Reduced PAF-acetylhydrolase activity associated with Lp(a) in patients with coronary artery disease

Tsironis, Loukas D.; Katsouras, Christos S.; Lourida, E.; Mitsios, John V.; Goudevenos, John; Elisaf, Moses; Tselepis, Alexandros D.

doi:10.1016/j.atherosclerosis.2004.07.030

Cited by 40 publications

(55 citation statements)

References 36 publications

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“…Several lines of evidences suggest that the mouse model, with a lipoprotein pro le di erent from humans, was inadequate for studying the e ects of Lp-PLA 2 inhibition in vi o because HDL-associated Lp-PLA 2 contributed to the reduction of atherosclerosis, whereas LDLassociated Lp-PLA 2 stimulated this process [6]. Controversy exists regarding this process, as increased plasma Lp-PLA 2 has also been associated with susceptibility to atherosclerosis in mice, and coronary heart disease patient exhibit reduced LDLLp-PLA 2 mass and catalytic e ciency, suggesting a diminished ability to degrade pro-in ammatory phospholipids [24,25]. Indeed the biological role of Lp-PLA 2 is controversial since the anti-or proatherogenic functions of this enzyme have been proposed.…”

Section: Discussionmentioning

confidence: 99%

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Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Zhang

Zhang²,

Sun³

et al. 2013

CIM

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Purpose: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the pathogenesis of atherosclerosis, especially in advanced plaques. In the present study, the abilities of darapladib, a selective Lp-PLA2 inhibitor, and lentivirus-mediated Lp-PLA2 silencing on in ammation and atherosclerosis in apolipoprotein E-de cient mice were compared.Methods: Apolipoprotein E-de cient mice were fed on a high-fat diet and a constrictive collar was placed around the le carotid artery to induce plaque formation. e mice were randomly divided into control, negative control (NC), darapladib and RNA interference (RNAi) groups. Eight weeks a er surgery, lentivirus-mediated RNAi construct or darapladib were used to decrease the expression of Lp-PLA2. Plaques were collected ve weeks later for histological analysis. In ammatory gene expression in the atherosclerotic lesions were then determined at the mRNA and protein level.Results: e expression of pro-in ammatory cytokines was signi cantly reduced in the treatment group, compared to nontreatment group, whereas the plasma concentration of anti-in ammatory cytokines increased markedly. Moreover, our results demonstrated a signi cant reduction in plaque lipid content, as well as a rise in collagen content following Lp-PLA2 inhibition. Interestingly, when comparing the two methods of Lp-PLA2 inhibition, animals treated with Lp-PLA2 RNAi were found to exhibit lower plaque areas and enhanced improvement of plaque stability as compared with animals treated with darapladib. Darapladib had no attenuating e ect on atherosclerotic plaque area. ese therapeutic e ects were independent of plasma lipoprotein levels.Conclusions: Lp-PLA2 inhibition by darapladib or lentivirus-mediated RNAi ameliorated in ammation and atherosclerosis in apolipoprotein E-de cient mice. e e ect was more prominent in the RNAi group.

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Section: Discussionmentioning

confidence: 99%

“…Indeed, no evidence that Lp-PLA 2 hydrolyze PAF in vi o was found in this study. Most research favors the pro-in ammatory and pro-atherogenic role of Lp-PLA 2 [24,25,30,31].…”

Section: Discussionmentioning

confidence: 99%

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Zhang

Zhang²,

Sun³

et al. 2013

CIM

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show abstract

“…Significantly increased 2-GPI-Lp(a) concentrations were also found in systemic lupus erythematosus (SLE) patients with excessive cardiovascular events and might act as an additional predictor of premature atherosclerosis 18) . It has also been reported that 2-GPI levels increase on isolated Lp(a) from CAD patients 19) ; therefore, we hypothesized that 2-GPI-Lp(a) may be associated with the presence and severity of CAD, and be a strong risk factor for atherosclerosis. Hence we designed this study to evaluate the clinical value of 2-GPI-Lp(a) levels in stable and unstable coronary syndromes.…”

Section: Introductionmentioning

confidence: 93%

Lipoprotein(a) Complexes with Beta2-Glycoprotein I in Patients with Coronary Artery Disease

Wang

Gong

et al. 2012

JAT

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“…The possibility that Lp(a) may become functionally altered in patients with coronary artery disease has been put forward by Tsironis on the basis of mass and specific activity of Lp(a) as mediator of platelet activating factor acetylhydrolase activity, an enzyme that hydrolyses oxidized phospholipids (24,25).…”

Section: Editorialmentioning

confidence: 99%

Reduction of cardiovascular risk in subjects with high lipoprotein (a) levels

et al. 2017

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Reduced PAF-acetylhydrolase activity associated with Lp(a) in patients with coronary artery disease

Cited by 40 publications

References 36 publications

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Lipoprotein(a) Complexes with Beta2-Glycoprotein I in Patients with Coronary Artery Disease

Reduction of cardiovascular risk in subjects with high lipoprotein (a) levels

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