Plexiform vasculopathy of severe pulmonary arterial hypertension and microRNA expression

Bockmeyer, Clemens L.; Maegel, Lavinia; Janciauskiene, Sabina; Rische, Johanna; Lehmann, Ulrich; Maus, Ulrich A.; Nickel, Nils; Haverich, Axel; Hoeper, Marius M.; Golpon, Heiko; Kreipe, Hans; Laenger, Florian; Jonigk, Danny

doi:10.1016/j.healun.2012.03.010

Cited by 76 publications

(71 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although informative, this failure to tractably analyze tissues throughout the progression of human disease halts our insight into the molecular events that underpin the early stages of disease pathogenesis. In respect of this, and although existing literature strongly shows that miR-21 expression levels are induced in the lungs and pulmonary vessels of patients diagnosed with end-stage PH, 20,24 we cannot rule out the possibility that miR-21 is dynamically Figure 5. Pulmonary miR-21 induction in CAG-miR-21 mice inhibits programmed cell death 4 (PDCD4) induction and prevents the onset of pulmonary hypertension (PH) in vivo.…”

Section: Discussionmentioning

confidence: 79%

“…16,17 Appropriately, there is also an emergence of literature that connects miRNA biology and PH. [18][19][20][21][22][23][24][25] Among these, miR-21 is suggested as 1 candidate miRNA inherent to this molecular connection. Broadly, miR-21 levels are induced in murine and human pulmonary hypertensive tissues, 19,20 where it is assumed to protect against disease onset via beneficial repression of its direct target genes, including RhoB, 20 a well-defined molecular mediator of PH.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Endothelial Apoptosis in Pulmonary Hypertension Is Controlled by a microRNA/Programmed Cell Death 4/Caspase-3 Axis

et al. 2014

View full text Add to dashboard Cite

Abstract-Pulmonary endothelial cell apoptosis is a transient, yet defining pathogenic event integral to the onset of many pulmonary vascular diseases such as pulmonary hypertension (PH). However, there is a paucity of information concerning the molecular pathway(s) that control pulmonary arterial endothelial cell apoptosis. Here, we introduce a molecular axis that when functionally active seems to induce pulmonary arterial endothelial cell apoptosis in vitro and PH in vivo. In response to apoptotic stimuli, human pulmonary arterial endothelial cells exhibited robust induction of a programmed cell death 4 (PDCD4)/caspase-3/apoptotic pathway that was reversible by direct PDCD4 silencing. Indirectly, this pathway was also repressed by delivery of a microRNA-21 mimic. In vivo, genetic deletion of microRNA-21 in mice (miR-21 −/− mice) resulted in functional activation of the PDCD4/caspase-3 axis in the pulmonary tissues, leading to the onset of progressive PH. Conversely, microRNA-21-overexpressing mice (CAGmicroRNA-21 mice) exhibited reduced PDCD4 expression in pulmonary tissues and were partially resistant to PH in response to chronic hypoxia plus SU 5416 injury. Furthermore, direct PDCD4 knockout in mice (PDCD4 −/− mice) potently blocked pulmonary caspase-3 activation and the development of chronic hypoxia plus SU 5416 PH, confirming its importance in disease onset. Broadly, these findings support the existence of a microRNA-21-responsive PDCD4/ caspase-3 pathway in the pulmonary tissues that when active serves to promote endothelial apoptosis in vitro and PH

show abstract

Section: Discussionmentioning

confidence: 79%

mentioning

confidence: 99%

Endothelial Apoptosis in Pulmonary Hypertension Is Controlled by a microRNA/Programmed Cell Death 4/Caspase-3 Axis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Furthermore, miR-204 may be involved in vascular remodeling by regulating the proliferation and apoptosis of vascular smooth muscle cells (22). In addition, a number of other miRNAs have been associated with hypertension, including miR-296-5p, let-7e, miR-15b and miR-185, and their roles in regulating the development of hypertension require further investigation (23). The results of the present study demonstrated that miR-34a was significantly upregulated in patients with phase III hypertension compared with patients presenting with phase I and II hypertension, thus indicating that miR-34a may be closely associated with hypertension.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms in vascular injury induced by hypertension: Expression and role of microRNA‑34a

Liu

Cheng

et al. 2017

Exp Ther Med

View full text Add to dashboard Cite

Abstract. The aim of the present study was to investigate the expression and function of microRNA (miR)-34a in patients with primary hypertension. The expression of miR-34a was measured in the peripheral blood of 50 patients with primary hypertension and 28 normal controls by reverse transcription quantitative polymerase chain reaction. In addition, human umbilical vein endothelial cells (HUVECs) were transfected with an miR-34a inhibitor to suppress the expression of miR-34a, and the proliferation, migration and cell cycle distribution of HUVECs were measured by Cell Counting Kit-8, Transwell and flow cytometry assays. The target of miR-34a was also predicted by bioinformatics analysis and verified by a dual-luciferase reporter gene assay and western blot analysis. miR-34a was significantly upregulated in the peripheral blood of patients with hypertension when compared with controls (P<0.05), and upregulation of miR-34a was associated with a higher clinical stage of hypertension (phase III; P<0.05). In vitro experiments demonstrated that inhibition of miR-34a promoted the proliferation, migration and G1/S transition of HUVECs, relative to scramble-miR controls (P<0.05). Furthermore, transforming growth factor β-induced factor homeobox 2 (TIGF2) was predicted and verified to be a direct target of miR-34a. Collectively, these data suggested that miR-34a was upregulated in the peripheral blood of patients with hypertension, and that upregulated miR-34a may promote vascular endothelial injury by targeting TIGF2.

show abstract

“…Qin et al stated that miRNA-221 expression exposed to up-regulation in patients with asthma and that it could be a functional regulator for asthma pathogenesis [6]. Chen et al stated that miR-146a expression was down-regulated in the inflammatory process of pulmonary diseases, and Bockmeyer et al stated that there was an increase in miR-143/145 expression [12,16]. It was asserted that a decrease in miR-146a could be one of the determiners of inflammatory state and COPD progress.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of MicroRNAs in Chronic Obstructive Pulmonary Disease

Kara¹,

Kırkıl²,

Kalemci³

2015

Adv Clin Exp Med

View full text Add to dashboard Cite

Plexiform vasculopathy of severe pulmonary arterial hypertension and microRNA expression

Cited by 76 publications

References 33 publications

Endothelial Apoptosis in Pulmonary Hypertension Is Controlled by a microRNA/Programmed Cell Death 4/Caspase-3 Axis

Endothelial Apoptosis in Pulmonary Hypertension Is Controlled by a microRNA/Programmed Cell Death 4/Caspase-3 Axis

Molecular mechanisms in vascular injury induced by hypertension: Expression and role of microRNA‑34a

Differential Expression of MicroRNAs in Chronic Obstructive Pulmonary Disease

Contact Info

Product

Resources

About