LncPTSR Triggers Vascular Remodeling in Pulmonary Hypertension by Regulating [Ca<sup>2+</sup>]<sub>i</sub>in Pulmonary Arterial Smooth Muscle Cells

Deng, Liyu; Chen, Jidong; Chen, Bin; Wang, Ting; Yang, Lei; Liao, Jing; Yi, Junbo; Chen, Yuqin; Wang, Jian; Linneman, John; Niu, Yanqin; Gou, Deming

doi:10.1165/rcmb.2020-0480oc

Cited by 12 publications

(11 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although some studies have evaluated circRNAs in PAH, few have demonstrated the role of PDGF-BB-induced circRNAs in PAH. PDGF-BB is a potent mitogen that contributes to PVR [ 21 ]. PDGF-BB can accelerate the alteration of PASMCs from a quiescent state toward a proliferative and synthetic phenotype, which is a key causative factor in the occurrence and progression of PAH [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

CircItgb5 promotes synthetic phenotype of pulmonary artery smooth muscle cells via interacting with miR-96-5p and Uba1 in monocrotaline-induced pulmonary arterial hypertension

Zhu

et al. 2023

Respir Res

View full text Add to dashboard Cite

Background Pulmonary arterial hypertension (PAH) is a rare but fatal cardiopulmonary disease mainly characterized by pulmonary vascular remodeling. Aberrant expression of circRNAs has been reported to play a crucial role in pulmonary vascular remodeling. The existing literature predominantly centers on studies that examined the sponge mechanism of circRNAs. However, the mechanism of circRNAs in regulating PAH-related protein remains largely unknown. This study aimed to investigate the effect of circItgb5 on pulmonary vascular remodeling and the underlying functional mechanism. Materials and methods High-throughput circRNAs sequencing was used to detect circItgb5 expression in control and PDGF-BB-treated pulmonary arterial smooth muscle cells (PASMCs). Localization of circItgb5 in PASMCs was determined via the fluorescence in situ hybridization assay. Sanger sequencing was applied to analyze the circularization of Itgb5. The identification of proteins interacting with circItgb5 was achieved through a RNA pull-down assay. To assess the impact of circItgb5 on PASMCs proliferation, an EdU assay was employed. Additionally, the cell cycle of PASMCs was examined using a flow cytometry assay. Western blotting was used to detect biomarkers associated with the phenotypic switch of PASMCs. Furthermore, a monocrotaline (MCT)-induced PAH rat model was established to explore the effect of silencing circItgb5 on pulmonary vascular remodeling. Results CircItgb5 was significantly upregulated in PDGF-BB-treated PASMCs and was predominately localized in the cytoplasm of PASMCs. In vivo experiments revealed that the knockdown of circItgb5 attenuated MCT-induced pulmonary vascular remodeling and right ventricular hypertrophy. In vitro experiments revealed that circItgb5 promoted the transition of PASMCs to synthetic phenotype. Mechanistically, circItgb5 sponged miR-96-5p to increase mTOR level and interacted with Uba1 protein to activate the Ube2n/Mdm2/ACE2 pathway. Conclusions CircItgb5 promoted the transition of PASMCs to synthetic phenotype by interacting with miR-96-5p and Uba1 protein. Knockdown of circItgb5 mitigated pulmonary arterial pressure, pulmonary vascular remodeling and right ventricular hypertrophy. Overall, circItgb5 has the potential for application as a therapeutic target for PAH.

show abstract

Section: Discussionmentioning

confidence: 99%

CircItgb5 promotes synthetic phenotype of pulmonary artery smooth muscle cells via interacting with miR-96-5p and Uba1 in monocrotaline-induced pulmonary arterial hypertension

Zhu

et al. 2023

Respir Res

View full text Add to dashboard Cite

show abstract

“…Importantly, in vivo inhibition of LncPTSR by adenovirus associated virus type 9 (AAV9)-mediated shRNA in rats showed spontaneous development of PH, with increased right ventricular systolic pressure and pulmonary vascular remodeling in the normoxic condition, which suggest that lncPTSR is the key pathological factor during the development of PH. Mechanically, lncPTSR functioned as a cis -acting lncRNA to repress PMCA4 (plasma membrane calcium transporting ATPase 4) expression and attenuated the intracellular Ca 2+ efflux via the PDGF-BB mediated MEK/ERK signaling of PASMCs both in vitro and in vivo [ 107 ].…”

Section: Long Noncoding Rnas (Lncrnas) In Pulmonary Hypertensionmentioning

confidence: 99%

“…Apart from oligonucleotide-based RNA therapy, recombinant viral system can package shRNA into viral delivery tools to inhibit lncRNAs/circRNAs expression [ 167 , 168 ]. For example, adenovirus-associated virus type 9 (AAV9)-mediated shRNA LncPTSR in rats resulted in spontaneous development of the PH phenotype [ 107 ]. AAV5 and AAV9-mediated knockdown of circ-calm4 significantly prevented the development of PH in vivo [ 140 , 141 ].…”

