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)

Platelet 12-lipoxygenase is believed to play a role in cancer and other pathological conditions, such as psoriasis, atherosclerosis and arthritis. The inhibition of 12-LOX is a potential therapeutic approach in the treatment of tumor metastasis. The extracts of Euclea racemosa Murr. ssp. schimperi (A. DC.) F. White (Ebenaceae) obtained by maceration and naphthoquinones isolated from the dichloromethane extract have been investigated for their 12(S)-HETE inhibitory activity using human platelets. At 100 microg/ml, the dichloromethane extract inhibited the formation of 12(S)-HETE by 88.7% and compounds 7-methyljuglone (2), isodiospyrin (3), neodiospyrin (4) and mamegakinone (5), isolated from this extract, exhibited significant activities with IC(50) values ranging from 4 to 58 microg/ml (22.2-155.7 microM). Of these the most abundant compound, 7-methyljuglone displayed a potent inhibitory activity with an IC(50) value of 4.18 microg/ml (22.2 microM), which was comparable to the positive control baicalein with an IC(50) value of 5 microg/ml (18.5 microM). In contrast, 4(S)-shinanolone (1), the reduced form of compound 2, did not show any significant inhibitory activity even at a concentration of 60 microg/ml.
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PMID:In vitro 12(S)-HETE inhibitory activities of naphthoquinones isolated from the root bark of Euclea racemosa ssp. schimperi. 1601 77

The metabolism of arachidonic acid can be catalysed by either one of two enzyme families: the cyclooxygenases or the lipoxygenases. The lipoxygenase enzymes are classed into several subcategories including 5-, 12- and 15-lipoxygenases. The 5-lipoxygenase pathway has been the major focus of study due to the pronounced pro-inflammatory role of leukotrienes and the approval of 5-lipoxygenase inhibitors and leukotriene receptor antagonists for the clinical treatment of asthma. Although less well characterized, the 12-lipoxygenase as well as the 15-lipoxygenase pathway may also play an important role in the progression of human diseases such as cancer, psoriasis and atherosclerosis. The present review article summarizes the findings from an extensive literature search on plants that have been assessed for 12- and 15-lipoxygenase inhibitory activity as well as for leukotriene receptor antagonistic properties. The results are presented in a tabular format, and a discussion about promising plant species and natural compounds as well as relevant in vitro assays are included in this article.
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PMID:Lipoxygenase inhibitors from natural plant sources. Part 2: medicinal plants with inhibitory activity on arachidonate 12-lipoxygenase, 15-lipoxygenase and leukotriene receptor antagonists. 1604 64

Angiotensin-II regulates vascular tone, stimulates the release of pro-inflammatory cytokines, activates NF-kappaB, increases oxidant stress, and suppresses nitric oxide synthesis, and thus, it functions as an inflammatory molecule. Since ACE is present in many tissues, this suggests that angiotensin-II may play a significant role in atherosclerosis, congestive cardiac failure, stroke, bipolar disorder, schizophrenia, dementia, Alzheimer's disease, psoriasis, atopic and non-atopic dermatitis, eczema, several acute and chronic inflammatory diseases, and cancer, conditions in which inflammation is an aetiopathogenic factor. Thus, ACE inhibitors and/or angiotensin-II receptor blockers could be of benefit in these conditions. Furthermore, structural analogues of ACE inhibitors and angiotensin-II receptor blockers could be developed that possess anti-inflammatory actions without significant action on the cardiovascular system.
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PMID:Angiotensin-II behaves as an endogenous pro-inflammatory molecule. 1612 58

Angiogenesis is the process by which new blood vessels are formed from existing vessels. Mammalian populations harbor genetic variations that alter angiogenesis. Some of these changes result in Mendelian traits of variable penetrance, with telangiectasia being a common symptom. Other more subtle variations exist, with promoter variations in the VEGF gene being of particular interest. Genetic diversity in angiogenesis-regulating genes has been linked to increased susceptibility to multiple angiogenesis-dependent diseases in humans. These diseases include cancer, arthritis, atherosclerosis, and cardiovascular disease, endometriosis, diabetic retinopathy, retinopathy of prematurity, psoriasis, and sarcoidosis. Also, multiple disturbances in pregnancy including miscarriage, spontaneous preterm delivery, and severe pre-eclampsia have been linked to alterations in angiogenesis-regulating genes. Present efforts to dissect the complexity of the genetic diversity that regulates angiogenesis have used laboratory animals due to the availability of genome sequence for many species and the ability to perform high volume controlled breeding. Ongoing mapping studies have identified multiple loci that control angiogenic responsiveness in several mouse models. Genetic alterations responsible for discrete angiogenic alterations will then be studied in appropriate mouse disease models.
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PMID:The effect of genetic diversity on angiogenesis. 1632 83

Tumor necrosis factor (TNF), initially discovered as a result of its antitumor activity, has now been shown to mediate tumor initiation, promotion, and metastasis. In addition, dysregulation of TNF has been implicated in a wide variety of inflammatory diseases including rheumatoid arthritis, Crohn's disease, multiple sclerosis, psoriasis, scleroderma, atopic dermatitis, systemic lupus erythematosus, type II diabetes, atherosclerosis, myocardial infarction, osteoporosis, and autoimmune deficiency disease. TNF, however, is a critical component of effective immune surveillance and is required for proper proliferation and function of NK cells, T cells, B cells, macrophages, and dendritic cells. TNF activity can be blocked, either by using antibodies (Remicade and Humira) or soluble TNF receptor (Enbrel), for the symptoms of arthritis and Crohn's disease to be alleviated, but at the same time, such treatment increases the risk of infections, certain type of cancers, and cardiotoxicity. Thus blockers of TNF that are safe and yet efficacious are urgently needed. Some evidence suggests that while the transmembrane form of TNF has beneficial effects, soluble TNF mediates toxicity. In most cells, TNF mediates its effects through activation of caspases, NF-kappaB, AP-1, c-jun N-terminal kinase, p38 MAPK, and p44/p42 MAPK. Agents that can differentially regulate TNF expression or TNF signaling can be pharmacologically safe and effective therapeutics. Our laboratory has identified numerous such agents from natural sources. These are discussed further in detail.
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PMID:TNF blockade: an inflammatory issue. 1633 57

