Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polyvascular disease is the disease that includes the simultaneous existence of atherosclerotic process on coronary, carotid and lower extremities peripheral arteries. It is very difficult, if not impossible to determine the prevalence of atherosclerosis, because it is one predominant asymptomatic illness. There is no correct information related to atherosclerosis clinical readings, that is to it's most important consequences: coronary heart disease, cerebrovascular disease and peripheral blood vessels obstruction. Atherosclerosis is a complex disease with numerous predisposing factors that we call the risk factors. We divide all atherosclerotic risk factors on changeable and unchangeable (age, sex and heredity). The risk factors can further be divided on classical (conventional) and non-traditional (raised oxidative stress, endothelium disfunction and inflammation). Tobacco smoking can result by the sevenfold risk increase of peripheral arteries disease and at least the double risk increase of coronary arteries disease beginning. These two main forms of cardiovascular diseases, related with tobacco smoking, are the main atherothrombosis consequences. Obesity has overcome the global epidemical proportions with more than one million people with excessively body mass and, at least, 300 millions of clinical obese people. Obesity is considered as chronic inflammation disease that leads towards the chronic mass non-inflammation diseases as atherosclerosis, Diabetes type 2, non-alcohol stetosis of liver, cancer (of prostate, of breast) and osteoarthrosis.
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PMID:[Tobacco smoking and obesity as risk factors of polyvascular atherosclerosis]. 1953 64

YKL-39 is a Glyco_18 domain containing chitinase-like protein which is currently recognized as a biomarker for the activation of chondrocytes and the progress of the osteoarthritis in human. YKL-39 was identified as an abundantly secreted protein in primary culture of human articular chondrocytes. Two biological activities of YKL-39 might contribute to the disease progression. One is the induction of autoimmune response and second is the participation in tissue remodeling. Other mammalian chitinase-like proteins including chitotriosidase, SI-CLP, YKL-40 and YM1 are expressed by macrophages in various pathological conditions. In contrast, YKL-39 was never reported to be produced by macrophages. We used in vitro model of human monocyte-derived macrophage differentiation to analyse regulation of YKL-39 expression. Expression of YKL-39 was examined by real-time RT-PCR. CD14+ MACS sorted human monocytes differentiated for 6 days under different stimulations including IFNgamma, IL-4, dexamethasone and TGF-beta. We found that both IL-4 and TGF-beta have weak stimulatory effect on YKL-39 expression in all donors tested (3.2 +/- 1.7 fold, p = 0.006 and 6.3 +/- 3.1 fold, p = 0.014 respectively). However the combination of IL-4 and TGF-beta had strong stimulatory effect on the expression of YKL-39 in all analysed individual macrophage cultures (34 +/- 36 fold, p = 0.05). IFN-gamma did not show statistically significant effect of YKL-39 mRNA expression. Presence of dexamethasone almost completely abolished the stimulatory effects of IL-4 and TGF-beta. In summary, we show here for the first time, that human cells of monocyte origin are able to produce YKL-39. Maturation of monocyte derived macrophages in the presence of Th2 cytokine IL-4 and TGF-beta leads to the strong activation of YKL-39 expression. Thus elevated levels of YKL-39 observed during chronic inflammations can not be attributed solely to the activity of chondrocytes. In perspective, YKL-39 might serve as a useful biomarker to detect macrophage-specific response in pathologies like tumour, atherosclerosis and Alzheimer disease.
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PMID:Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages. 1957 92