Section: Ncrna Therapeuticsmentioning

confidence: 99%

The Landscape of Noncoding RNA in Pulmonary Hypertension

et al. 2022

View full text Add to dashboard Cite

The transcriptome of pulmonary hypertension (PH) is complex and highly genetically heterogeneous, with noncoding RNA transcripts playing crucial roles. The majority of RNAs in the noncoding transcriptome are long noncoding RNAs (lncRNAs) with less circular RNAs (circRNAs), which are two characteristics gaining increasing attention in the forefront of RNA research field. These noncoding transcripts (especially lncRNAs and circRNAs) exert important regulatory functions in PH and emerge as potential disease biomarkers and therapeutic targets. Recent technological advancements have established great momentum for discovery and functional characterization of ncRNAs, which include broad transcriptome sequencing such as bulk RNA-sequence, single-cell and spatial transcriptomics, and RNA-protein/RNA interactions. In this review, we summarize the current research on the classification, biogenesis, and the biological functions and molecular mechanisms of these noncoding RNAs (ncRNAs) involved in the pulmonary vascular remodeling in PH. Furthermore, we highlight the utility and challenges of using these ncRNAs as biomarkers and therapeutics in PH.

show abstract

“…8 The free calcium also helps to maintain vascular resistance at the vascular smooth muscles, which provide peripheral vascular resistance. 9 Regular exercise, body mass index control, weight loss, a diet rich in vegetables and natural products, and medication can all help to reduce hypertension-related mortality and morbidity. 10 The calcium channel blockers are used in the treatment of hypertension.…”

Section: Introductionmentioning

confidence: 99%

Estimation of Serum Calcium Level in the Patients of Hypertension

Ali¹,

Haque²,

Rauf³

et al. 2022

PJMHS

View full text Add to dashboard Cite

Background: Hypertension is one of the leading progressive cause of mortality and morbidity in developed as well as developing countries all over the world. Intracellular and extracellular ions of the body regulate the hemostasis of blood pressure. Objective: To estimate the serum calcium level in the patients of newly diagnosed cases of hypertension with normotensive set of subjects. Methodology: This case comparative study was conducted at the medical OPD of Bilawal Medical College and LUMHS Hospital Hyderabad and Jamshoro. 100 subjects were chosen and divided into two groups: 50 normotensive as a control group and 50 hypertensive as a case study group. Selection of samples was done on the basis of the non-probability technique. A sphygmomanometer was used to measure blood pressure, and a kit method was used to measure serum calcium levels. The statistical analysis of the data was carried out by SPSS version 22 by applying the student t test. Results: The mean age of control group subjects was 44 ± 6 years and control group was 42 ± 7 years. The mean systolic Blood pressure of control group was 110 ± 5 mmHg, while in case study group it was 140 ± 10 mmHg. The mean Diastolic blood pressure of control group was 80 ± 5 mmHg, while in case study group it was 105 ± 5 mmHg. The mean serum calcium level in control group was 9.82 ± 0.68 mg/dl and in case study group it was 8.45 ± 0.47 mg/dl. There was significant (p <0.05) difference of serum calcium level was observed in case study group (hypertensive subjects group). Conclusion: This study concluded that disturbance in intracellular calcium levels can be one of contributory factor in the pathogenesis of essential hypertension. Keywords: Essential Hypertension, Serum Calcium, Intracellular Calcium, Blood Pressure.

show abstract

LncPTSR Triggers Vascular Remodeling in Pulmonary Hypertension by Regulating [Ca²⁺]_iin Pulmonary Arterial Smooth Muscle Cells

Cited by 12 publications

References 46 publications

CircItgb5 promotes synthetic phenotype of pulmonary artery smooth muscle cells via interacting with miR-96-5p and Uba1 in monocrotaline-induced pulmonary arterial hypertension

CircItgb5 promotes synthetic phenotype of pulmonary artery smooth muscle cells via interacting with miR-96-5p and Uba1 in monocrotaline-induced pulmonary arterial hypertension

The Landscape of Noncoding RNA in Pulmonary Hypertension

Estimation of Serum Calcium Level in the Patients of Hypertension

Contact Info

Product

Resources

About

LncPTSR Triggers Vascular Remodeling in Pulmonary Hypertension by Regulating [Ca2+]iin Pulmonary Arterial Smooth Muscle Cells

Cited by 12 publications

References 46 publications

CircItgb5 promotes synthetic phenotype of pulmonary artery smooth muscle cells via interacting with miR-96-5p and Uba1 in monocrotaline-induced pulmonary arterial hypertension

CircItgb5 promotes synthetic phenotype of pulmonary artery smooth muscle cells via interacting with miR-96-5p and Uba1 in monocrotaline-induced pulmonary arterial hypertension

The Landscape of Noncoding RNA in Pulmonary Hypertension

Estimation of Serum Calcium Level in the Patients of Hypertension

Contact Info

Product

Resources

About

LncPTSR Triggers Vascular Remodeling in Pulmonary Hypertension by Regulating [Ca²⁺]_iin Pulmonary Arterial Smooth Muscle Cells