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Nature Sep 2000Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. In westernized societies, it is the underlying cause of about 50% of... (Review)
Review
Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. In westernized societies, it is the underlying cause of about 50% of all deaths. Epidemiological studies have revealed several important environmental and genetic risk factors associated with atherosclerosis. Progress in defining the cellular and molecular interactions involved, however, has been hindered by the disease's aetiological complexity. Over the past decade, the availability of new investigative tools, including genetically modified mouse models of disease, has resulted in a clearer understanding of the molecular mechanisms that connect altered cholesterol metabolism and other risk factors to the development of atherosclerotic plaque. It is now clear that atherosclerosis is not simply an inevitable degenerative consequence of ageing, but rather a chronic inflammatory condition that can be converted into an acute clinical event by plaque rupture and thrombosis.
Topics: Animals; Arteriosclerosis; Coronary Disease; Humans; Risk Assessment
PubMed: 11001066
DOI: 10.1038/35025203 -
Arteriosclerosis, Thrombosis, and... May 2020
Topics: Animals; Arteries; Arteriosclerosis; Disease Progression; Genetic Predisposition to Disease; Humans; Phenotype; Plaque, Atherosclerotic; Risk Factors; Vascular Remodeling; Vascular Stiffness
PubMed: 32320295
DOI: 10.1161/ATVBAHA.120.314208 -
Journal of Atherosclerosis and... Mar 2022Iron is an important element for life; however, intracellular labile iron overload can lead to the generation of reactive oxygen species and cellular damage. Although... (Review)
Review
Iron is an important element for life; however, intracellular labile iron overload can lead to the generation of reactive oxygen species and cellular damage. Although iron is mainly utilized for heme synthesis and is incorporated into hemoglobin, body iron status is often implicated in the pathogenesis of cardiovascular diseases. In a cell, iron is used for basic processes such as cell growth, maintenance, and repair. Thus, iron is considered to be involved in the pathogenesis of arteriosclerosis. In fact, clinical and experimental studies have shown an association between iron and arteriosclerosis. These data suggest the crosstalk between iron and arteriosclerosis. However, iron metabolism in arteriosclerosis is often complicated, and the systemic and cellular mechanisms of iron homeostasis in arteriosclerosis remain completely unsolved. Thus, in this review, we aimed to examine the role of iron in arteriosclerosis.
Topics: Animals; Arteriosclerosis; Homeostasis; Humans; Iron Overload; Oxidative Stress; Reactive Oxygen Species
PubMed: 34421089
DOI: 10.5551/jat.RV17060 -
Journal of Atherosclerosis and... Mar 2021During the evolution of skeletons, terrestrial vertebrates acquired strong bones made of calcium-phosphate. By keeping the extracellular fluid in a supersaturated... (Review)
Review
During the evolution of skeletons, terrestrial vertebrates acquired strong bones made of calcium-phosphate. By keeping the extracellular fluid in a supersaturated condition regarding calcium and phosphate ions, they created the bone when and where they wanted simply by providing a cue for precipitation. To secure this strategy, they acquired a novel endocrine system to strictly control the extracellular phosphate concentration. In response to phosphate intake, fibroblast growth factor-23 (FGF23) is secreted from the bone and acts on the kidney through binding to its receptor Klotho to increase urinary phosphate excretion, thereby maintaining phosphate homeostasis. The FGF23-Klotho endocrine system, when disrupted in mice, results in hyperphosphatemia and vascular calcification. Besides, mice lacking Klotho or FGF23 suffer from complex aging-like phenotypes, which are alleviated by placing them on a low- phosphate diet, indicating that phosphate is primarily responsible for the accelerated aging. Phosphate acquires the ability to induce cell damage and inflammation when precipitated with calcium. In the blood, calcium-phosphate crystals are adsorbed by serum protein fetuin-A and prevented from growing into large precipitates. Consequently, nanoparticles that comprised calcium-phosphate crystals and fetuin-A, termed calciprotein particles (CPPs), are generated and dispersed as colloids. CPPs increase in the blood with an increase in serum phosphate and age. Circulating CPP levels correlate positively with vascular stiffness and chronic non-infectious inflammation, raising the possibility that CPPs may be an endogenous pro-aging factor. Terrestrial vertebrates with the bone made of calcium- phosphate may be destined to age due to calcium-phosphate in the blood.
