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)

Isotretinoin treatment alters the plasma lipid levels but the mechanisms and the effects on the metabolism of triglyceride-rich lipoproteins such as chylomicrons and very-low-density lipoproteins remain unclear. We investigated the effect of isotretinoin on the plasma kinetics of emulsion models of triglyceride-rich lipoproteins and the lipid profile. Ten patients with acne were treated with 0.8 mg/kg of isotretinoin over 4 weeks for comparison with non-treated acne patients. In both groups the plasma kinetic study of a triglyceride-rich emulsion double-labeled with 14C-cholesterol oleate and 3H-triolein was performed after intravenous injection of the emulsion and radioactive counting in plasma samples collected over 60 min. Patients using isotretinoin showed decreased removal from the plasma of the 3H-triglyceride (median 0.019 min-1 TG) compared with controls (median 0.044 min-1, P=0.007), and the removal of the emulsion 14C-cholesterol oleate also tended to be decreased (treatment: 0.011 min-1; controls: 0.024 min-1, P=0.06). The values of total and LDL cholesterol and triglycerides were increased post-treatment (P<0.03). In conclusion, while increasing the fasting plasma concentration of VLDL and LDL, which are traditional risk factors for atherosclerosis, isotretinoin treatment also slows down the metabolism of triglyceride-rich lipoproteins such as chylomicrons, as tested by the emulsion model, an effect that is also increasingly recognized as atherogenic.
Arch Dermatol Res 2006 Mar
PMID:Effects of isotretinoin on the metabolism of triglyceride-rich lipoproteins and on the lipid profile in patients with acne. 1642 99

Nicotinic acid, used for atherosclerosis treatment, has an adverse effect of skin flushing. The flushing mechanism, thought to be caused by the release of prostaglandin D(2) (PGD(2)), is not well understood. We aimed to identify which cells mediate the flushing effect. Nicotinic acid receptor (GPR109A) gene expression was assessed in various tissues and cell lines. Cells expressing GPR109A mRNA were further assayed for PGD(2) release in response to nicotinic acid. Of all samples, only skin was able to release PGD(2) upon stimulation with nicotinic acid. The responsive cells were localized to the epidermis, and immunocytochemical studies revealed the presence of GPR109A on epidermal Langerhans cells. CD34+ cells isolated from human blood and differentiated into Langerhans cells (hLC-L) also showed GPR109A expression. IFNgamma treatment increased both mRNA and plasma membrane expression of GPR109A. IFNgamma-stimulated hLC-Ls released PGD(2) in response to nicotinic acid in a dose-dependant manner (effector concentration for half-maximum response=1.2 mM+/-0.7). Acifran, a structurally distinct GPR109A ligand, also increased PGD(2) release, whereas isonicotinic acid, a nicotinic acid analog with low affinity for GPR109A, had no effect. These results suggest that nicotinic acid mediates its flushing side effect by interacting with GPR109A on skin Langerhans cells, resulting in release of PGD(2).
J Invest Dermatol 2006 Dec
PMID:Langerhans cells release prostaglandin D2 in response to nicotinic acid. 1700 71

Skin is the largest body organ that serves as an important environmental interface providing a protective envelope that is crucial for homeostasis. On the other hand, the skin is a major target for toxic insult by a broad spectrum of physical (i.e. UV radiation) and chemical (xenobiotic) agents that are capable of altering its structure and function. Many environmental pollutants are either themselves oxidants or catalyze the production of reactive oxygen species (ROS) directly or indirectly. ROS are believed to activate proliferative and cell survival signaling that can alter apoptotic pathways that may be involved in the pathogenesis of a number of skin disorders including photosensitivity diseases and some types of cutaneous malignancy. ROS act largely by driving several important molecular pathways that play important roles in diverse pathologic processes including ischemia-reperfusion injury, atherosclerosis, and inflammatory responses. The skin possesses an array of defense mechanisms that interact with toxicants to obviate their deleterious effect. These include non-enzymatic and enzymatic molecules that function as potent antioxidants or oxidant-degrading systems. Unfortunately, these homeostatic defenses, although highly effective, have limited capacity and can be overwhelmed thereby leading to increased ROS in the skin that can foster the development of dermatological diseases. One approach to preventing or treating these ROS-mediated disorders is based on the administration of various antioxidants in an effort to restore homeostasis. Although many antioxidants have shown substantive efficacy in cell culture systems and in animal models of oxidant injury, unequivocal confirmation of their beneficial effects in human populations has proven elusive.
J Invest Dermatol 2006 Dec
PMID:Oxidative stress in the pathogenesis of skin disease. 1710 3

