The involvement of long noncoding RNA APOA1-AS in the pathogenesis of preeclampsia

Abstract

Objective Long noncoding RNAs (lncRNAs) are involved in preeclampsia (PE), and apolipoprotein A-1 antisense RNA (APOA1-AS) and has been found to be associated with a number of diseases. Our study aims to understand the involvement of APOA1-AS in PE. Methods Clinically, APOA1-AS expression in early-onset severe PE (EOSPE) patients and healthy controls was detected by real-time quantitative polymerase chain reaction. In vitro experiments were divided into control [coculturing trophoblasts with human uterine microvascular endothelial cells (UtMVECs)], TNF-α [coculturing trophoblasts with UtMVECs treated with tumor necrosis factor-α (TNF-α)], and TNF-α + control siRNA/APOA1-AS siRNA groups (UtMVECs transfected with control siRNA/APOA1-AS siRNA were cocultured with trophoblasts in the presence of TNF-α). The animals were divided into normal group, PE group (PE model was established by administrating nitro-L-arginine methyl ester (L-NAME) in rats), PE + control siRNA group (PE rats were treated with control siRNA), and PE + APOA1-AS siRNA group (PE rats were treated with APOA1-AS siRNA). Results Increased APOA1-AS was found in the placental tissues of EOSPE patients. APOA1-AS siRNA abolished the decreased integration of trophoblasts into UtMVEC networks induced by TNF-α. Furthermore, APOA1-AS siRNA improved pregnancy outcomes in PE rats with increased expression of vascular endothelial growth factor, placental growth factor, and fms-like tyrosine kinase receptor (Flt-1) but decreased expression of E-cadherin, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Conclusion Downregulation of APOA1-AS protected against TNF-α-induced inhibition of trophoblast integration into endothelial networks, thus exerting protective effects against PE rats.

APOA1 Is a Novel Marker for Preeclampsia

“…It has been reported that the expression of APOA1 was high in the blood and maternal-fetal interface during early miscarriages [17]. Additionally, evidence has revealed that apolipoprotein A-1 antisense RNA was increased in the placental tissues of early onset severe PE, and downregulation of APOA1-AS protected against TNFα-induced inhibition of trophoblast integration into endothelial networks, thus exerting protective effects against PE in rats [12]. This evidence indicates that the upregulation of APOA1 might indicate adverse pregnancy outcomes.…”

“…Apolipoprotein A1 (APOA1) is a major apoprotein constituent of high-density lipoproteins that plays important roles in tumor invasion and metastasis [10,11]. It has been reported that increased lncRNA APOA1-AS was found in the placental tissues of early onset severe PE, and downregulation of APOA1-AS protected against TNF-α-induced inhibition of trophoblast integration into endothelial networks, thus exerting protective effects in PE rats [12]. Recent findings have revealed the crucial roles of APOA1 in inflammation, tumor growth, angiogenesis, invasion, and metastasis [13][14][15].…”

Combined with dynamic serum proteomics and clinical follow-up to screen the serum proteins to promote the healing of diabetic foot ulcer

“…The subsequent protein interaction analysis showed that APOA1 was the key protein of DFU. It is believed that APOA1 may affect local coagulation, in ammation, angiogenesis, and wound repair [33][34][35].…”