Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats

Nakamura, Kazufumi; Akagi, Satoshi; Ejiri, Kentaro; Yoshida, Masashi; Miyoshi, Toru; Sakaguchi, Masakiyo; Amioka, Naofumi; Suastika, Luh Oliva Saraswati; Kondo, Megumi; Nakayama, Rie; Takaya, Yoichi; Higashimoto, Yuichiro; Fukami, Kei; Matsubara, Hiromi; Ito, Hiroshi

doi:10.1016/j.jjcc.2020.12.009

Cited by 5 publications

(2 citation statements)

References 18 publications

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“…( 25 ) reported that AS-1, an inhibitor of RAGE signalling, suppressed the proliferation of smooth muscle cells of patients with idiopathic and heritable PAH, showing that inhibition of RAGE signalling may be a new therapeutic target for PAH. Also, a recent study demonstrated inhibitory effects of a short and single-stranded DNA directed against RAGE (RAGE aptamer) on the development of PAH in rats ( 35 ). This addresses a new therapeutic option for PAH which should be investigated in further studies.…”

Section: Discussionmentioning

confidence: 99%

The soluble receptor for advanced glycation end products is potentially predictive of pulmonary arterial hypertension in systemic sclerosis

et al. 2023

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IntroductionPulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are the leading causes of death in systemic sclerosis (SSc). Until now, no prospective biomarker to predict new onset of SSc-ILD or SSc-PAH in patients with SSc has reached clinical application. In homeostasis, the receptor for advanced glycation end products (RAGE) is expressed in lung tissue and involved in cell-matrix adhesion, proliferation and migration of alveolar epithelial cells, and remodeling of the pulmonary vasculature. Several studies have shown that sRAGE levels in serum and pulmonary tissue vary according to the type of lung-related complication. Therefore, we investigated levels of soluble RAGE (sRAGE) and its ligand high mobility group box 1 (HMGB1) in SSc and their abilities to predict SSc-related pulmonary complications.MethodsOne hundred eighty-eight SSc patients were followed retrospectively for the development of ILD, PAH, and mortality for 8 years. Levels of sRAGE and HMGB1 were measured in serum by ELISA. Kaplan-Meier survival curves were performed to predict lung events and mortality and event rates were compared with a log-rank test. Multiple linear regression analysis was performed to examine the association between sRAGE and important clinical determinants.ResultsAt baseline, levels of sRAGE were significantly higher in SSc-PAH-patients (median 4099.0 pg/ml [936.3-6365.3], p = 0.011) and lower in SSc-ILD-patients (735.0 pg/ml [IQR 525.5-1988.5], p = 0.001) compared to SSc patients without pulmonary involvement (1444.5 pg/ml [966.8-2276.0]). Levels of HMGB1 were not different between groups. After adjusting for age, gender, ILD, chronic obstructive pulmonary disease, anti-centromere antibodies, the presence of puffy fingers or sclerodactyly, use of immunosuppression, antifibrotic therapy, or glucocorticoids, and use of vasodilators, higher sRAGE levels remained independently associated with PAH. After a median follow-up of 50 months (25-81) of patients without pulmonary involvement, baseline sRAGE levels in the highest quartile were predictive of development of PAH (log-rank p = 0.01) and of PAH-related mortality (p = 0.001).ConclusionsHigh systemic sRAGE at baseline might be used as a prospective biomarker for patients with SSc at high risk to develop new onset of PAH. Moreover, high sRAGE levels could predict lower survival rates due to PAH in patients with SSc.

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Section: Discussionmentioning

confidence: 99%

The soluble receptor for advanced glycation end products is potentially predictive of pulmonary arterial hypertension in systemic sclerosis

et al. 2023

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“…Generally, many types of NPs have been used for drug-delivery systems, including calcium carbonate NPs, mesoporous silica NPs (MSNs), poly(lactic-co-glycolic acid) (PLGA) NPs, and lipid-based NPs. 47 , 48 However, these systems have limitations for clinical applications, such as hepatotoxicity caused by NP aggregation. In addition, these materials are foreign to the human body and may pose unknown risks for in vivo use, potentially causing side effects in normal cells.…”

Section: Discussionmentioning

confidence: 99%

A GD2-aptamer-mediated, self-assembling nanomedicine for targeted multiple treatments in neuroblastoma theranostics

Zhang

Wang

Zhu

et al. 2021

Molecular Therapy - Nucleic Acids

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Because current mainstream anti-glycolipid GD2 therapeutics for neuroblastoma (NB) have limitations, such as severe adverse effects, improved therapeutics are needed. In this study, we developed a GD2 aptamer (DB99) and constructed a GD2-aptamer-mediated multifunctional nanomedicine (ANM) with effective, precise, and biocompatible properties, which functioned both as chemotherapy and as gene therapy for NB. DB99 can bind to GD2 + NB tumor cells but has minimal cross-reactivity to GD2 − cells. Furthermore, ANM is formulated by self-assembly of synthetic aptamers DB99 and NB-specific MYCN small interfering RNA (siRNA), followed by self-loading of the chemotherapeutic agent doxorubicin (Dox). ANM is capable of specifically recognizing, binding, and internalizing GD2 + , but not GD2 − , NB tumor cells in vitro . Intracellular delivery of ANM activates Dox release for chemotherapy and MYCN-siRNA-induced MYCN silencing. ANM specifically targets, and selectively accumulates in, the GD2 + tumor site in vivo and further induces growth inhibition of GD2 + tumors in vivo ; in addition, ANM generates fewer or no side effects in healthy tissues, resulting in markedly longer survival with fewer adverse effects. These results suggest that the GD2-aptamer-mediated, targeted drug delivery system may have potential applications for precise treatment of NB.

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Hepatocyte Transplantation Rebalances Cytokines for Hepatic Regeneration in Rats with Ataxia Telangiectasia Mutated Pathway-Related Acute Liver Failure

Jaber¹,

Sharma²,

Gupta³

2023

The American Journal of Pathology

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Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats

Cited by 5 publications

References 18 publications

The soluble receptor for advanced glycation end products is potentially predictive of pulmonary arterial hypertension in systemic sclerosis

The soluble receptor for advanced glycation end products is potentially predictive of pulmonary arterial hypertension in systemic sclerosis

A GD2-aptamer-mediated, self-assembling nanomedicine for targeted multiple treatments in neuroblastoma theranostics

Hepatocyte Transplantation Rebalances Cytokines for Hepatic Regeneration in Rats with Ataxia Telangiectasia Mutated Pathway-Related Acute Liver Failure

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