No abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified previously in the pathogenesis of hypertension and some gestational diseases. However, the biological functions of MALAT1 in pregnancy-induced hypertension (PIH) are still poorly understood. Herein, we aim to explore the functional relevance of MALAT1 in PIH and to explain the potential underlying mechanisms. We found that the levels of ET-1 and MALAT1 were upregulated and that of miR-150-5p were downregulated in the serum of pregnant women with PIH and the aortic endothelial cells (ECs) of reduced uterine perfusion pressure (RUPP)-induced rat models. In aortic ECs, MALAT1 could competitively bind to miR-150-5p to upregulate the expression of ET-1. The MALAT1/ miR-150-5p/ET-1 axis regulated the expression of endothelin B receptor (ETBR) in aortic ECs leading to oxidative stress imbalance and increased the release of proinflammatory cytokines (IL-18 and IL-1β), which concurrently activated the NF-κB pathway to regulate the ETBR expression and to stimulate smooth muscle cell (SMC) contraction. Furthermore, silencing MALAT1 could alleviate the hypertensive symptoms of RUPP-induced rat models. Taken conjointly, the upregulation of MALAT1 can reduce the expression of ET-1 by competitively binding to miR-150-5p, which enhances the expression of ETBR via the activation of the NF-κB pathway in SMCs, thus exacerbating the hypertensive symptoms in the RUPP-induced rat models. K E Y W O R D Sendothelial cells, endothelin-1, metastasis-associated lung adenocarcinoma transcript 1, microRNA-150-5p, NF-κB pathway, pregnancy-induced hypertension, smooth muscle cells

The aim of this study was to investigate the effects and mechanisms of polyunsaturated fatty acids (PUFAs) and lipoxin A4 (LXA4) on preeclampsia (PE). The LXA4 level was significantly reduced in PE rats. The PUFA diet upregulated the expressions of lipoxygenase 12 (LOX12) and lipoxygenase 15 (LOX15) and downregulated those of cyclooxygenase-2, tumor necrosis factor-α (TNF-α), and endoglin. Lipopolysaccharides could inhibit cell growth and cause inflammatory response, while the presence of PUFAs inhibited the inflammatory response and promoted the expressions of LOX12, LOX15, and LXA4. Nordihydroguaiaretic acid (NDGA) regulated LXA4 expression and inflammation levels by affecting LOX. Inhibition of lipoxygenase 5 activity by NDGA upregulated the expressions of LOX12 and LOX15, while LXA4 reversed LXA4, nitric oxide downregulation, and TNF-α upregulation by NDGA. A decrease in LXA4 levels played an important role in the development and progression of PE.

Aims Recently, long non‐coding RNAs (lncRNAs) have been revealed to mediate smooth muscle dysfunction in thoracic aortic aneurysm (TAA). LncRNA HOXA‐AS2 has been proposed to engage in the regulation of diverse diseases. However, its function in TAA remains unknown. This study aimed to reveal the role and mechanism of HOXA‐AS2 in VSMCs which were implicated in TAA formation. Methods and results RT‐qPCR or western blot was performed to detect RNA or protein expression levels. The role of HOXA‐AS2 in VSMCs was explored by functional assays. The relationship among HOXA‐AS2/miR‐520d‐3p/KIAA1522/IGF2BP3 was analysed via mechanism assays. HOXA‐AS2 was detected to have significantly high expression in TAA tissues and function as an oncogene to promote proliferation of VSMCs, while inhibiting cell apoptosis (Figure 1, **P < 0.01). HOXA‐AS2 was unveiled to bind with miR‐520d‐3p (Figure 2, *P < 0.05, **P < 0.01) and further up‐regulate KIAA1522 to facilitate the growth of VSMCs (Figure 3–4, *P < 0.05, **P < 0.01). HOXA‐AS2 was also found to recruit IGF2BP3 to stabilize KIAA1522 mRNA (Figure 5, **P < 0.01). All data were displayed as mean ± standard deviation. Conclusions HOXA‐AS2 up‐regulates KIAA1522 through targeting miR‐520d‐3p/IGF2BP3 to drive VSMC growth in TAA.