Biomedical subjects

Ronald J Torry

Publications and source records attributed to Ronald J Torry.

4 recordsLinked to original sources

PubMed2004

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. Gene expression assays were used to compare fluctuations of placenta growth factor (PlGF) and PlGF receptor expression in normal and preeclamptic trophoblast in vitro. RESULTS: Studies have shown that common obstetrical complications manifest altered placental vascularity. Both intrinsic defects (gene knockouts) and extrinsic factors (O(2) tension, cytokines, etc) may be responsible for the defects. Some of these factors have been shown to influence trophoblast vascular endothelial growth factor (VEGF)/PlGF expression suggesting this particular family of angiogenic proteins play an important role in placental angiogenesis. CONCLUSION: Placental vascularization reflects a complex interaction of regulatory factors. Understanding the regulation of vascular growth in the placenta will provide much needed insight into placenta-related vascular insufficiencies.

Abortion, Spontaneous↗

PubMed2003

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. The cells expressing VEGF, VEGF-R1, VEGF-R2, and neuropilin-1 were identified in normal, stenotic, and arterialized vein graft segments by immunohistochemistry. RESULTS: Vascular endothelial growth factor, detected in the wall in endothelial cells and adventitial microvessels in normal vein, localized to smooth muscle cells, endothelial cells and adventitial microvessels in arterialized and stenotic vein. VEGF-R1 and VEGF-R2 were expressed infrequently on endothelial cells, macrophages, and smooth muscle cells in arterialized and stenotic vein. Neuropilin-1 was detected in all specimens. RT-PCR demonstrated significantly greater expression of neuropilin-1 in normal vein compared with arterialized vein (P <0.05). CONCLUSIONS: The differential expression of VEGF and its receptors in normal, arterialized, and stenotic vein grafts suggests that alterations in VEGF/VEGF-R2/neuropilin-1 interactions may be important determinants of the adaptive response of vein grafts to arterialization.

Graft Occlusion, Vascular↗

PubMed2003

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. We have utilized RT-PCR to characterize PlGF isoform expression in normal human trophoblast and umbilical vein endothelial cells (HUVEC). Our results show that PlGF-1, PlGF-2, and PlGF-3 isoforms are expressed by trophoblast and HUVECs. In addition, both cell types also express a novel variant of PlGF, tentatively termed PlGF-4, which has not been previously reported. PlGF-4 consists of the same sequence of PlGF-3, plus the heparin binding domain previously thought to be present only in PlGF-2. Presence of the heparin binding domain in PlGF-4 suggests that this variant would remain cell membrane-associated and thus could influence trophoblast and endothelial cells in an autocrine manner.

Alternative Splicing↗

PubMed2003

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). METHODS: Current published reports were surveyed and our own work was reviewed to highlight the expression, function, and potential significance of PGF at the human maternal-fetal interface. RESULTS: PGF is highly expressed in trophoblasts during normal pregnancy, and its expression is significantly decreased in preeclampsia, an obstetric complication presumed to be associated with placental bed hypoxia and ischemia. In agreement with this, in vitro trophoblast expression of PGF can be down-regulated by low oxygen tension. The cognate receptor for PGF, fms-like tyrosine kinase receptor, is expressed on trophoblasts as well as vascular endothelial cells, suggesting that it has autocrine and paracrine functions. Accordingly, PGF can regulate proliferation in first trimester trophoblasts, apoptosis in term trophoblasts, and it can directly or indirectly regulate vascular growth, maturation, and permeability. CONCLUSIONS: Many obstetric complications, most notably preeclampsia, are associated with aberrant trophoblast function and inadequate or dysfunctional vasculature within the developing placenta. The ability of PGF to influence trophoblast and vascular endothelial cells provides clear impetus for further studies to investigate the biological and clinical significance of PGF in normal and abnormal human pregnancies.

Animals↗