Placenta growth factor and sFlt-1 as biomarkers in ischemic heart disease and heart failure: a review.

Coronary heart disease (CHD) and heart failure (HF) produce significant morbidity/mortality but identifying new biomarkers could help in the management of each. In this article, we summarize the molecular regulation and biomarker potential of PIGF and sFlt-1 in CHD and HF. PlGF is elevated during ischemia and some studies have shown PlGF, sFlt-1 or PlGF:sFlt-1 ratio, when used in combination with standard biomarkers, strengthens predictions of outcomes.

An Industrial Engineering Approach to Cost Containment of Pharmacy Education.

A 2-semester project explored employing teams of fourth-year industrial engineering students to optimize some of our academic management processes. Results included significant cost savings and increases in efficiency, effectiveness, and student and faculty satisfaction. While we did not adopt all of the students' recommendations, we did learn some important lessons.

XIAP protein is induced by placenta growth factor (PLGF) and decreased during preeclampsia in trophoblast cells.

Increased trophoblast apoptosis has been implicated in pregnancies complicated by fetal growth restriction and preeclampsia (EC). We investigated placenta growth factor (PLGF) signaling during trophoblast apoptosis in culture and X-linked inhibitor of apoptosis protein (XIAP) and apoptosis inducible factor (AIF) in the preeclamptic placenta at term was determined. Primary trophoblasts were isolated and serum starved to induce apoptosis.

Nitric oxide generation affects pro- and anti-angiogenic growth factor expression in primary human trophoblast.

Objectives: Preeclampsia is associated with reduced trophoblast placenta growth factor (PGF) expression, elevated soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased bioactivity of nitric oxide (NO). Elevated sFlt-1 reduces bio-availability of PGF and vascular endothelial growth factor (VEGF) leading to maternal endothelial dysfunction. Although NO can regulate gene expression, its ability to regulate trophoblast expression of angiogenic growth factors is not known.

Dysregulation of promyelocytic leukemia (PML) protein expression in preeclamptic placentae.

Promyelocytic leukemia (PML) protein is a nucleoprotein that can regulate a variety of cellular stress responses. The aim of this study was to determine qualitative and quantitative changes in PML expression in preeclamptic placentae. Immunoblot, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and immunohistochemistry techniques were used to determine PML gene expression and localization in normal (n = 6) and preeclamptic (n = 6) placentae and primary cells.

Differential regulation of human PlGF gene expression in trophoblast and nontrophoblast cells by oxygen tension.

Objective: To determine the mechanism for differential effects of low oxygen tension on human PlGF gene transcription in trophoblast and nontrophoblast cells.

Study Design: Human PlGF reporter clones and real-time RT-PCR were used to compare the effects of hypoxia on gene transcription in human trophoblast and nontrophoblast cell lines. Overexpression of HIF-1alpha, inhibition of HIF-1 function and biochemical assessments of HIF-1 co-factor interactions were used to characterize hypoxia response mechanisms regulating PlGF transcription.

Hypoxia increases placenta growth factor expression in human myocardium and cultured neonatal rat cardiomyocytes.

Background: Placenta growth factor (PlGF) plays an important role in pathologic angiogenesis and is believed to be an independent biomarker in patients with coronary artery disease. However, little is known regarding the regulation of PlGF expression in heart tissue.

Methods: We determined expression changes in PlGF and its receptor, VEGFR1, in normal and abnormal biopsies from human cardiac allografts and in cardiomyocytes cultured under hypoxia or cyclical stretch conditions.

Glial cell missing 1 regulates placental growth factor (PGF) gene transcription in human trophoblast.

Placental growth factor (PGF, previously known as PlGF) is prominently expressed by trophoblasts in human placenta, whereas most nontrophoblast cells express low levels of PGF mRNA under normal physiological conditions. We have shown that hypoxia decreases PGF expression in the trophoblast, but little is known about transcriptional regulation of PGF gene expression. We sought to determine promoter regions of the human PGF gene that contribute to its restricted high constitutive expression in the trophoblast.

Angiogenesis in implantation.

Problem: Implantation failure and early pregnancy loss are common following natural conceptions and they are particularly important clinical hurdles to overcome following assisted reproduction attempts. The importance of adequate vascular development and maintenance during implantation has recently become a major focus of investigation.

Materials And Methods: Review of current published literature was undertaken to summerize the cells and cell products that regulate tissue vascularity during implantation.

Determinants of placental vascularity.

Problem: Vascular growth during implantation and placentation is critical for successful gestation and it is thought that vascular insufficiencies during placentation contribute to a number of obstetrical complications. However, relatively little is known regarding the regulation of angiogenesis in the placenta.

