A systematic review with meta-analysis of biomarkers for detection of pulmonary arterial hypertension

Smits, Josien; Botros, Liza; Mol, M.A.E.; Ziesemer, Kirsten A.; Wilkins, Martin R.; Vonk‐Noordegraaf, Anton; Bogaard, Harm Jan; Aman, Jurjan

doi:10.1183/23120541.00009-2022

Cited by 12 publications

(8 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…В исследовании Huang et al, 2022 приведены аналогичные данные по отрицательной коррелляции уровня общего холестерина, ХС ЛПНП и систолического давления в ЛА, а также в целом более низком уровне ХС ЛПНП у пациентов с ЛАГ и системной красной волчанкой [58]. Возможные причины более низкого уровня ХС ЛПНП при ЛАГ -хроническое воспаление, сниженное питание, нарушение синтетической функции печени [59].…”

Section: нарушение липидного обменаunclassified

“…В метаанализе 2022 года (включено 6 исследований пациентов с ЛАГ, получающих ЛАГ-специфическую терапию), у пациентов с ЛАГ определялись более низкие уров-ни ХС ЛПНП: −15,82 мг/дл (95%ДИ −26,18-−5,46, p<0,00001) по сравнению с контрольной группой [59]. ХС ЛПНП не имел связи с параметрами гемодинамики и теста 6-минутной ходьбы, уровнем N-концевого мозгового натрийуретического пептида или ИМТ, но имел отрицательную ассоциацию с 3-летней выживаемостью: отношение рисков 0,18 ммоль/л (95% ДИ 0,07-0,47, p<0,01) [60].…”

Section: нарушение липидного обменаunclassified

“…Кроме низкого уровня ХС ЛПНП у пациентов с ЛАГ был отмечен низкий уровень общего холестерина и триглицеридов по сравнению с контрольной группой: −17,70 мг/дл (95% ДИ −24,15-11,26, p<0,00001) и −32,56 мг/дл (95% ДИ −54,17-−10,94, p=0,004), соответственно. В то же время данный метаанализ не выявил статистически значимой связи уровня ХС ЛПВП с наличием ЛАГ [59].…”

Section: нарушение липидного обменаunclassified

See 2 more Smart Citations

Pulmonary hypertension and metabolic disorders

Schelkova,

Yarovoy,

Dinevich

et al. 2024

jour

View full text Add to dashboard Cite

This review presents current data regarding the relationship between hyperuricemia, obesity, diabetes mellitus, lipid disorders and pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH). Hyperuricemia is associated with a higher risk of developing of PAH, worse prognosis of PAH and greater severity of the patient's condition. Obesity leads to the development of pro-inflammatory and vasoconstrictor effects, hypoxia, which contributes to the progression of PH, however, the survival rate of patients with PH and overweight or obesity is higher than with normal or reduced body weight. Diabetes mellitus and concomitant insulin resistance are associated with a high risk of hospitalization for right ventricular heart failure and mortality. The presence of PAH is associated with lower values of total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, and probably high-density lipoprotein cholesterol (HDL-C). At the same time, higher levels of LDL-С and HDL-С in PAH and CTEPH determine a better prognosis of the disease.All metabolic disorders considered have common mechanisms of influence on PH. Further study of their pathogenetic basis will make it possible to develop unified approaches to methods of their correction in patients with various types of pulmonary hypertension.

show abstract

Section: нарушение липидного обменаunclassified

See 1 more Smart Citation

Pulmonary hypertension and metabolic disorders

Schelkova,

Yarovoy,

Dinevich

et al. 2024

jour

View full text Add to dashboard Cite

show abstract

“…Noninvasive biomarkers are a promising diagnostic option, given their easy access and potential for risk stratification, targeted disease treatment, and monitoring response to therapy. 4 , 5 …”

