Plasma cholesterol esterase level is a determinant for an atherogenic lipoprotein profile in normolipidemic human subjects

AbstractPlasma cholesterol level is controlled by various factors. In the present study, high plasma activity of cholesterol esterase was found to correlate with plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels in normolipidemic human subjects. However, the cholesterol esterase is not elevated in plasma of patients with familial hypercholesterolemia. These observations suggest that cholesterol esterase level is not determined by plasma cholesterol level, but elevated cholesterol esterase may be causative in increasing plasma cholesterol and LDL. Additional experiments further demonstrated that cholesterol esterase can convert the larger and less-atherogenic LDL to the smaller and more atherogenic LDL subspecies in vitro. These results suggest that plasma cholesterol esterase contributes to the formation and accumulation of atherogenic lipoproteins, and thus is a major risk factor for premature atherosclerosis in normal human subjects

Regulators of G protein signalling proteins in the human myometrium

The contractile state of the human myometrium is controlled by extracellular signals that promote relaxation or contraction. Many of these signals function through G proteincoupled receptors at the cell surface, stimulating heterotrimeric G proteins and leading to changes in the activity of effector proteins responsible for bringing about the response. G proteins can interact with multiple receptors and many different effectors and are key players in the response. Regulators of G protein signalling (RGS) proteins are GTPase activating proteins for heterotrimeric G proteins and help terminate the signal. Little is known about the function of RGS proteins in human myometrium and we have therefore analysed transcript levels for RGS proteins at various stages of pregnancy (non-pregnant, preterm, term non-labouring, term labouring). RGS2 and RGS5 were the most abundantly expressed isolates in each of the patient groups. The levels of RGS4 and RGS16 (and to a lesser extent RGS2 and RGS14) increased in term labouring samples relative to the other groups. Yeast two-hybrid analysis and co-immunoprecipitation in myometrial cells revealed that both RGS2 and RGS5 interact directly with the cytoplasmic tail of the oxytocin receptor, suggesting they might help regulate signalling through this receptor. Key words: G protein-coupled receptors; labour; myometrium; RGS protein

Alternative splicing: an important mechanism for myometrial gene regulation that can be manipulated to target specific genes associated with preterm labour

Considerable effort has been expended in attempting to distinguish genes that contribute to initiating the onset of term and preterm labour (PTL) from those that change in expression as a consequence of the progression of labour. The ability to define more clearly the genes involved in triggering labour contractions should lead to the development of new effective and safer strategies to prevent preterm birth. There is ample evidence to suggest that specific genes are co-ordinately regulated within the upper and lower regions of the myometrium prior to and during parturition and many of these genes are regulated by alternative pre-mRNA splicing. This mini-review highlights that expression of a range of different splicing factors, with defined roles in pre-mRNA splicing, is both temporally and spatially regulated within the uterine smooth muscle during pregnancy and labour. Moreover, several of these splicing factors play key roles in controlling the differential expression of specific regulatory proteins involved in uterine signalling and uterine quiescence. In addition, antisense morpholino oligonucleotide manipulation of pre-mRNA splicing may have potential in defining and targeting uterine pro-labour genes and thus contribute to the development of new therapeutic approaches to prevent PTL