Topics: Aging; Animals; Arteriosclerosis; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucuronidase; Humans; Klotho Proteins; Mice; Phosphates
PubMed: 33028781
DOI: 10.5551/jat.RV17045 -
Current Atherosclerosis Reports May 2015AIP1 (ASK1-interacting protein-1; encoded by the DAB2IP gene), a signaling scaffolding protein, is abundantly expressed in vascular endothelial cells (EC). While it was... (Review)
Review
AIP1 (ASK1-interacting protein-1; encoded by the DAB2IP gene), a signaling scaffolding protein, is abundantly expressed in vascular endothelial cells (EC). While it was initially discovered as an apoptosis signal-regulating kinase 1 (ASK1)-interacting protein, AIP1 broadly suppresses inflammatory responses triggered by cytokines and stresses such as TNF, LPS, VEGF, and endoplasmic reticulum (ER) stress in EC (therefore, AIP1 is an anti-inflammatory protein). Human genome-wide association study (GWAS) has identified DAB2IP gene variants conferring susceptibility to cardiovascular diseases. Consistently, a global or vascular EC-specific deletion of DAB2IP in mice strongly enhances inflammatory responses and exacerbates atherosclerosis and graft arteriosclerosis progression in mouse models. Mechanisms for AIP1 function and regulation associated with human cardiovascular diseases need further investigations.
Topics: Adaptor Proteins, Signal Transducing; Animals; Arteriosclerosis; Atherosclerosis; Carrier Proteins; Genome-Wide Association Study; Guanylate Kinases; Humans; Oxidative Stress; Signal Transduction
PubMed: 25732743
DOI: 10.1007/s11883-015-0503-z -
Archives of Pathology & Laboratory... Aug 2009Arteriosclerosis is the vascular disease that is the leading cause of mortality in industrialized countries. Currently, there are 3 lesions within the broader category... (Review)
Review
CONTEXT
Arteriosclerosis is the vascular disease that is the leading cause of mortality in industrialized countries. Currently, there are 3 lesions within the broader category of arteriosclerosis: atherosclerosis, Mönckeberg medial calcific sclerosis, and arteriolosclerosis.
OBJECTIVE
In this review, we discuss the history of the terminology and current classification of arteriosclerosis and problems with the current classification. We also discuss recently described new arterial lesions that are not in the current classification.
DATA SOURCES
In spite of the prevalence and importance of arteriosclerotic vascular disease, and the widespread use of the current terminology, there are major problems with the current classification: (1) the current classification has an inconsistent naming convention, (2) the classification fails to use terms that accurately describe the lesions, and (3) important arterial lesions are absent from the classification. In addition, although the terms arteriosclerosis and atherosclerosis describe different lesions, these terms are often used interchangeably.
CONCLUSION
Consideration should be given for a new more inclusive and accurate classification of "arteriosclerotic" lesions that more accurately reflects the pathology of these important vascular lesions.
Topics: Arteries; Arteriosclerosis; Humans; Terminology as Topic
PubMed: 19653731
DOI: 10.5858/133.8.1309 -
British Journal of Haematology Aug 2004During the past decade, interrelationships between inflammation and thrombosis have been the subject of extensive works, and it is now commonly recognized that... (Review)
Review
During the past decade, interrelationships between inflammation and thrombosis have been the subject of extensive works, and it is now commonly recognized that inflammation (notably leucocyte recruitment) directly affects thrombosis, and that thrombosis also constitutes a pro-inflammatory event. This tight link is partly attributable to P-selectin, which is functional not only when expressed on the surface of activated platelets and endothelial cells, but also when shed, generating its soluble form, termed sP-selectin. In this review, we will provide an overview of the relative roles of the different compartments of P-selectin (platelet, endothelial cell, plasma) in haemostasis and vascular pathologies, and the potential therapeutic benefits achievable in targeting this molecule.
