Increased leukotriene concentrations in gingival crevicular fluid from subjects with periodontal disease and atherosclerosis

Bäck, Magnus; Airila‐Månsson, Stella; Jogestrand, Tomas; Söder, Birgitta; Söder, Per‐Östen

doi:10.1016/j.atherosclerosis.2006.07.003

Cited by 36 publications

(41 citation statements)

References 30 publications

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“…Based on findings in different animal models of atherosclerosis [29], beneficial effects could be anticipated by anti-LT treatments. Although some findings in humans based on either genetic associations [25][26][27][28] or LT measurements in different patient populations [20,21,24,58], support this notion, it may currently be premature to conclude on what exact mechanisms to target in human disease. Some interesting information can however be obtained through studies of other pathologies in which anti-LT treatments already have been evaluated [12,14].…”

Section: Resultsmentioning

confidence: 99%

“…Some interesting information can however be obtained through studies of other pathologies in which anti-LT treatments already have been evaluated [12,14]. In the latter context, the effects of LT inhibition is of particular interest in the context of diseases associated with an increased cardiovascular risk, such as COPD and periodontitis [14,20]. The challenge is now to extrapolate experimental findings to a clinical setting in order to identify patients groups that would benefit from an inhibited LT signaling.…”

Section: Resultsmentioning

confidence: 99%

“…Periodontal disease is for example associated with the development of early atherosclerotic lesions in the carotid artery [17], and an increased risk of stroke [18] and myocardial infarction [19]. The notion of LTs as common mediators of atherosclerosis and periodontal disease was recently suggested in a study associating high levels of cysteinyl-LTs in gingival crevicular fluid with an increased carotid artery wall thickness [20]. Chronic inflammation in the oral cavity can also be measured in the saliva, in which high LT concentrations have been demonstrated [21,22], and reported to be inhibited by zileuton [23], an anti-asthmatic LT synthesis inhibitor (Fig.…”

Section: Proinflammatory Leukotriene Signaling In Atherosclerosismentioning

confidence: 99%

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Leukotriene Signaling in Atherosclerosis and Ischemia

Bäck

2008

Cardiovasc Drugs Ther

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121

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Proinflammatory Leukotriene Signaling In Atherosclerosismentioning

confidence: 99%

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Leukotriene Signaling in Atherosclerosis and Ischemia

Bäck

2008

Cardiovasc Drugs Ther

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121

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“…Concentrations of CysLTs were measured using an enzyme immunoassay kit from Cayman Chemicals with a monoclonal antibody recognizing the total of all 3 CysLTs (LTC 4 , LTD 4 , and LTE 4 ), as previously described. 29 …”

Section: Valve Conditioned Mediamentioning

confidence: 99%

Upregulation of the 5-Lipoxygenase Pathway in Human Aortic Valves Correlates With Severity of Stenosis and Leads to Leukotriene-Induced Effects on Valvular Myofibroblasts

et al. 2011

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Background-The development of aortic valve stenosis is not only associated with calcification and extracellular matrix remodeling, but also with inflammation. The aim of this study was to determine the role of proinflammatory signaling through the leukotriene (LT) pathway in aortic stenosis. Methods and Results-After macroscopic dissection of surgically removed human aortic valves, RNA was extracted from 311 preparations derived from 68 patients to differentiate normal, thickened, and calcified areas from each cusp. Subsequently, quantitative polymerase chain reaction analysis was used to correlate gene expression patterns with preoperative echocardiographic parameters. The messenger RNA levels of the LT-forming enzyme 5-lipoxygenase increased 1.6-and 2.2-fold in thickened and calcified tissue, respectively, compared with normal areas of the same valves. In thickened tissues, messenger RNA levels for Pϭ0.03), its activating protein (5-lipoxygenase activating protein; rϭϪ0.39; Pϭ0.02), and LTA 4 hydrolase (rϭϪ0.48; Pϭ0.01) correlated inversely with the velocity-time integral ratio. In addition, leukotriene A 4 hydrolase transcripts correlated inversely with aortic valve area, indexed for body surface area (rϭϪ0.52; Pϭ0.007). Immunohistochemical stainings revealed LT receptor expression on valvular myofibroblasts. In primary cultures of human myofibroblasts derived from stenotic aortic valves, Leukotriene C 4 (LTC 4 ) increased intracellular calcium, enhanced reactive oxygen species production, reduced the mitochondrial membrane potential, and led to morphological cell cytoplasm changes and calcification. Conclusions-The upregulation of the LT pathway in human aortic valve stenosis and its correlation with clinical stenosis severity, taken together with the potentially detrimental LT-induced effects on valvular myofibroblasts, suggests one possible role of inflammation in the development of aortic stenosis. (Circulation. 2011;123:1316-1325.)Key Words: aortic valve stenosis Ⅲ echocardiography Ⅲ inflammation Ⅲ leukotrienes Ⅲ myofibroblasts A lthough the primary risk factor for developing aortic stenosis is increasing age, 1 stenotic aortic valves share morphological characteristics with atherosclerotic lesions. For example, in the active disease process, lipid accumulation, 2 inflammatory infiltration, 3-5 neovascularization, 6,7 extracellular matrix degradation, 8 -10 and extensive calcification 3,5,11 take place, which eventually cause the aortic valve to narrow. However, attempts to inhibit the hemodynamic progression of aortic stenosis using lipid-lowering drugs have not been successful. [12][13][14] The poor prognosis and increased mortality from aortic stenosis after the onset of symptoms in the absence of surgical valve replacement 15 provide a rationale for the pursuit of a medical treatment that impedes the hemodynamic progression of aortic valve disease. Clinical Perspective on p 1325Inflammatory infiltration of activated macrophages and T-cells, as well as cytokine release, has been described in human s...

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“…Second, the nonspecific targeting to completely inhibit all activities of the leukotriene A 4 hydrolase enzyme may not be appropriate because of the unknown but potentially important biological contribution by the aminopeptidase activity of the enzyme. Taken together, it becomes apparent that significant confusion and knowledge gaps exist on this matter as a result of incomplete understanding of the biology of the aminopeptidase activity of the leukotriene A 4 [156] Fretland [144,157] Grespan [61] Sperling [19,65,158] Nielsen [159] Elmgreen [160] Smith [88,112] DiazGonzalez(BLTR) [113] Alten(BLTR) [114] Atherosclerosis Hagihara [161] Amsterdam [ …”

Section: The Possible Significance Of Leukotriene a 4 Hydrolase Aminomentioning

confidence: 99%