PCSK9 inhibitor alleviates experimental pulmonary fibrosis-induced pulmonary hypertension via attenuating epithelial-mesenchymal transition by suppressing Wnt/β-catenin signaling in vivo and in vitro DOI Creative Commons
Jiancheng Lin,

Zetao Pan,

Jiayan Sun

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 11, 2024

Background The co-occurrence of pulmonary hypertension (PH) in patients with fibrosis (PF) is linked to a more unfavorable prognosis and increased mortality compared PF cases without PH. Early intervention comprehensive management are pivotal for improving survival outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein essential cholesterol metabolism. However, the potential PCSK9 inhibition alleviate PF-induced PH has not been previously reported. Methods A mouse model was established using intratracheal injection bleomycin (BLM), followed by administration inhibitor every other day. Data on right ventricle (RV) remodeling changes arteries were collected analyzed. Transforming growth factor-beta (TGF-β) also administered MLE-12 cells as an experimental lung model. mechanisms PCSK9’s impact examined both vivo vitro . Results Inhibition significantly reduced artery thickening RV BLM-induced Moreover, blockage effectively attenuated migration epithelial-mesenchymal transition (EMT) process TGF-β-induced cells. We observed that suppressed expression Wnt/β-catenin pathway animal cell experiments. Conclusion plays crucial role progression regulating EMT signaling. Targeting or activity could control its complication.

Language: Английский

Hypercholesterolemia and inflammation—Cooperative cardiovascular risk factors DOI Creative Commons

Antonio Gallo,

Wilfried Le Goff,

Raul D. Santos

et al.

European Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 6, 2024

Abstract Background Maintaining low concentrations of plasma low‐density lipoprotein cholesterol (LDLc) over time decreases the number LDL particles trapped within artery wall, slows progression atherosclerosis and delays age at which mature atherosclerotic plaques develop. This substantially reduces lifetime risk cardiovascular disease (ASCVD) events. In this context, plaque development vulnerability result not only from lipid accumulation but also inflammation. Results Changes in composition immune cells, including macrophages, dendritic T B mast cells neutrophils, along with altered cytokine chemokine release, disrupt equilibrium between inflammation anti‐inflammatory mechanisms sites. Considering that it is a competition LDLc inflammation, instead they are partners crime, present narrative review aims to give an overview main inflammatory molecular pathways linked raised describe impact lipid‐lowering approaches on burden. Although remarkable changes driven by most recent lowering combinations, relative reduction C‐reactive protein appears be independent magnitude lowering. Conclusion Identifying clinical biomarkers (e.g. interleukin‐6) possible targets for therapy holds promise monitoring reducing ASCVD burden suitable patients.

Language: Английский

Citations

7
PCSK9 in Vascular Aging and Age-Related Diseases DOI Creative Commons

Dong Tan,

Xin Yang, Jing Yang

et al.

Aging and Disease, Journal Year: 2025, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2025

Language: Английский

Citations

0
PCSK9 Inhibitors: Focus on Evolocumab and Its Impact on Atherosclerosis Progression DOI Creative Commons
Maram H. Abduljabbar

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1581 - 1581

Published: Nov. 25, 2024

This paper investigates the therapeutic use of PCSK9 inhibitors, particularly Evolocumab, as monoclonal antibodies for treatment atherosclerosis based on recent literature reviews. is an outstanding example a breakthrough in medical science, with advancements understanding its biological function driving substantial progress treatment. Atherosclerotic cardiovascular disease (ASCVD) leading global cause mortality, imposing financial burdens healthcare systems. Elevated low-density lipoprotein cholesterol (LDL-C), modifiable risk factor, plays pivotal role development ASCVD. Emerging treatments such inhibitors are now being introduced to combat this issue, goal reducing ASCVD by directly targeting LDL-C levels. discovery highlighted potential inhibit PCSK9, thereby enhancing receptor activity. led Alirocumab and Evolocumab which typically reduce levels approximately 50%. research underscores importance treating ASCVD, drawing evidence from various randomized controlled trials FOURIER, ODYSSEY OUTCOMES, VESALIUS-CV. These have also shown that effective safe several disorders. therefore useful patients who do not reach their target when highest doses statins or very high cannot tolerate at all.

Language: Английский

Citations

1
Comprehensive Assessment of PCSK9 Inhibitors for Lipid Management: Scientific Guidance Based on Drug Selection Recommendations for Chinese Medical Institutions DOI Creative Commons
Jiabao Li, Siyong Huang, Xiao Hu

et al.

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 6297 - 6312

Published: Dec. 1, 2024

This study aims to support the selection of PCSK9 inhibitors for patients requiring lipid management within medical institutions. By quantitatively evaluating four inhibitors, we provide evidence-based guidance optimal in this patient population.

Language: Английский

Citations

1
PCSK9 inhibitor alleviates experimental pulmonary fibrosis-induced pulmonary hypertension via attenuating epithelial-mesenchymal transition by suppressing Wnt/β-catenin signaling in vivo and in vitro DOI Creative Commons
Jiancheng Lin,

Zetao Pan,

Jiayan Sun

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 11, 2024

Background The co-occurrence of pulmonary hypertension (PH) in patients with fibrosis (PF) is linked to a more unfavorable prognosis and increased mortality compared PF cases without PH. Early intervention comprehensive management are pivotal for improving survival outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein essential cholesterol metabolism. However, the potential PCSK9 inhibition alleviate PF-induced PH has not been previously reported. Methods A mouse model was established using intratracheal injection bleomycin (BLM), followed by administration inhibitor every other day. Data on right ventricle (RV) remodeling changes arteries were collected analyzed. Transforming growth factor-beta (TGF-β) also administered MLE-12 cells as an experimental lung model. mechanisms PCSK9’s impact examined both vivo vitro . Results Inhibition significantly reduced artery thickening RV BLM-induced Moreover, blockage effectively attenuated migration epithelial-mesenchymal transition (EMT) process TGF-β-induced cells. We observed that suppressed expression Wnt/β-catenin pathway animal cell experiments. Conclusion plays crucial role progression regulating EMT signaling. Targeting or activity could control its complication.

Language: Английский

Citations

0