Topics: Arteriosclerosis; Blood Coagulation; Blood Platelets; Endothelial Cells; Endothelium, Vascular; Hemostasis; Humans; Inflammation; P-Selectin; Platelet Activation
PubMed: 15257701
DOI: 10.1111/j.1365-2141.2004.05032.x -
Journal of Medical Genetics Apr 1976There is a growing number of lipoprotein markers recognized by immunological, electrophoretic, and other biochemical methods, and a beginning has been made on studying... (Review)
Review
There is a growing number of lipoprotein markers recognized by immunological, electrophoretic, and other biochemical methods, and a beginning has been made on studying their modes of inheritance and linkage relations. Suggestive but inconclusive evidence of a relation between the cerumen polymorphism and arteriosclerosis has been published. Associations of the ABO blood groups with cardiovascular disease and serum lipid levels have been established, but the exact relation to lipoproteins and atherosclerosis remains to be determined.
Topics: ABO Blood-Group System; Antigens; Arteriosclerosis; Cerumen; Electrophoresis; Genetic Linkage; HLA Antigens; Humans; Infant, Newborn; Lipoproteins; Lipoproteins, LDL; Polymorphism, Genetic
PubMed: 180292
DOI: 10.1136/jmg.13.2.81 -
Circulation Jan 2017
Review
Topics: Arteriosclerosis; Calcinosis; Endothelium, Vascular; Humans; Inflammation Mediators; Osteogenesis
PubMed: 28115412
DOI: 10.1161/CIRCULATIONAHA.116.022562 -
Journal of Atherosclerosis and... 2004It is herein discussed what should be measured as predictors of atherosclerosis, to increase the predictive power of coronary risk evaluation in clinical practice.... (Review)
Review
It is herein discussed what should be measured as predictors of atherosclerosis, to increase the predictive power of coronary risk evaluation in clinical practice. Plasma apolipoprotein (apo)B and apoAI have been reported to be stronger predictors of coronary artery disease (CAD) than plasma low-density lipoprotein (LDL)-cholesterol (C) and high-density lipoprotein (HDL)-C. The estimation of plasma levels of remnants of TG-rich lipoproteins is also important for coronary risk evaluation. An increase in plasma small, dense LDL is a risk factor for CAD. It is not practical to measure plasma small, dense LDL as a routine clinical examination. We should estimate the plasma levels of small, dense LDL by plasma triglyceride (TG), apoB, and HDL-C levels. Oxidized LDL (ox-LDL) plays an important role in atherosclerosis. Further large-scale, prospective studies are necessary to determine whether the measurement of plasma ox-LDL and autoantibodies against ox-LDL is an essential predictor of atherosclerosis. High plasma levels of Lp(a) are a risk factor for atherosclerotic vascular diseases in subjects with high plasma LDL-C levels and multiple coronary risk factors. Metabolic syndrome (MS) has been recognized recently as a predictor of CAD. As a result, it should be elucidated whether MS must be involved in the coronary risk evaluation score because all components of MS are involved in the score. A high plasma level of high-sensitivity C-reactive protein (hs-CRP) is an important predictor of atherosclerotic diseases. Whether it is essential to measure the plasma levels of atherosclerosis surrogate markers in clinical practice remains to be elucidated. It is concluded that plasma levels of apoB, apoAI, remnant-like particle (RLP)-C, lipoprotein (a) [Lp(a)], and hs-CRP in addition to those of lipids should be measured as predictors of atherosclerosis in clinical practice. We need to establish a new atherosclerosis risk evaluation scoring system involving the above factors, based on large-scale, prospective studies, to prevent atherosclerotic vascular diseases. In Japan, plasma levels of Lp(a), RLP-C, and hs-CRP are routinely measured in clinical practice. As a result, it would be rather easy to establish a new atherosclerosis risk evaluation scoring system in Japan.
Topics: Arteriosclerosis; Humans; Lipids; Predictive Value of Tests; Risk Factors
PubMed: 15557708
DOI: 10.5551/jat.11.265