Werner's syndrome (adult onset progeria) is a rare form of autosomal recessive genodermatosis associated in almost 80% of cases with mutation of the WRN gene. This prototype of rapid ageing syndromes is characterized by short stature with skin and hair anomalies (early graying of the hair, alopecia, depilation, sclerosed skin), orthopedic complications (flat foot, hallux valgus and other joint deformations) as well as systemic signs (early cataract, premature and diffuse atherosclerosis, endocrinopathies) and high risk of certain types of cancer (sarcomas, myeloid blood dyscrasias). Death occurs around the age of 40 - 50 years mainly as a result of cardiovascular accident or development of a malignant tumour. Signs of early aging should evoke this basic diagnosis and arrangements should be made for appropriate follow-up with screening for and treatment of systemic complications.
Ann Dermatol Venereol 2007 Feb
PMID:[Werner's syndrome (adult onset progeria)]. 1737 9

Werner syndrome (WS, MIM#277700) is a very rare autosomal recessive disorder. WS clinical signs include altered distribution of subcutaneous fat, juvenile bilateral cataracts, a mask-like face and bird-like nose, trophic ulcers of the feet, diabetes mellitus, and premature atherosclerosis. The habitus is characteristic, with short stature, stocky trunk and slender extremities. WS frequency has been roughly estimated to be 1: 100,000 in Japan and 1: 1,000,000-1: 10,000,000 outside of Japan. The only exception to the latter data can be seen in the clustering of WS in Sardinia. Since 2001, 5 new cases have been observed: 4 members of the same family and 1 sporadic case. Therefore, since 1982 the total number of cases described in North Sardinia amounts to 18: 15 are familial (11 members of the same family group) and 3 sporadic. A short clinical description of the 5 new cases is reported.
Eur J Dermatol
PMID:Epidemiology and clinical aspects of Werner's syndrome in North Sardinia: description of a cluster. 1747 82

Epidemiological studies have shown that, in psoriasis patients, associated disorders may occur more frequently than expected. Such comorbidities include psoriatic arthritis, psoriatic pustular diseases, Crohn disease, and signs of metabolic syndrome, which leads to atherosclerosis with coronary heart disease. Although the disorders represent separate entities, they appear to follow overlapping pathogenic pathways. Comorbidities often become clinically manifest years after onset of psoriasis and are frequently seen in severe disease. Persistent low-grade inflammation with secretion of proinflammatory cytokines (eg, tumor necrosis factor alpha) favors the development of insulin resistance and metabolic syndrome. In addition, biochemical and immunologic observations point toward an inflammatory immune mechanism that uses tools of the innate defense armamentarium.
Clin Dermatol
PMID:Comorbidities in psoriasis. 1802 89

