OS091. The origin of preeclampsia in diet-induced maternal endothelial stiffness

Despite research documenting variances in cellular hypoxia, angiogenesis, oxidative stress, endothelial signaling, and autoimmunity, the etiology of preeclampsia remains unknown. Women affected by preeclampsia show increased arterial stiffness and abnormal serum lipids when compared to unaffected mothers. Although enzymes modify and synthesize lipids, most acyl chains are incorporated into cell membranes unmodified from the form in which they were absorbed from the gastrointestinal tract. Therefore, diet plays a major role in determining the rheology and composition of cell membranes.

A-To present a model of how diet might alter cell membrane composition and cause increased maternal membrane viscosity when lipids are actively transported across the placenta to the fetus. B-To demonstrate how rapidly changing maternal membrane composition and viscosity might cause the pathological elements of preeclampsia.

Literature search.

Compared to diets of 10,000 years ago, modern diets have increased trans- and long-chain fatty acids, elevated omega-6 to -3 fatty acid ratios, and produce stiffer cell membranes, therefore might require increased membrane softening components such as cis-polyunsaturated fatty acids (PUFA) to maintain homeoviscosity. High fetal requirements for essential PUFAs might deplete body stores of these molecules in mothers with decreased dietary intake, thereby causing increased maternal membrane stiffness. Native proteins are only marginally stable under physiological conditions. A 2005 study using artificial membranes and the receptor rhodopsin, demonstrated that alteration of membrane lipid composition to increase membrane stiffness caused lower rhodopsin activation [1]. Increased membrane stiffness arising from dietary lipid variances might alter membrane proteins and cause the endothelial signaling dysfunction of preeclampsia. Although primary amino acid sequences remain unchanged, the disruption of tertiary protein structure might yield proteins that appear foreign and thus evoke an immune response, giving rise to antibodies such as agonistic autoantibody angiotensin-1. In mitochondria, disruption of electron transport protein structures might interfere with electron tunneling and increase the production of free radicals and oxidative stress. Because oxygen diffuses more rapidly through flexible versus stiff membranes,stiff cell membranes might initiate the signaling cascade indicative of cellular hypoxia in preeclampsia with increased hypoxia inducible factor and angiogenic factors such as soluble endoglin and fms-like tyrosine kinase. The arterial intima acts as a sensor with blood pressure homeostatic responses modulated by the flexibility of endothelial membranes. Similarly to a diaphragm pressure transducer, if the diaphragm material is stiff, the signal is attenuated; conversely, a flexible diaphragm makes the instrument more sensitive to pressure. Thus, stiffened endothelium might cause hypertension.

This paper presents a unifying molecular and cell membrane-based model of how diet-induced maternal cell membrane stiffness offers a coherent and unifying explanation for the pathological changes seen in preeclampsia.