Transcriptomics of angiotensin II-induced long noncoding and coding RNAs in endothelial cells

Bu, Shuhan; Nguyen, Hien; Michels, David; Rasheed, Berk; Nikfarjam, Sepideh; Singh, Rohan; Wang, Lynn; Patel, Darshil A; Singh, Shweta; Qadura, Mohammad; Singh, Krishna K.

doi:10.1097/hjh.0000000000003140

Cited by 5 publications

(4 citation statements)

References 80 publications

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“…The prevalence of HF has reached 20% at the age of 40, and the incidence increases with age [30]. Previous studies have reported that many aberrantly expressed lncRNAs play a critical role in the pathogenesis and progression of cardiac hypertrophy and myocardial injury [31][32][33]. Yang et al reported that the lncRNA MIAT could affect the handling of calcium and contractile function, resulting in cardiac myocyte remodelling and hypertrophy [11].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of lncRNA Expression Pattern and Potential Role in Heart Failure Pathology

Chen,

Shi,

Gao

et al. 2023

Disease Markers

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During the last few decades, the morbidity and mortality of heart failure (HF) have remained on an upward trend. Despite the advances in therapeutic and diagnostic measures, there are still many aspects requiring further research. This study is aimed at finding potential long noncoding RNAs (lncRNAs) that could aid with the diagnosis and treatment of HF. We performed RNA sequencing on the peripheral blood of healthy controls as well as HF patients. The expression of lncRNAs was validated by RT-qPCR. Bioinformatic analysis was performed to investigate the possible mechanism of differentially expressed lncRNAs and mRNAs. The diagnostic value of lncRNAs was analysed by ROC analysis. Finally, a total of 207 mRNAs and 422 lncRNAs were identified. GO and KEGG pathway analyses revealed that biological pathways such as immune response, regulation of cell membrane, and transcriptional regulatory process were associated with the pathological progress of HF. The lncRNA-mRNA coexpression network was conducted, and several mRNAs were identified as key potential pathological targets, while lncRNA CHST11, MIR29B2CHG, CR381653.1, and FP236383.2 presented a potential diagnostic value for HF. These findings provide novel insights for the underlying mechanisms and possible therapeutic targets for HF.

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Section: Discussionmentioning

confidence: 99%

Evaluation of lncRNA Expression Pattern and Potential Role in Heart Failure Pathology

Chen,

Shi,

Gao

et al. 2023

Disease Markers

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“…Endothelial cells line the innermost layer of blood vessels and have critical roles in maintaining vascular homeostasis [1]. Imbalanced autophagy can lead to endothelial dysfunction and cardiovascular diseases [2][3][4][5][6]. Autophagy is a tightly regulated process in endothelial cells, and its genetic and epigenetic regulation is well established [3].…”

Section: Introductionmentioning

confidence: 99%

Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival

Bu,

Singh,

Nguyen

et al. 2024

IJMS

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Endothelial autophagy plays an important role in the regulation of endothelial function. The inhibition of endothelial autophagy is associated with the reduced expression of protein disulfide isomerase 4 (PDIA-4); however, its role in endothelial cells is not known. Here, we report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked changes in endothelial cell architecture, accompanied by the loss of endothelial markers and the gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition (EndMT). The loss of PDIA-4 activated TGFβ-signaling, and inhibition of TGFβ-signaling suppressed EndMT in PDIA-4- silenced endothelial cells in vitro. Our findings help elucidate the role of PDIA-4 in endothelial autophagy and endothelial function and provide a potential target to modulate endothelial function and/or limit autophagy and EndMT in (patho-)physiological conditions.

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“…AK098656-transgenic rats developed spontaneous hypertension, with increased VSMC synthetic phenotype and narrowed resistant arteries [ 19 ]. On the other hand, studies have also shown that AngII can regulate lncRNAs in ECs, which may, in turn, modulate EC viability, apoptosis, and migration [ 20 , 21 ]. However, it is not yet known whether the perturbation of an endothelial lncRNA can impact BP.…”

Section: Introductionmentioning

confidence: 99%

Genetic Deletion of the LINC00520 Homolog in Mouse Aggravates Angiotensin II-Induced Hypertension

Tang

Lai

Malhi

et al. 2023

ncRNA

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(1) Background: Hypertension is a complex, multifactorial disease that is caused by genetic and environmental factors. Apart from genetic predisposition, the mechanisms involved in this disease have yet to be fully understood. We previously reported that LEENE (lncRNA enhancing endothelial nitric oxide expression, transcribed from LINC00520 in the human genome) regulates endothelial cell (EC) function by promoting the expression of endothelial nitric oxide synthase (eNOS) and vascular growth factor receptor 2 (VEGFR2). Mice with genetic deletion of the LEENE/LINC00520 homologous region exhibited impaired angiogenesis and tissue regeneration in a diabetic hindlimb ischemia model. However, the role of LEENE in blood pressure regulation is unknown. (2) Methods: We subjected mice with genetic ablation of leene and wild-type littermates to Angiotensin II (AngII) and monitored their blood pressure and examined their hearts and kidneys. We used RNA-sequencing to identify potential leene-regulated molecular pathways in ECs that contributed to the observed phenotype. We further performed in vitro experiments with murine and human ECs and ex vivo experiments with murine aortic rings to validate the select mechanism. (3) Results: We identified an exacerbated hypertensive phenotype of leene-KO mice in the AngII model, evidenced by higher systolic and diastolic blood pressure. At the organ level, we observed aggravated hypertrophy and fibrosis in the heart and kidney. Moreover, the overexpression of human LEENE RNA, in part, restored the signaling pathways impaired by leene deletion in murine ECs. Additionally, Axitinib, a tyrosine kinase inhibitor that selectively inhibits VEGFR suppresses LEENE in human ECs. (4) Conclusions: Our study suggests LEENE as a potential regulator in blood pressure control, possibly through its function in ECs.

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Transcriptomics of angiotensin II-induced long noncoding and coding RNAs in endothelial cells

Cited by 5 publications

References 80 publications

Evaluation of lncRNA Expression Pattern and Potential Role in Heart Failure Pathology

Evaluation of lncRNA Expression Pattern and Potential Role in Heart Failure Pathology

Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival

Genetic Deletion of the LINC00520 Homolog in Mouse Aggravates Angiotensin II-Induced Hypertension

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