European journal of pharmacology最新文献

{"title":"Modified lipoprotein-induced sFlt1 production in human placental trophoblasts is mediated by protein kinase C.","authors":"Rebecca P Chow, Jiawu Zhao, Yanchun Li, Tim M Curtis, Timothy J Lyons, Jeremy Y Yu","doi":"10.1016/j.ejphar.2024.177138","DOIUrl":"10.1016/j.ejphar.2024.177138","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is prevalent in women with diabetes, but the mechanism is unclear. We previously found that oxidized, glycated lipoproteins robustly upregulated soluble fms-like tyrosine kinase-1 (sFlt1), a key mediator of preeclampsia. Here, we determined the role of protein kinase C (PKC) and its subtypes in sFlt1 regulation in placental trophoblasts, and whether this mechanism might mediate the effect of modified lipoproteins.</p><p><strong>Methods: </strong>Cultured human HTR8/SVneo and BeWo trophoblasts were treated with the PKC activator phorbol-12-myristate-13-acetate (PMA) for 24h, ± PKC inhibitors GF109203X (general), Ro31-8220 (PKCα-selective), LY333531 (PKCβ-selective) and rottlerin (PKCδ-selective). The effect of 'heavily oxidized, glycated' low-density lipoproteins (HOG-LDL) vs. native LDL (N-LDL), ± high glucose (30 mM), was evaluated in HTR8/SVneo cells. sFlt1 secretion (ELISA), mRNA expression (RT-qPCR), and cellular PKC activity were measured.</p><p><strong>Results: </strong>PMA stimulated robust sFlt1 release and mRNA expression in both cell lines; these effects were inhibited by GF109203X, Ro31-8220 and LY333531 in a concentration-dependent manner. Rottlerin inhibited sFlt1 in BeWo, but modestly enhanced it in HTR8/SVneo cells. HOG-LDL enhanced PKC activity vs. N-LDL in HTR8/SVneo cells. Also, HOG-LDL, but not high glucose, significantly increased sFlt1 secretion and mRNA expression; this response was inhibited by GF109203X, Ro31-8220 and LY333531 at concentrations comparable to those that blocked PMA induction of sFlt1.</p><p><strong>Conclusion: </strong>Modified lipoproteins upregulate sFlt1 in trophoblasts via a PKC-mediated mechanism, involving at least α and β isoforms. The data suggest potential therapeutic targets to reduce the risk of preeclampsia in women with diabetes.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177138"},"PeriodicalIF":4.2,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of long non-coding RNAs for motor function recovery after spinal cord injury in rodents: A systematic review and meta-analysis.","authors":"Wenya Shang, Jing Huang, Yike Yang, Jia Guo, Huiyao Liu, Yafeng Ren","doi":"10.1016/j.ejphar.2024.177139","DOIUrl":"10.1016/j.ejphar.2024.177139","url":null,"abstract":"<p><strong>Objective: </strong>Long non-coding RNAs (LncRNAs) have garnered significant attention in preclinical studies for their potential in treating spinal cord injury (SCI). This meta-analysis aimed to assess the overall efficacy of lncRNA treatments in improving motor function in rodent models of SCI.</p><p><strong>Methods: </strong>The Embase, PubMed, Web of Science, and Scopus databases were searched. Meta-analysis was performed using STATA 14.0. The standardized mean difference (SMD) was employed to combine various motor function scores.</p><p><strong>Results: </strong>A total of 33 studies were included in this review. Key findings indicated that lncRNA treatments could markedly enhance locomotor function in rodents with SCI compared to control groups (SMD = 4.20, 95% CI: 3.35 to 5.05, I² = 80.0%, P < 0.0001). Furthermore, in male rats with contusion/compression injuries, targeting specific cytosol-enriched lncRNAs to downregulate their expression may significantly improve motor function recovery. Specifically, intrathecal injection of non-viral vectors for lncRNA delivery proved to be the most effective method in this study.</p><p><strong>Conclusions: </strong>LncRNA treatments have demonstrated the potential to improve motor function in rodent models with SCI. However, the therapeutic efficacy may be overestimated. Future research should rigorously assess the clinical translational efficacy and safety of lncRNA treatments.