Plasma lipids and vascular dysfunction in preeclampsia

The dominating hypothesis of the preeclampsia syndrome (PES) is that placen tally derived factors are released to the maternal circulation. These facto rs are believed to alter endothelial properties resulting in disturbed vaso motor function, increased endothelial permeability, and activation of throm bogenic factors. However, the impact of placentally derived factors on the endothelial cells is influenced by another major variable: the "sensitivity " of the maternal endothelium to the placental factors. Several maternal fa ctors may play a role in determining this sensitivity. They include chronic hypertension, diabetes, and hyperlipidemia. In this article We discuss the possible role of hyperlipidemia (especially high free fatty acids and hype rtriglyceridemia) in the pathogenesis of preeclampsia, viewed from this per spective. Pregnancy in general, preeclamptic pregnancy in particular is associated wi th a marked hyperlipidemia. We suggest a parallel to atherosclerotic diseas es, wherein hyperlipidemia induces endothelial dysfunction, probably by pro moting oxidative stress in the arterial wall. The hyperlipidemia of pregnan cy may have a similar effect on the endothelial cells. When placentally der ived endothelial disturbing factors, like lipid peroxides and trophoblastic components, are released into the maternal circulation, their effects on t he endothelium may be enhanced because of hyperlipidemia-mediated activatio n or "sensitization" of the endothelial cells. Alternatively, placentally d erived factors like peroxides may combine with lipoproteins, forming comple x:es that are more disturbing to cells than the placental factors or lipopr oteins are individually We also discuss the possible role of maternal hyperlipidemia in aggravating placental insufficiency caused by poorly transformed spiral arteries. The hemodynamic flow pattern may be markedly different in completely and incomp letely transformed spiral arteries. By analogy to the fundamental role of h emodynamic factors in development of atherosclerosis, we pose the hypothesi s that abnormally transformed spiral arteries have an "atherogenic" bloodfl ow pattern that promotes lipid deposition and "acute atherosis."