Clinical and epidemiologic studies have suggested an association between infectious agents and chronic inflammatory disorders and cancer. Better understanding of microbial pattern-recognition receptors and innate immune signaling pathways of the host is helping to elucidate the connection between microbial infection and chronic disease. We propose that a key aspect of pathogenesis is an aberrant epithelial barrier that can be instigated by microbial toxins, environmental insults, or the genetic predisposition of the host. Loss of epithelial integrity results in activation of resident inflammatory cells by microbial invaders or endogenous ligands. When coupled with a failure of normal control mechanisms that limit leukocyte activation, a cascade is established that induces chronic inflammation and its consequences. Here, we outline this mechanistic framework and briefly review how alteration of innate immune response genes in murine models can provide insights into the potential microbial origins of diverse conditions including Crohn's disease, psoriasis, atherosclerosis, diabetes, and liver cancer.
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PMID:Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. 1649 91

Angiogenesis, the generation of new capillaries through a process of pre-existing microvessel sprouting, is under stringent control and normally occurs only during embryonic and post-embryonic development, reproductive cycle, and wound repair. However, in many pathological conditions (solid tumor progression, metastasis, diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among others), the disease appears to be associated with persistent upregulated angiogenesis. The development of specific anti-angiogenic agents arises as an attractive therapeutic approach for the treatment of cancer and other angiogenesis-dependent diseases. The formation of new blood vessels is a complex multi-step process. Endothelial cells resting in the parent vessels are activated by an angiogenic signal and stimulated to synthesize and release degradative enzymes allowing endothelial cells to migrate, proliferate and finally differentiate to give rise to capillary tubules. Any of these steps may be a potential target for pharmacological intervention. In spite of the disappointing results obtained initially in clinical trials with anti-angiogenic drugs, recent reports with positive results in phases II and III trials encourage expectations in their therapeutic potential. This review discusses the current approaches for the discovery of new compounds that inhibit angiogenesis, with emphasis on the clinical developmental status of anti-angiogenic drugs.
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PMID:Anti-angiogenic drugs: from bench to clinical trials. 1665 70

Psoriasis is a chronic inflammatory skin disease that is associated with an increased cardiovascular risk profile. The systemic inflammation present in psoriasis, various systemic treatments for psoriasis and an increased prevalence of unhealthy life style factors may all contribute to this unfavorable risk profile. The purpose of this article is to provide an overview of what is known about these risk factors in psoriasis, the way they influence the cardiovascular risk of psoriasis patients, and what can be done to reduce this risk. Genetic studies demonstrate that psoriasis and cardiovascular disease share common pathogenic features in which, for example inflammatory cytokines like TNF-alpha and IL-1 play an important role. The chronic inflammation in psoriasis has an unfavorable effect on the cardiovascular risk profile. Multiple cardiovascular risk factors seem to be influenced; the blood pressure, oxidative stress, dyslipidemia, endothelial cell dysfunction, homocysteine levels and blood platelet adhesion. Moreover, classic cardiovascular risk factors like smoking and obesity that have an increased prevalence among patients with psoriasis, indirectly also worsen the cardiovascular risk profile by stimulating the psoriasis activity. Systemic treatments in psoriasis reduce the cardiovascular risk by diminishing the inflammation, but it should be taken into account that most therapies also have adverse cardiovascular effects like dyslipidemia, hyperhomocysteinemia and hypertension. As a consequence preventive measures may be indicated at least during long-term treatments. Prospective research is warranted to accurately estimate the increased cardiovascular risk in psoriasis, to determine the underlying processes and to consider preventive measures according to the absolute risk of cardiovascular disease. The present overview provides data to advice health care providers to pay more attention to the cardiovascular risk profile in psoriasis patients.
Atherosclerosis 2007 Jan
PMID:Unfavorable cardiovascular risk profiles in untreated and treated psoriasis patients. 1694 72

Inflammation is traditionally viewed as a physiological reaction to tissue injury. Leukocytes contribute to the inflammatory response by the secretion of cytotoxic and pro-inflammatory compounds, by phagocytotic activity and by targeted attack of foreign antigens. Leukocyte accumulation in tissues is important for the initial response to injury. However, the overzealous accumulation of leukocytes in tissues also contributes to a wide variety of diseases, such as atherosclerosis, chronic inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, vasculitis, systemic inflammatory response syndrome, juvenile diabetes and psoriasis. Many therapeutic interventions target immune cells after they have already migrated to the site of inflammation. This review addresses different therapeutic strategies, used to reduce or prevent leukocyte-endothelial cell interactions and communication, in order to limit the progression of inflammatory diseases.
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PMID:Therapeutic targeting of molecules involved in leukocyte-endothelial cell interactions. 1695 69

Inflammation is a physiological response to a foreign organism such as bacteria, dust particles, and viruses. Recent studies have enlightened the role of inflammation in the progression of a variety of diseases such as cancer, atherosclerosis, asthma, and psoriasis. This article is a brief overview of the inflammatory processes involved in the progression of these common diseases. Knowledge about these mechanisms can shed light into development of newer therapeutic agents that are aimed at the eradication of these diseases.
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PMID:Inflammation and disease progression. 1710 50


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