Section: Introductionmentioning

confidence: 99%

RASA3 is a candidate gene in sickle cell disease‐associated pulmonary hypertension and pulmonary arterial hypertension

et al. 2023

View full text Add to dashboard Cite

Pulmonary hypertension (PH) is associated with significant morbidity and mortality. RASA3 is a GTPase activating protein integral to angiogenesis and endothelial barrier function. In this study, we explore the association of RASA3 genetic variation with PH risk in patients with sickle cell disease (SCD)‐associated PH and pulmonary arterial hypertension (PAH). Cis ‐expression quantitative trait loci (eQTL) were queried for RASA3 using whole genome genotype arrays and gene expression profiles derived from peripheral blood mononuclear cells (PBMC) of three SCD cohorts. Genome‐wide single nucleotide polymorphisms (SNPs) near or in the RASA3 gene that may associate with lung RASA3 expression were identified, reduced to 9 tagging SNPs for RASA3 and associated with markers of PH. Associations between the top RASA3 SNP and PAH severity were corroborated using data from the PAH Biobank and analyzed based on European or African ancestry (EA, AA). We found that PBMC RASA3 expression was lower in patients with SCD‐associated PH as defined by echocardiography and right heart catheterization and was associated with higher mortality. One eQTL for RASA3 (rs9525228) was identified, with the risk allele correlating with PH risk, higher tricuspid regurgitant jet velocity and higher pulmonary vascular resistance in patients with SCD‐associated PH. rs9525228 associated with markers of precapillary PH and decreased survival in individuals of EA but not AA. In conclusion, RASA3 is a novel candidate gene in SCD‐associated PH and PAH, with RASA3 expression appearing to be protective. Further studies are ongoing to delineate the role of RASA3 in PH.

show abstract

“…The gold standard approach to confirm PAH is right heart catheterization, but this is an invasive test that is not easily accepted by patients, so the development of biomarkers is an ongoing quest to improve outcomes. Researchers determined that none of the blood biomarkers identified in149 articles provide enough accuracy to replace current diagnostic approaches, either due to a lack of data or a lack of specificity [ 3 ]. To move closer towards precision medicine for PAH, there is an urgent need to identify novel biomarkers with high value.…”

Section: Introductionmentioning

confidence: 99%

Identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension

et al. 2023

View full text Add to dashboard Cite

Background The pathogenesis of pulmonary arterial hypertension (PAH) and associated biomarkers remain to be studied. Copper metabolism is an emerging metabolic research direction in many diseases, but its role in PAH is still unclear. Methods PAH-related datasets were downloaded from the Gene Expression Omnibus database, and 2067 copper metabolism-related genes (CMGs) were obtained from the GeneCards database. Differential expression analysis and the Venn algorithm were used to acquire the differentially expressed CMGs (DE-CMGs). DE-CMGs were then used for the coexpression network construction to screen candidate key genes associated with PAH. Furthermore, the predictive performance of the model was verified by receiver operating characteristic (ROC) analysis, and genes with area under the curve (AUC) values greater than 0.8 were selected as diagnostic genes. Then support vector machine, least absolute shrinkage and selection operator regression, and Venn diagrams were applied to detect biomarkers. Moreover, gene set enrichment analysis was performed to explore the function of the biomarkers, and immune-related analyses were utilized to study the infiltration of immune cells. The drug-gene interaction database was used to predict potential therapeutic drugs for PAH using the biomarkers. Biomarkers expression in clinical samples was verified by real-time quantitative PCR. Results Four biomarkers (DDIT3, NFKBIA, OSM, and PTGER4) were screened. The ROC analysis showed that the 4 biomarkers performed well (AUCs > 0.7). The high expression groups for the 4 biomarkers were enriched in protein activity-related pathways including protein export, spliceosome and proteasome. Furthermore, 8 immune cell types were significantly different between the two groups, including naive B cells, memory B cells, and resting memory CD4 T cells. Afterward, a gene-drug network was constructed. This network illustrated that STREPTOZOCIN, IBUPROFEN, and CELECOXIB were shared by the PTGER4 and DDIT3. Finally, the results of RT-qPCR in clinical samples further confirmed the results of the public database for the expression of NFKBIA and OSM. Conclusion In conclusion, four biomarkers (DDIT3, NFKBIA, OSM, and PTGER4) with considerable diagnostic values were identified, and a gene-drug network was further constructed. The results of this study may have significant implications for the development of new diagnostic biomarkers and actionable targets to expand treatment options for PAH patients.

show abstract

A systematic review with meta-analysis of biomarkers for detection of pulmonary arterial hypertension

Cited by 12 publications

References 93 publications

Pulmonary hypertension and metabolic disorders

Pulmonary hypertension and metabolic disorders

RASA3 is a candidate gene in sickle cell disease‐associated pulmonary hypertension and pulmonary arterial hypertension

Identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension

Contact Info

Product

Resources

About