The prevalence of the metabolic syndrome is rising, particularly in developed countries, and this is largely driven by increasing obesity and sedentarity rates. Regardless of the definition, the prevalence found in France was lower than in North America and in other European countries; it varied from 11.7 p. cent in men and 7.5 p. cent in women according to the National Cholesterol Education Program (NCEP) definition to 26 p. cent in men and 18.4 p. cent in women according to the International Diabetes Federation (IDF) definition. The presence of the metabolic syndrome promotes the occurrence of type 2 diabetes and clinical atherosclerosis. Relative risk of cardiovascular morbidity and mortality is close to 2 in subjects with metabolic syndrome. The informative value of identifying metabolic syndrome has been demonstrated in the general population as well as in hypertensive subjects. However, it could provide only limited clinical value for cardiovascular disease risk stratification in type 2 diabetes mellitus.
Ann Dermatol Venereol 2008 Feb
PMID:[Metabolic syndrome: epidemiology and its risks]. 1846 92

Cannabis arteritis is a serious peripheral vascular disease affecting young adults consuming cannabis. An increasing number of cases have been recently reported in Europe. The risk of amputation is high. Cannabis arteritis is often confused with atherosclerosis. We present a new case in which complete arterial revascularization was obtained with early aspirin treatment. Cannabis arteritis should be therefore distinguished from peripheral arterial disease caused by atherosclerosis, which is typically not reversible. Early diagnosis and treatment are essential to avoid an irreversible vascular occlusion and amputation.
J Am Acad Dermatol 2008 May
PMID:Cannabis arteritis. 1848 50

Inflammation plays a key role in the pathogenesis of a number of chronic inflammatory systemic diseases (CISDs), including psoriasis, rheumatoid arthritis, systemic lupus erythematosus and Crohn's disease, and also in the pathogenesis of atherosclerosis. CISDs and cardiovascular diseases, such as atherosclerosis, share common pathogenic features, and cardiovascular disease is an important cause of morbidity and mortality in patients with CISDs. Activated inflammatory cells and pro-inflammatory cytokines contribute to the development of psoriatic lesions and play an important role in the breakdown of atherosclerotic plaques. Psoriasis and atherosclerosis also have similar histological characteristics involving T cells, macrophages and monocytes. In particular, the extravasation of T cells through the epithelium is characteristic of both psoriatic and atherosclerotic plaques. Cardiovascular disease is an important cause of morbidity and mortality in patients with psoriasis, which is associated with an increased cardiovascular risk profile compared with the general population. Patients with psoriasis are at increased risk of arterial hypertension, coronary heart disease, hyperlipidaemia, obesity and type II diabetes, which are more prevalent than in control patients. This increased risk could be due to the effects of chronic inflammatory changes, particularly the infiltration of T cells and subsequent secretion of pro-inflammatory cytokines. Some drugs used in the treatment of cardiovascular disease, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors have anti-inflammatory activity. In addition, systemic treatments for psoriasis may, by decreasing inflammation, reduce the risk of cardiovascular disease. It is suggested, therefore, that an integrated approach to the treatment of the inflammatory processes underlying both psoriasis and atherosclerosis may be beneficial in reducing cardiovascular risk in patients with psoriasis. The newer targeted biological therapies, such as efalizumab and infliximab, which offer the potential for long-term disease control in psoriasis, may be of particular use in this setting.
Br J Dermatol 2008 Aug
PMID:Inflammation in atherosclerosis and psoriasis: common pathogenic mechanisms and the potential for an integrated treatment approach. 1870 Sep 10

Psoriasis is highly prevalent and is associated with skin-associated complaints as well as arthritis, depression and a lower quality of life. Recently, it has been demonstrated that not only do patients with psoriasis have an increased prevalence of cardiovascular risk factors, but an increased risk of myocardial infarction, and for those with severe disease, increased mortality. Dermatologists and other health professionals need to be cognizant of this association and ensure that cardiovascular risk factors are evaluated and treated appropriately in those patients with psoriasis. We review the association between psoriasis, atherosclerosis and inflammation, as well as some treatable cardiovascular risk factors that may prove beneficial in reducing a patient's cardiovascular risk.
Br J Dermatol 2009 Jan
PMID:Psoriasis: an opportunity to identify cardiovascular risk. 1961 48


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