Low molecular weight heparin-induced increase in chylomicron-remnants clearance, is associated with decreased plasma TNF-伪 level and increased hepatic lipase activity

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• 作者：Itamar Grosskopf^a ; ^b ; ^{itamar.grosskopf@sheba.health.gov.il" class="auth_mail} ; Aviv Shaish^a ; Assaf Ray^a ; ^b ; Dror Harats^a ; ^c ; Yehuda Kamari^a ; ^c
• 关键词：AUC ; area under the curve ; CAD ; coronary artery disease ; CM ; chylomicron ; CMR ; chylomicron remnants ; HL ; hepatic lipase ; hsCRP ; high sensitive C-reactive protein ; ISI ; insulin sensitivity index ; LDL ; low density lipoprotein ; LMWH ; low molecular weight heparin ; LPL ; lipoprotein lipase ; RP ; retinyl palmitate ; TNF-伪 ; tumor necrosis factor alpha ; TRL ; triglyceride rich lipoprotein ; VLDL ; very low density lipoprotein
• 刊名：Thrombosis Research
• 出版年：April, 2014
• 年：2014
• 卷：133
• 期：4
• 页码：688-692
• 全文大小：363 K

文摘

Objective

The acute effect of heparin on lipoprotein clearance is well characterized. Yet, the effect of prolonged low-molecular-weight-heparin (LMWH) administration on post-prandial lipemia has remained so far unexplored. Recent reports suggest that LMWH could modify lipid and carbohydrate metabolism by diminishing TNF伪-mediated inflammatory response. This, together with the known negative effect of TNF-伪 on insulin sensitivity, prompted us to hypothesize that LMWH would favorably affect post-prandial lipoprotein disposal.

Methods

Twenty four patients were given a vitamin A-fat loading meal at the end of 6-week enoxaparin treatment and after 3-month washout period. Post-prandial lipemia was assessed by measuring retinyl-palmitate (RP) during 8 hours following the meal. Insulin sensitivity index (ISI), plasma lipolytic activity and plasma TNF-伪 were measured.

Results

Enoxaparin did not impact fasting plasma lipids and lipoproteins levels. Enoxaparin increased RP clearance in the chylomicron remnant (CMR) fraction by 32% (P < 0.01). Additionally, enoxaparin decreased plasma TNF-伪 by 22% (P < 0.01), increased hepatic lipase (HL) activity by 81% (P < 0.01), along with a 2-fold increase in ISI (P < 0.01). The decrease in CMR correlated with the reduction in TNF伪 and the increase in ISI and HL activity (R = 0.48, -0.68, - 0.56, respectively, p < 0.05). Significant correlations were also found between the reduction in TNF伪 and both the increase in ISI and increase in HL activity (R = - 0.43, -0.54, respectively, P < 0.05).

Conclusions

The association of the effect on post-prandial metabolism, plasma TNF伪 level and HL activity during prolonged enoxaparin treatment may support the hypothesis that the beneficial outcome of enoxaparin may possibly be linked to anti-inflammatory and lipase-potentiating impact.