Method Of Study: We review literature concerning the potential significance of inadequate placental vascularity as a contributor to the obstetrical complications of spontaneous abortion, fetal growth restriction and preeclampsia.

Deferential regulation of placenta growth factor (PlGF)-mediated signal transduction in human primary term trophoblast and endothelial cells.

Increasing evidence supports that many common obstetrical complications may involve the disruption of normal placental and/or uterine vascular function. Placenta growth factor (PlGF) is an angiogenic factor that is abundantly expressed in the placenta, with primary site of synthesis being trophoblast. Receptors for PlGF include products of the fms-like tyrosine kinase (flt-1) gene which is expressed in several cell types including endothelial cells and trophoblast.

Altered expression of vascular endothelial growth factor and its receptors in normal saphenous vein and in arterialized and stenotic vein grafts.

Background: Myointimal thickening is a major cause saphenous vein graft failure. The prominence of medial and adventitial microvessels in stenotic vein grafts and the known angiogenic effects of vascular endothelial growth factor (VEGF) lead us to investigate the expression of VEGF and its receptors in vein graft arterialization and stenosis.

Methods: Normal and arterialized vein graft segments were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) for expression of VEGF-R1 (flt), VEGF-R2 (KDR), and neuropilin-1.

Evidence of a novel isoform of placenta growth factor (PlGF-4) expressed in human trophoblast and endothelial cells.

Placenta growth factor (PlGF), a homodimeric glycoprotein that is homologous to vascular endothelial growth factor (VEGF), is mitogenic to endothelial cells and protects trophoblast from apoptosis. Alternative splicing of mature mRNA gives rise to three known isoforms of PlGF. PlGF is expressed by human trophoblast during normal pregnancy, however, it is not known which isoforms are produced.

Expression and function of placenta growth factor: implications for abnormal placentation.

Objective: Essential requirements for successful gestation include the coordinated growth and differentiation of the placenta and the development of a functional placental vasculature. However, relatively little is known about factors that are responsible for regulating these functions. One angiogenic growth factor that might be involved in regulating both vascular endothelial cell and trophoblast function is placental growth factor (PGF).

Low maternal serum levels of placenta growth factor as an antecedent of clinical preeclampsia.

Objective: Maternal serum placenta growth factor levels have been shown to be significantly reduced in women with established preeclampsia. However, the temporal change in serum placenta growth factor levels before the clinical onset of preeclampsia is not known.

Study Design: Serum samples were collected from patients at the first prenatal (5-15 weeks' gestation), second-trimester (16-20 weeks' gestation), and third-trimester (26-30 weeks' gestation) visits.

Vascular antithrombin and clinical outcome in heart transplant patients.

A procoagulant microvasculature is associated with accelerated development of coronary artery disease (CAD) and failure in heart transplant patients. This study was performed to evaluate how changes in natural anticoagulation within cardiac allografts affect outcome. We prospectively studied 141 consecutive cardiac allograft recipients who underwent transplantation between 1988 and 1997.

Increased vascular endothelial growth factor expression in human hearts with microvascular fibrin.

We have shown that microvascular changes that promote fibrin deposition in human cardiac allografts adversely affect clinical outcome. However, some allografts exhibit phenotypic changes in capillaries following the deposition of fibrin, which subsequently provide a significant survival advantage. The mechanism(s) involved in these capillary changes is(are) unknown.

Risk of early renal allograft failure is increased for patients with antiphospholipid antibodies.

Renal allograft thrombosis can cause transplant failure. Because antiphospholipid antibodies (aPA) are associated with thrombosis, we investigated pretransplant sera from patients with early renal allograft failure to determine if aPA were present. Fifty-six final cross-match (FxM) sera from patients whose transplant failed within 16 days were compared to FxM sera from the next sequential transplant patients.

Antibodies to endothelial cells identify myocardial damage and predict development of coronary artery disease in patients with transplanted hearts.

Background: Transplant-induced coronary artery disease is a leading cause of graft failure in cardiac allograft recipients after the first year of transplantation, but there presently is no test to identify patients at high risk for developing the disease. Our research is focused on development of a predictive test to identify patients at high risk of developing the disease.

Methods: Sixty-eight cardiac allograft recipients transplanted and followed at Methodist Hospital between 1982 and 1996 were studied.

Placenta growth factor: potential role in pregnancy.

Problem: In spite of the known requirement for adequate vascularity during placentation, little is known regarding the regulation of angiogenic growth factor production by trophoblast. Placenta growth factor (PIGF) is a recently discovered angiogenic growth factor whose expression is relatively limited to trophoblast.

Method Of Study: Current literature of PIGF was reviewed, with emphasis on its expression, regulation, role in angiogenesis, and potential function(s) at the maternal-fetal interface.