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177139"},"PeriodicalIF":4.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-Molecule Inhibitors in WNT Signalling Pathway for Targeted Cancer Therapy: Interplay between WNT, Autophagy and Apoptosis.","authors":"Nayana A Menon, Chethana D Kumar, Pournami Ramachandran, Britny Blaize, Mridul Gautam, Marco Cordani, Lekha Dinesh Kumar","doi":"10.1016/j.ejphar.2024.177137","DOIUrl":"https://doi.org/10.1016/j.ejphar.2024.177137","url":null,"abstract":"<p><p>Cancer represents an intricate and heterogeneous ailment that evolves from a multitude of epigenetic and genetic variations that disrupt normal cellular function. The WNT/β-catenin pathway is an essential one in maintaining the balance between cell renewal and differentiation in various tissues. Abnormal activation of this pathway can lead to uncontrolled cell growth and initiate cancer across a variety of tissues such as the colon, skin, liver, and ovary. It enhances characteristics that lead to cancer progression, including angiogenesis, invasion and metastasis. Processes like autophagy and apoptosis which regulate cell death and play a crucial role in maintaining cellular equilibrium are also intimately linked with WNT- β-catenin pathway. Thus, targeting WNT pathway has become a key strategy in developing antitumor therapies. Employing s has emerged as a targeted therapies to improve the clinical outcome compared to conventional cancer treatments. Many strategies for using small molecule inhibitors for modulating the WNT/β-catenin pathway, such as hindering WNT ligands' secretion or interaction, disrupting receptor complex, and blocking the nuclear translocation of β-catenin have been investigated. These interventions have shown promise in both preclinical and clinical settings. This review provides a comprehensive understanding of the role of WNT/β-catenin signalling pathway's role in cancer, emphasizing its regulation of autophagy and apoptosis. Our goal is to highlight the potential of specific small molecule inhibitors targeting this pathway, fostering the development of novel, tailored cancer treatments.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177137"},"PeriodicalIF":4.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin Attenuates Renal Tubular Ferroptosis in Preeclampsia via Tazarotene-Induced Gene 1.","authors":"Jiahao Tong, Lin Yang, Yuan Liu, Ying Yu, Lihong Zhang, Zengzhen Zhang, Zhenhao Yang, Qiaojing Qin, Jianying Niu, Yong Gu","doi":"10.1016/j.ejphar.2024.177140","DOIUrl":"https://doi.org/10.1016/j.ejphar.2024.177140","url":null,"abstract":"<p><p>Preeclampsia (PE) is a serious pregnancy complication characterized by elevated blood pressure and a major cause of maternal and perinatal morbidities, also known to increase the risk of chronic kidney disease. Mechanisms underlying PE-induced kidney injury remain unclear. Anti-angiotensin II type 1 receptor agonistic autoantibody (AT1-AA) is reported to participate in the pathogenesis of PE-induced kidney injury. Our previous study replicated the major features of PE in pregnant mice by administration of intravenous injection of AT1-AA and found that podocyte senescence plays a role in PE-induced kidney injury. Elevated levels of N-acetyl-β-D glucosaminidase (NAG) and kidney injury molecule-1 (KIM-1) in the urine of patients with PE have been reported, indicating renal tubular injury. In this study, we identified the role of renal proximal tubular epithelial cells (PTECs) in PE-induced kidney injury and the therapeutic value of empagliflozin, an anti-diabetic agent, in a murine model of AT1-AA-induced PE. In our study, higher tubular injury score (Control vs. PE: P<0.0001) show that PTECs are damaged in AT1-AA-induced PE. We identified ferroptosis as one of the cause of AT1-AA-induced PTEC injury by RNAseq, and confirmed the involvement of ferroptosis by detecting ferrous iron (Control vs. PE: P<0.0001), reduced glutathione (GSH) (Control vs. PE: P<0.0001) and lipid peroxidation (Control vs. PE: P<0.0001). Empagliflozin ameliorates AT1-AA-induced PTEC ferroptosis and injury in PE. Furthermore, we demonstrated that tazarotene-induced gene 1 is involved in AT1-AA-induced PTEC injury. These findings suggest that renal tubules are injured in PE and empagliflozin has therapeutic potential for PE-induced PTEC injury.