 3 layers: the tunica intima, tunica media, and tunica adventitia. The tunica media accounts for the bulk of the vessel wall and is the chief determinant of mechanical compliance. It is primarily composed of circumferentially arranged layers of vascular smooth muscle cells that are separated by concentrically arranged elastic lamellae; a form of extracellular matrix (ECM). The tunica media is separated from the tunica intima and tunica adventitia, the innermost and outermost layers, respectively, by the internal and external elastic laminae. This second part of a 4-part JACC Focus Seminar discusses the contributions of the ECM to vascular homeostasis and pathology. Advances in genetics and proteomics approaches have fostered significant progress in our understanding of vascular ECM. This review highlights the important role of the ECM in vascular disease and the prospect of translating these discoveries into clinical disease biomarkers and potential future therapies.
Topics: Animals; Cardiology; Endothelium, Vascular; Extracellular Matrix; Humans; Muscle, Smooth, Vascular; Vascular Diseases
PubMed: 32354385
DOI: 10.1016/j.jacc.2020.03.018 -
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 -
Tissue Barriers 2016The brain microvascular network is comprised of capillaries, arterioles and venules, all of which retain - although to a different extent - blood-brain barrier (BBB)... (Review)
Review
The brain microvascular network is comprised of capillaries, arterioles and venules, all of which retain - although to a different extent - blood-brain barrier (BBB) properties. Capillaries constitute the largest and tightest microvasculature. In contrast, venules have a looser junctional arrangement, while arterioles have a lower expression of P-gp. Development and maintenance of the BBB depends on the interaction of cerebral endothelial cells with pericytes and astrocytes, which are all heterogeneous in different regions of the central nervous system. At the level of circumventricular organs microvessels are permeable, containing fenestrations and discontinuous tight junctions. In addition, the blood-spinal cord barrier - where the number of pericytes is lower and expression of junctional proteins is reduced - is also more permeable than the BBB. However, much less is known about the cellular, molecular and functional differences among other regions of the brain. This review summarizes our current knowledge on the heterogeneity of the brain microvasculature.
Topics: Animals; Astrocytes; Blood-Brain Barrier; Capillary Permeability; Endothelium, Vascular; Humans; Pericytes
PubMed: 27141424
DOI: 10.1080/21688370.2016.1143544 -
The Journal of Thoracic and... Aug 2019
Topics: Aortic Dissection; Aortic Diseases; Dilatation; Humans; Replantation; Tunica Intima
PubMed: 30446278
DOI: 10.1016/j.jtcvs.2018.10.019