The role of Vascular Endothelial growth factor receptor-3 in the placenta in HIV associated preeclampsia.
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Summary: PE and HIV dualism in pregnant HAART women are yet to be investigated. Furthermore, the effect on VEGFR-3 and subsequent downstream influence on angiogenesis is poorly understood. Therefore, this investigation evaluates the immuno-expression of VEGFR-3 in placental conducting and exchange villi from normotensive, preeclamptic and HIV+ African women, using morphometric image analysis. Study design: This is a prospective study utilizing retrospectively collected, paraffin wax-embedded, placental samples (n=90) that were immuno-stained for VEGFR-3. The study population consisted of normotensive (n=30) and pre-eclamptic (n=60) groups which were further stratified on the basis of HIV status (negative - and positive +), and early and late onset preeclampsia (EOPE and LOPE respectively). The final groups were as follows; N- (n=15), N+ (n=15), EOPE- (n=15), EOPE+ (n=15), LOPE- (n=15) and LOPE+ (n=15). Brightfield microscopy and morphometric image analysis of VEGFR-3 immuno-expression within conducting and exchange placental villi was performed. Results: HIV status analysis did not demonstrate a significant difference in VEGFR-3 immunostaining for both villous types. The N vs. PE comparative analysis showed a downregulated immuno-expression of VEGFR-3 in both conducting (p = 0.0107) and exchange (p < 0.0001) villi. Results from analysis of pregnancy subtypes showed a significant difference in VEGFR-3 expression between N vs. EOPE regardless of villous type. Conclusion: This study demonstrates that HIV infection does not significantly alter VEGFR-3 placental immuno-expression in pregnant women receiving HAART irrespective of pregnancy type. Furthermore, VEGFR-3 immuno-expression was dysregulated in EOPE women, irrespective of HIV status. These novel findings emphasize severe down-regulation of VEGFR-3 in preeclamptic women, and provide compelling evidence for a future investigation into placental angiogenic and lymphangiogenic regulation in the early onset of PE. Isifinyezo: Inhlanganyela yePE neHIV kwabesifazane abakhulelwe abemukela iHAART kusamele kuphenywe. Ngakho-ke, lolu phenyo luhlola ukubonakaliswa kwe-VEGFR-3 kwiplacental ekuqhubeni nasekushintshaniseni i-villi kusuka ku-normotensive, preeclamptic ne-HIV+ kwabesifazane abansundu, kusetshenziswa ukuhlaziywa kwezithombe. Umklamo wokutadisha: Lokhu kucwaninga okungenzeka kusetshenziswa amasampula eplacental aqoqiwe, afakwe kwi-paraffin wax (n=90) abegcinelwe i-immuno-stain for VEGFR-3. Inani labantu abacwaningwayo liqukethe amaqembu: i-Normotensive (n=30) kanye ne-pre-eclamptic (n = 60) abephinde ahlukaniswa ngesisekelo sesimo se-HIV (abangenayo i-HIV Kanye nabanayo i-HIV+), kanye nabaqalwa yi-preeclampsia nalabo abakhombisa i-preeclamsia emva kwesikhathi eside (i-EOPE ne-LOPE) ngokulandelana. ). Amaqembu esewonke ngokulandelayo; N- (n=15), N+ (n=15), EOPE- (n=15), EOPE+ (n=15), LOPE- (n=15) no-LOPE+ (n=15). IBrightfield microscopy nokuhlaziywa kwezithombe imorphometric yeVEGFR-3 nokuziveza kwayo ngokuqhuba nokushintshaniswa kweplacental villie kwenziwa. Imiphumela: Ukuhlaziywa kwesimo seHIV akuvezanga umehluko omkhulu kwiVEGFR-3 immuno-staining kuzo zombili izinhlobo zeVillous. Ukuhlaziywa kokuqhathaniswa kwe-N vs. PE kukhombise ukubonakaliswa okuphansi kwe-immuno-expression kwe-VEGFR-3 kokubili kuqhuba (p = 0.0107) kanye nokushintshaniswa (p < 0.0001) villi. Imiphumela yokuhlaziywa kwezinhlobo ezahlukene zokukhulelwa zikhombise omkhulu umehluko ekubonisweni kweVEGFR-3 phakathi kwe N iqhathaniswa neEOPE kungakhathaleleki uhlobo lwevillous. Isiphetho: Lomkamo ukhombisa ukuthi ukutheleleka nge HIV akunawo umthelela omkhulu ekuvimbeni iVEGFR-3 immuno-expression kwabesifazane abakhulelwe abemukela iHAART kungakhathalaleki uhlobo lokukhulelwa. Ngaphezu kwalokho, iVEGFR-3 immuno-expression kwabesifazane abaneEOPE ayisebenzanga, kungakhathaleki isimo sabo seHIV. Okutholakale emibhalweni lugcozelela ngokukhulu ukwehla kwezinga kweVEGFR-3 kwabesifazane aba-preeclamptic, futhi kunikeza ubufakazi obuqanda ikhanda obungasetshenziswa kucwaningo oluzayo kweplacental angiogenic nelymphangiogenic regulation kulabo abaqedwa yiPE.