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177140"},"PeriodicalIF":4.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Therapeutic Potential of Osmundacetone for Rheumatoid Arthritis: Effects and Mechanisms on Osteoclastogenesis.","authors":"Zirou Wang, Yan Liu, Chong Feng, Tianqi Li, Hongbao Xu, Yufan Ding, Weili Liu, Lingling Pu, Ran Li, Chongyi Ai, Zhaoli Chen, Xinxing Wang","doi":"10.1016/j.ejphar.2024.177135","DOIUrl":"https://doi.org/10.1016/j.ejphar.2024.177135","url":null,"abstract":"<p><p>The present study aimed to investigate the therapeutic potential of Osmundacetone (Osu), a natural plant product, for the treatment of rheumatoid arthritis (RA). The study revealed that Osu effectively reduced arthritis-induced swelling and bone destruction, as well as alleviating inflammation-related factors and oxidative stress in animal models. We focused the mechanism exploration on its regulatory mechanism on osteoclastogenesis in the next investigation. In vitro experiments demonstrated a dose-dependent inhibition of osteoclastic differentiation by Osu, as evidenced by tartrate resistant acid phosphatase (TRAP) staining and a reduction in osteoclastic differentiation markers observed through Western blotting analysis. And three different approaches Osu inhibiting osteoclastogenesis were found in our researches: (1) The binding of Receptor Activator of Nuclear Factor Kappa B (RANK) and Osu was revealed by the in-silico analysis. (2) According to 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining, Osu attenuated the level of reactive oxygen species (ROS), and western blotting studies revealed this effect was modulated by the regulation of Kelch-like ECH-associated protein 1 / Nuclear Factor erythroid 2-Related Factor 2 (Keap1/Nrf2) pathway. (3) Interestingly, we found that Osu increased the lipid peroxidation via downregulating the expression of glutathione peroxidase 4 (GPX4) at the same time as reducing the ROS, leading to the reduction of the fluidity of the membrane and the fusion of osteoclasts which could be reversed by using the ferroptosis inhibitor- Ferrostatin-1 (Fer-1). Overall, a natural compound to the existing therapeutics for rheumatoid arthritis was confirmed and a new strategy for inhibiting osteoclastogenesis was added.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177135"},"PeriodicalIF":4.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of how melatonin-upregulated clock genes PER2 and CRY2 alleviate rheumatoid arthritis-associated interstitial lung disease.","authors":"Yinping Huo, Yajie Gao, Bingle Li, Peiyao Zhang, Huiyang Liu, Guan Wang, Chunyan Pang, Yongfu Wang, Li Bai","doi":"10.1016/j.ejphar.2024.177136","DOIUrl":"https://doi.org/10.1016/j.ejphar.2024.177136","url":null,"abstract":"<p><p>Melatonin (Mel) serves as the central regulator for maintaining circadian rhythms and plays a crucial role not only in controlling the rhythmic clock, but also in several functional domains such as immunomodulation and anti-inflammation. In this study, we explored the clinical relevance of Mel and rheumatoid arthritis comorbid with interstitial lung disease (RA-ILD), and its potential therapeutic effects on arthropathy and pulmonary fibrosis (PF) in mice with collagen-induced arthritis (CIA). The results demonstrated that low serum levels of Mel were correlated with disease activity and severity of PF in RA-ILD patients. In addition, Mel was potentially efficacious in alleviating arthritis, bone destruction, and PF in a mouse model of CIA. Meanwhile, we observed that in lung tissues, the circadian-clock genes (CCGs) period circadian regulator 2 (PER2) and cryptochrome circadian regulator 2 (CRY2) were predominantly expressed in epithelial cells (ECs), and the regulation of their expression in ECs was closely correlated with Mel-mediated suppression of inflammatory responses and a significant reduction in macrophagic inflammatory activity. These results implied that Mel and its associated CCGs might play important regulatory roles in RA-ILD and its associated pathological processes.