The endocannabinoid system is an ancient lipid signaling network which in mammals modulates neuronal functions, inflammatory processes, and is involved in the aetiology of certain human lifestyle diseases, such as Crohn's disease, atherosclerosis and osteoarthritis. The system is able to downregulate stress-related signals that lead to chronic inflammation and certain types of pain, but it is also involved in causing inflammation-associated symptoms, depending on the physiological context. The cannabinoid type-2 (CB(2)) receptor, which unlike the CB(1) receptor does not induce central side effects, has been shown to be a promising therapeutic target. While CB(1) receptor antagonists/inverse agonists are of therapeutic value, also CB(2) receptor ligands including agonists are of pharmacological interest. Although the endocannabinoid system is known to be involved in the regulation of energy homoeostasis and metabolism (mainly via CB(1) receptors) there was hitherto no direct link between food intake and cannabinoid receptor activation. Our recent finding that beta-caryophyllene, a ubiquitous lipohilic plant natural product, selectively binds to the CB(2) receptor and acts as a full agonist is unexpected. Maybe even more unexpected is that oral administration of this dietary compound exerts potent anti-inflammatory effects in wild type mice but not in CB(2) receptor (Cnr2(-/-)) knockout mice. Like other CB(2) ligands also beta-caryophyllene inhibits the pathways triggered by activation of the toll-like receptor complex CD14/TLR4/MD2, which typically lead to the expression of proinflammatory cytokines (IL-1beta, IL-6; IL-8 and TNFalpha) and promotes a TH(1) immune response. In this addendum, the CB(2) receptor-dependent effect of beta-caryophyllene on LPS-triggered activation of the kinases Erk1/2 and JNK1/2 are further discussed with respect to the possibility that both CB(2) inverse agonists and agonists, independent of their G-protein signaling, may block LPS-triggered activation of MAPKs, leading to inhibition of proinflammatory cytokine expression and attenuation of inflammation.
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PMID:Anti-inflammatory cannabinoids in diet: Towards a better understanding of CB(2) receptor action? 1970 83

The rheumatic diseases have been associated with accelerated atherosclerosis. Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by persistent synovial inflammation which leads to disability and structural changes in joints. Epidemiological studies have demonstrated an increased cardiovascular mortality in patients with RA. In these patients, atherosclerotic plaque occurs earlier, and it has a faster evolution than in general population. Atherosclerosis (AT) is also an inflammatory disease partly mediated by cytokines, many of them involved on chronic synovitis. Our group has developed a rabbit experimental model of AT aggravated by chronic arthritis to study inflammatory mechanisms involved on the progression of vascular lesions and their response to drugs. A preliminary study using this model suggests a beneficial effect of chondroitin sulphate (CS), a drug recommended for the treatment of osteoarthritis, in controlling AT lesions. Yet clinical trials should be conducted with this compound to address the same hypothesis in human studies.
Osteoarthritis Cartilage 2010 Jun
PMID:Improvement of experimental accelerated atherosclerosis by chondroitin sulphate. 2039 96

Chronic inflammation is associated with aging and plays a causative role in several age-related diseases such as cancer, atherosclerosis and osteoarthritis. The source of this chronic inflammation is often attributed to the progressive activation of immune cells over time. However, recent studies have shown that the process of cellular senescence, a tumor suppressive stress response that is also associated with aging, entails a striking increase in the secretion of proinflammatory proteins and might be an important additional contributor to chronic inflammation. Here, we list the secreted factors that make up the proinflammatory phenotype of senescent cells and describe the impact of these factors on tissue homeostasis. We also summarize the cellular pathways/processes that are known to regulate this phenotype--namely, the DNA damage response, microRNAs, key transcription factors and kinases and chromatin remodeling.
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PMID:Inflammatory networks during cellular senescence: causes and consequences. 2044 48

Matrix metalloproteinases (MMPs) have a great variability that provides a complex intervention in pathophysiological conditions. MMPs roles in pathology may be grouped into the following main types: (1) tissue destruction, as in cancer invasion and metastasis, rheumatoid arthritis, osteoarthritis, different types of ulcers, periodontal disease, brain injury and neuroinflammatory diseases; (2) fibrosis, as in liver cirrhosis, fibrotic lung disease, otosclerosis, atherosclerosis, and multiple sclerosis; (3) weakening of matrix, as in dilated cardiomyopathy, epidermolysis bullosa, aortic aneurysm and restenotic lesions. Recent data also adds new MMPs functions in angiogenesis and apoptosis. Interesting opposite intervention in escaping mechanisms vs. antitumor defensive mechanisms had been also reported. As MMP-7 is expressed by tumor cells of epithelial and mesenchymal origin, it may be used as a biological marker of an aggressive phenotype and as a target of therapeutic intervention. MMPs play a pivotal role in the pathogenesis of arthritis, atherosclerosis, pulmonary emphysema, and endometriosis. Although MMP involvement in pathology is more than simple excessive matrix degradation, or an imbalance between them and their specific tissular inhibitors (TIMPs), MMP inhibition may be of therapeutic benefit, so synthetic MMPs inhibitors had been developed and are currently under clinical testing.
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PMID:Matrix metalloproteinases involvement in pathologic conditions. 2049 35

An impressive range of tissues and cells are regulated by mechanical loading, and this regulation is central to disease processes such as osteoporosis, atherosclerosis, and osteoarthritis. However, other than a small number of specialized excitable cells involved in hearing and touch, cellular mechanosensing mechanisms are generally quite poorly understood. A lack of mechanistic understanding of these processes is one of the primary foci of the nascent field of mechanobiology, which, as a consequence, enjoys enormous potential to make critical new insights into both physiological function and etiology of disease. In this review we outline the process in bone by tracing mechanical effects from the organ level to the cellular and molecular levels and by integrating the biological response from molecule to organ. A case is made that a fundamental roadblock to advances in mechanobiology is the dearth of information in the area of pericellular mechanics.
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PMID:Osteocyte mechanobiology and pericellular mechanics. 2061 41

The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteases are secreted enzymes that regulate extracellular matrix turnover by degrading specific matrix components. Roles for the proteases in inflammation and atherosclerosis have been suggested by a number of recent studies, and the role of ADAMTS-4 and -5 in the breakdown of aggrecan and subsequent degradation of cartilage during osteoarthritis has also been established. The ability of the ADAMTS proteases to degrade versican, the primary proteoglycan in the vasculature, is thought to be central to any hypothesized role for the proteases in atherosclerosis. In this review, we introduce the structure and function of the ADAMTS family of proteases and review the literature that links them with inflammation and atherosclerosis.
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PMID:ADAMTS proteases: key roles in atherosclerosis? 2065 28

Extracellular membrane vesicles (MVs) 30-1000 nm in diameter and of varying cellular origins are increasingly recognized for their participation in a range of processes, including the pathogenesis of various diseases, such as: (1) atherosclerosis, (2) thromboembolism, (3) osteoarthritis (OA), (4) chronic renal disease and pulmonary hypertension, (5) tissue invasion and metastasis by cancer cells, (6) gastric ulcers and bacterial infections, and (7) periodontitis. MVs are derived from many different cell types and intracellular mechanisms, and perform different metabolic functions or roles, depending on the cell of origin.The presence of a metabolically active, outer membrane is a distinguishing feature of all MVs, regardless of their cell type of origin and irrespective of terminologies applied to them such as exosomes, microparticles, or matrix vesicles. The MV membrane provides one of the few protected and controlled internal microenvironments outside cells in which specific metabolic objectives of the host cell may be pursued vigorously at a distance from the host cell. MVs are also involved in various forms of normal and abnormal intercellular communication. Evidence is emerging that circulating MVs are good predictors of the severity of several diseases. In addition, recently, the role of MVs in inducing immunity against cancer cells and bacterial infections has become a topic of interest to researchers in the area of therapeutics. The main objective of this review is to list and briefly describe the increasingly well-defined roles of MVs in selected diseases in which they seem to have a significant role in pathogenesis.
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PMID:Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis. 2080 91

Osteoarthritis (OA) is an age-related degenerative disease comprising the main reason of handicap in the Western world. Interestingly, to date, there are neither available biomarkers for early diagnosis of the disease nor any effective therapy other than symptomatic treatment and joint replacement surgery. OA has long been associated with obesity, mainly due to mechanical overload exerted on the joints. Recent studies however, point to the direction that OA is a metabolic disease, as it also involves non-weight bearing joints. In fact, altered lipid metabolism may be the underlying cause. First, adipokines have been shown to be key regulators of OA pathogenesis. Second, epidemiological studies have shown serum cholesterol to be a risk factor for OA development. Third, lipid deposition in the joint is observed at the early stages of OA before the occurrence of histological changes. Fourth, proteomic analyses have shown an important connection between OA and lipid metabolism. Finally, recent gene expression studies reveal a deregulation of cholesterol influx and efflux and in the expression of lipid metabolism-related genes. Interestingly, lipids and lipid metabolism are known to be implicated in the development and progression of another age-related degenerative disease, atherosclerosis (ATH). Thus, although it is tempting to speculate that the osteoarthritic chondrocyte has been transformed to foam cell, it has not been proven yet. However, this may be an intriguing theory linking ATH and OA, which may open new avenues to novel therapeutic interventions for OA taking advantage of previous knowledge from ATH.
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PMID:Lipid metabolism and osteoarthritis: lessons from atherosclerosis. 2111 41


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