京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20987号 / 医博第4333号 / 新制||医||1027(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 長船 健二, 教授 一山 智 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

<p>Biochemical and epidemiological aspects of pre-eclampsia were investigated, with the main focus on possible pathophysiological differences between early-onset and late-onset disease.</p><p>In pre-eclamptic women poor correlation was found between albumin-creatinine ratio (ACR) in a random urine sample and total amount of albumin in a 24-hour urine collection. <i>(Paper I)</i><b> </b></p><p>In a cohort of women giving birth in Sweden in 1973-82 we estimated the adjusted incidence rate ratio (IRR) for ischaemic heart disease (IHD) during the years 1987–2001. The adjusted IRR for development of IHD was 1.6-2.8 in woman exposed to gestational hypertensive disease during her pregnancy compared with unexposed women. The higher risk represents more severe or recurrent hypertensive disease. <i>(Paper II)</i></p><p>Before delivery, in early-onset pre-eclampsia (24-32 weeks) there were pronounced alterations in plasma concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), and also a higher placental 8-iso-PGF_2α concentration and an elevated serum ratio of plasminogen-activator inhibitor (PAI)-1 to PAI-2 compared with early controls. In late-onset pre-eclampsia (35-42 weeks) there were only moderate alterations in sFlt1 and PlGF concentrations, and the placental 8-iso-PGF_2α concentration and PAI-1/ PAI-2 ratio were similar to those in late controls. <i>(Papers III, V)</i> There was a rapid postpartum decrease in sFlt1 concentration in all groups. One week postpartum the sFlt1 concentration was persistently higher, however, in women with early-onset pre-eclampsia compared with early controls. <i>(Paper IV)</i></p><p>In conclusion: random ACR cannot replace 24-hour urine collections for quantification of albuminuria in pre-eclamptic women; gestational hypertensive disease, especially severe or recurrent, increases the risk for later IHD; early-onset, but not late-onset pre-eclampsia is associated with pronounced alterations of angiogenesis-related markers and only early-onset pre-eclampsia is associated with placental oxidative stress and an increased PAI-1/ PAI-2 ratio, all suggesting a stronger link between early-onset than late-onset pre-eclampsia and a dysfunctional placenta.</p>

Biochemical and epidemiological aspects of pre-eclampsia were investigated, with the main focus on possible pathophysiological differences between early-onset and late-onset disease. In pre-eclamptic women poor correlation was found between albumin-creatinine ratio (ACR) in a random urine sample and total amount of albumin in a 24-hour urine collection. (Paper I)<b> </b> In a cohort of women giving birth in Sweden in 1973-82 we estimated the adjusted incidence rate ratio (IRR) for ischaemic heart disease (IHD) during the years 1987–2001. The adjusted IRR for development of IHD was 1.6-2.8 in woman exposed to gestational hypertensive disease during her pregnancy compared with unexposed women. The higher risk represents more severe or recurrent hypertensive disease. (Paper II) Before delivery, in early-onset pre-eclampsia (24-32 weeks) there were pronounced alterations in plasma concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), and also a higher placental 8-iso-PGF2α concentration and an elevated serum ratio of plasminogen-activator inhibitor (PAI)-1 to PAI-2 compared with early controls. In late-onset pre-eclampsia (35-42 weeks) there were only moderate alterations in sFlt1 and PlGF concentrations, and the placental 8-iso-PGF2α concentration and PAI-1/ PAI-2 ratio were similar to those in late controls. (Papers III, V) There was a rapid postpartum decrease in sFlt1 concentration in all groups. One week postpartum the sFlt1 concentration was persistently higher, however, in women with early-onset pre-eclampsia compared with early controls. (Paper IV) In conclusion: random ACR cannot replace 24-hour urine collections for quantification of albuminuria in pre-eclamptic women; gestational hypertensive disease, especially severe or recurrent, increases the risk for later IHD; early-onset, but not late-onset pre-eclampsia is associated with pronounced alterations of angiogenesis-related markers and only early-onset pre-eclampsia is associated with placental oxidative stress and an increased PAI-1/ PAI-2 ratio, all suggesting a stronger link between early-onset than late-onset pre-eclampsia and a dysfunctional placenta.