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177136"},"PeriodicalIF":4.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alanine mutation of the targeting subunit of the myosin phosphatase, MYPT1 at threonine 696 reduces cGMP responsiveness of mouse femoral arteries.","authors":"Lubomir T Lubomirov, Greta Weber, Mechthild Schroeter, Doris Metzler, Maria Bust, Tatyana Korotkova, Jürgen Hescheler, Vladimir T Todorov, Gabriele Pfitzer, Olaf Grisk","doi":"10.1016/j.ejphar.2024.177133","DOIUrl":"https://doi.org/10.1016/j.ejphar.2024.177133","url":null,"abstract":"<p><p>The femoral artery (FA) is the largest vessel in the hindlimb circulation and its proper tone regulation ensures adequate blood supply to muscle tissue. We investigated whether an alanine mutation of the targeting subunit of myosin-light-chain-phosphatase (MLCP), MYPT1, at threonine 696 (MYPT1-T696A/+), decisive for enzyme acivity, affects the responsiveness of young and old FAs (y-FAs and o-FAs) to activation of nitric-oxide/soluble-guanylate-cyclase/protein-kinase-G cascade (NO/sGC/PKG). Contractile responses of the vessels were measured by wire myography. Phosphorylation of the regulatory myosin-light-chain at serine 19 (MLC₂₀-S19), the myosin-light-chain-phosphatase targeting subunit, MYPT1-T696, the PKG-sensitive site of MYPT1 at S695 (MYPT1-S695) and S668 (MYPT1-S668), and the regulatory phosphorylation of eNOS at S1177 (eNOS-S1177) were determined in arterial homogenates by Western blot. In FAs of all ages, the MYPT1-T696A-mutation did not alter vessel diameter and the contractile reactivity to the thromboxaneA₂-analogue, U46619 and the RhoA kinase inhibitor, Y27632. In contrast, the mutation T696 into alanine attenuated the relaxing effect of exogenous NO (DEA-NONOate) in y-FAs. The effect of a direct sGC activation by cinaciguat was also attenuated in both age groups of MYPT1-T696A/+, but strongly in o-FA . The MYPT1-T696A-mutation also attenuated acetylcholine-induced relaxation, but only in o-FAs. Similary, the alanine mutation attenuated the acetylcholine effect on MLC₂₀-S19- and MYPT1-T696 only in WT o-FAs. Interestingly, neither eNOS-S1177 nor the phosphorylation of the PKG phosphospecific sites, MYPT1-S695 and MYPT1-S668 were altered by MYPT1-T696A-mutation or aging. These findings suggest that the alanine mutation of MYPT1-T696 reduces the ability of the NO/cGMP/PKG-system to relax FAs in aging.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177133"},"PeriodicalIF":4.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MitoQ enhances CYP19A1 expression to stimulate WNT/β-catenin signaling pathway for promoting hair growth in androgenetic alopecia","authors":"Yujie Li ,&nbsp;Tingru Dong ,&nbsp;Fenglan Yang ,&nbsp;Shiyu Jin ,&nbsp;Renxue Xiong ,&nbsp;Xiuzu Song ,&nbsp;Cuiping Guan","doi":"10.1016/j.ejphar.2024.177094","DOIUrl":"10.1016/j.ejphar.2024.177094","url":null,"abstract":"<div><div>Increased sensitivity to androgens and androgen receptors is the underlying cause of androgenetic alopecia (AGA), a hereditary disease. Our study investigated the preventive effects of MitoQ on dihydrotestosterone (DHT)-induced mitochondrial dysfunction and subsequent hair loss from three perspectives: <em>in vivo</em>, <em>in vitro</em>, and network pharmacology. A mouse model of AGA was used to assess the effectiveness of MitoQ intervention. Seventy-five drug targets and 367 disease targets were identified through network pharmacology analysis. Molecular docking analysis revealed that the androgen receptor (AR) and CYP19A1, which are key targets of MitoQ, may play a role in AGA treatment. CYP19A1 expression was downregulated in lesions from patients with AGA compared to healthy scalp tissue, while AR expression was upregulated. Cellular tests of human dermal papilla cells (DPCs) treated with MitoQ revealed that the mRNA and protein expression of AR remained unchanged, but the mRNA expression of CYP19A1 was upregulated. Our experiments also confirmed that CYP19A1 overexpression prevented DHT-induced apoptosis and upregulated the expression levels of WNT3A and β-catenin, whereas increased apoptosis levels and the downregulation of WNT3A and β-catenin due to CYP19A1 knockdown were reduced by MitoQ. We verified that MitoQ enhanced hair growth in DHT-induced hair loss model mice and reversed DHT-induced apoptosis by enhancing the expression of CYP19A1 in DPCs and that MitoQ may act by mediating the WNT/β-catenin pathway. These findings indicate that MitoQ could be a promising intervention for AGA and that CYP19A1 may serve as a valuable therapeutic target for AGA.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177094"},"PeriodicalIF":4.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological activation of aldehyde dehydrogenase 2 inhibits ferroptosis via SLC7A11/GPX4 axis to reduce kidney stone formation.","authors":"Jingdong Zhang, Rui Wang, Linguo Xie, Haotian Ren, Di Luo, Yu Yang, Haijie Xie, Zhiqun Shang, Chunyu Liu","doi":"10.1016/j.ejphar.2024.177132","DOIUrl":"10.1016/j.ejphar.2024.177132","url":null,"abstract":"<p><p>Calcium oxalate (CaOx) kidney stones pose a global health challenge due to their high prevalence and recurrence rates. While cell death mechanisms such as ferroptosis are known to play a crucial role in stone formation, the precise underlying mechanisms remain enigmatic. Aldehyde dehydrogenase 2 (ALDH2) is a metabolic enzyme of the ferroptosis product 4-hydroxy-2-nonenal (4-HNE). However, the function of ALDH2 in kidney stones is poorly understood. In this study, we observed a downregulation of ALDH2 in the stone group. Significantly, the administration of Alda-1, an ALDH2 agonist, notably reduced crystal deposition in the kidneys and hindered crystal adhesion to cells. Furthermore, Alda-1 induced upregulation of SLC7A11 expression, promoting glutathione synthesis, reducing lipid peroxidation accumulation, and lowering Fe²⁺ levels. These collective effects attenuated crystal-induced ferroptosis. However, the renoprotective effects of Alda-1 were inhibited by SLC7A11 siRNA. In conclusion, our study explores the applications of Alda-1 and highlights the potential of targeting ALDH2 as a promising therapeutical strategy for urolithiasis.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177132"},"PeriodicalIF":4.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative hypertension treatments: Transitioning from conventional therapies to siRNA-based solutions.","authors":"Reza Parvan, Joseph Pierre Aboumsallem, Wouter C Meijers, Rudolf A De Boer, A H Jan Danser","doi":"10.1016/j.ejphar.2024.177110","DOIUrl":"10.1016/j.ejphar.2024.177110","url":null,"abstract":"<p><p>Hypertension remains a critical global health issue, despite significant advancements in treatment, management and preventive approaches. Current antihypertensive drugs have limitations, such as low adherence, renin-angiotensin-aldosterone system reactivation, and drug resistance,. Ongoing preclinical and clinical studies for siRNA therapies show promising results, demonstrating significant blood pressure reductions and their potential as effective, durable treatments. This narrative review explores the potential of siRNA therapies in transforming hypertension management covering the literature until May 2024 and offering a precision medicine approach. We searched various databases, including PubMed, http://www.clinicaltrial.gov, and www.Espacenet.com, using 'hypertension' and 'siRNA' as the main keywords to retrieve relevant studies. The impact of these therapies could be profound, offering improved efficacy, reduced side effects, and enhanced patient adherence. As research continues to validate their safety and effectiveness, siRNA therapies may become integral components of hypertension management.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177110"},"PeriodicalIF":4.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}