The membrane protein CD36 has been reported to carry out a wide range of potential functions, including serving as a receptor for thrombospondin, collagen, oxidized low density lipoprotein, fatty acids, anionic phospholipids, and Plasmodium falciparum malaria parasitized erythrocytes. This implicates CD36 in cellular adhesion, human atherosclerotic lesion formation, lipid metabolism, and malaria. A presumed rat homolog of CD36 was previously reported to be palmitoylated. We confirmed that human CD36 is palmitoylated and identified cysteines 3, 7, 464, and 466 as the palmitoylation sites using a mutagenesis approach. This result suggests that both the N- and C-terminal tails of CD36 are cytoplasmic. Published models for the topology of CD36 have the C terminus located in the cytoplasm but differ as to whether the N terminus is cytoplasmic or extracellular. To address this question, a C-terminal truncation mutant of CD36 was made by introducing a stop codon just upstream of the C-terminal transmembrane domain. This mutant was found membrane-bound when expressed in human embryonic kidney 293 cells, indicating that the N-terminal hydrophobic domain serves as a transmembrane anchor, and thus supporting a CD36 topology with two transmembrane domains.

It is estimated that 10% of pregnancies are affected by hypertension worldwide. Approximately one-half of all hypertensive pregnancy disorders are due to preeclampsia, a pregnancy-specific disorder, its distinctive feature being either sudden onset, or worsening of pre-existing proteinuria. It has become increasingly recognized that women with a history of preeclampsia are at increased risk for future cardiovascular disease (CVD), but the mechanisms of this increase in risk are unclear. One possible explanation is that these two conditions share several common metabolic abnormalities as risk factors, including obesity, insulin resistance, and lipid abnormalities that may lead to preeclampsia and CVD at different times of a woman's life. Recent studies have revealed that, similar to CVD, several mediators of endothelial cell dysfunction are up-regulated in preeclampsia. Free radical derived oxidative stress, various inflammatory markers, including neutrophil response, C-reactive protein, and leukocyte adhesion, may contribute to endothelial dysfunction in both preeclampsia and coronary atherosclerosis. Alternatively, preeclampsia itself may induce metabolic and vascular changes that may increase the overall future risk for CVD in affected women. Therefore, at present, it remains unclear whether preeclampsia is a formal risk factor for CVD, or identifies women at increased risk for CVD later in life. Pending large-scale studies aiming to examine the causality of this association, women with a history of preeclampsia should be counseled regarding their increased risks for hypertension and other cardiovascular sequelae later in life, followed closely and treated aggressively for modifiable CVD risk factors.

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We conclude that down-regulation of nephrin and synaptopodin is associated with proteinuria in women with preeclampsia. Recent studies have demonstrated that soluble vascular endothelial growth factor receptor 1 (sFlt-1) levels are elevated in preeclampsia compared with normal pregnancy. Studies in mice have shown that sFlt-1 may play a role in inducing proteinuria by neutralizing vascular endothelial growth factor (VEGF) and suppressing nephrin. Proteinuria and elevations of sFlt-1 in preeclampsia are temporally related, further supporting a possible role of sFlt-1 in the dysregulation of podocyte foot-process proteins.