Pharmacological research最新文献

{"title":"Agrin at the crossroads of aging: A pleiotropic regulator in age-related diseases","authors":"Jiayu Yuan ,&nbsp;Shun Zhang ,&nbsp;Dong Han ,&nbsp;Xiaoyu Dong","doi":"10.1016/j.phrs.2026.108131","DOIUrl":"10.1016/j.phrs.2026.108131","url":null,"abstract":"<div><div>Aging is a significant risk factor for numerous age-related diseases, and elucidating its key molecular mechanisms is crucial for disease prevention and treatment. Agrin, initially identified for its role in neuromuscular junction development, is an extracellular matrix protein. Recent studies have revealed its broad functions in maintaining tissue homeostasis and facilitating cellular signal transduction. During aging, alterations in the expression and function of Agrin may participate in the regulation of tissue repair, inflammatory responses, and intercellular communication, thereby influencing the onset and progression of various age-related diseases. This review systematically examines the central role of Agrin in age-related diseases such as Alzheimer’s disease, ischemic stroke, myocardial infarction, osteoarthritis, and type 2 diabetes. Accumulating evidence indicates that Agrin exhibits a distinct ‘‘double-edged sword’’ characteristic across different disease stages or tissue contexts—exerting protective effects in some scenarios while promoting pathological progression in others. We summarize current findings on the involvement of Agrin in disease mechanisms, including the regulation of amyloid deposition, blood-brain barrier integrity, synaptic function, inflammatory responses, and tissue repair. Furthermore, we discuss potential Agrin-targeted therapeutic strategies. We propose that Agrin represents a critical molecular node linking aging mechanisms with multiple age-related diseases. A deeper understanding of its context-dependent functional switching and the development of precise targeting approaches hold substantial promise for the prevention and treatment of age-related pathologies.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"225 ","pages":"Article 108131"},"PeriodicalIF":10.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Rationale of Seladelpar’s Clinical Efficacy through the Selective PPAR-δ Activation in Primary Biliary Cholangitis","authors":"Alessio Gerussi ,&nbsp;Matteo Fornai","doi":"10.1016/j.phrs.2026.108144","DOIUrl":"10.1016/j.phrs.2026.108144","url":null,"abstract":"<div><div>Seladelpar is a selective PPAR-δ agonist approved for the treatment of the rare cholestatic disease Primary Biliary Cholangitis, in patients who do not achieve adequate biochemical control with first-line therapy. This review outlines the characteristics of PPAR-δ, with insights into its activity across different tissues, and summarizes the pharmacology of Seladelpar, providing the background for the subsequent discussion of its clinical efficacy and safety in humans.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"225 ","pages":"Article 108144"},"PeriodicalIF":10.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on “Plasma miR-150-5p as a biomarker for immunosuppressive therapy response in acetylcholine receptor positive myasthenia gravis: A long-term prospective longitudinal study”","authors":"Shanshan Ru,&nbsp;Yingzhe Zhang","doi":"10.1016/j.phrs.2026.108117","DOIUrl":"10.1016/j.phrs.2026.108117","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"225 ","pages":"Article 108117"},"PeriodicalIF":10.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting FoxO1 in cardiovascular diseases: Mechanisms and therapeutic potential","authors":"Xue Wu ,&nbsp;Xia Du ,&nbsp;Chenxi Lu","doi":"10.1016/j.phrs.2026.108122","DOIUrl":"10.1016/j.phrs.2026.108122","url":null,"abstract":"<div><div>Cardiovascular Disease (CVDs), as a major life-threatening disease, has attracted worldwide attention. Seeking novel and effective therapeutic strategies is still among the important in the cardiovascular field. Forkhead box O (FoxO) family comprises a group of transcription factors with highly conserved structures that have a major role in a plethora of biological functions. Recently, a considerable amount of research has shown the physiological and pathological roles of Fox family (especially FoxO1) in CVDs (including myocardial ischemia-reperfusion injury, myocardial hypertrophy, myocardial infarction, myocardial fibrosis, cardiomyopathy, and atherosclerosis), and they affect the plasticity, stress response, and metabolism of the heart by regulating various signaling pathways and biological functions. In this review, we outline the structure of the Fox family and FoxO1. Next, we summarize the various pathological and physiological mechanisms of FoxO1 (inflammation, oxidative stress, autophagy, endothelial dysfunction, lipid metabolism and angiogenesis), as well as the regulatory style of FoxO1 (phosphorylation, methylation, ubiquitination and acetylation). Finally, we also reviewe the latest research advancements and potential future research directions concerning FoxO1 regulators in CVDs, laying the foundation for its transformation into a new and powerful clinical application.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"225 ","pages":"Article 108122"},"PeriodicalIF":10.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A resveratrol–hydrogen sulfide donor hybrid as a multi-target therapeutic strategy for allergic asthma","authors":"Martina Simonelli ,&nbsp;Ida Cerqua ,&nbsp;Danilo D’Avino ,&nbsp;Elisabetta Granato ,&nbsp;Alessandra Perrella ,&nbsp;Sara Perna ,&nbsp;Antonietta Rossi ,&nbsp;Raffaele Capasso ,&nbsp;Federica Sodano ,&nbsp;Antonia Scognamiglio ,&nbsp;Elisa Magli ,&nbsp;Ferdinando Fiorino ,&nbsp;Giuseppe Caliendo ,&nbsp;Beatrice Severino ,&nbsp;Angela Corvino ,&nbsp;Fiorentina Roviezzo","doi":"10.1016/j.phrs.2026.108121","DOIUrl":"10.1016/j.phrs.2026.108121","url":null,"abstract":"<div><div>Resveratrol (RESV) is a naturally occurring polyphenol with well-established antioxidant and anti-inflammatory properties, supporting its therapeutic potential in chronic respiratory diseases such as asthma. To enhance its efficacy, we developed a hybrid compound, R-TBZ, in which RESV is chemically linked to 4-hydroxythiobenzamide (TBZ), a slow-releasing hydrogen sulfide (H₂S) donor. This design aimed to improve chemical stability, bioavailability, and controlled activation while minimizing the toxicity associated with fast H₂S release. R-TBZ was synthesized via esterification of RESV with TBZ and showed high chemical stability, remaining over 95 % intact after 24 h under neutral and acidic conditions. Enzymatic hydrolysis occurred gradually (t₁/₂ ≈ 20 h), releasing RESV as the sole detectable product. In allergen-challenged bronchial epithelial cells, R-TBZ demonstrated superior efficacy compared with RESV or TBZ alone. It enhanced mitochondrial antioxidant defenses, reduced mucus production, and suppressed pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). R-TBZ inhibited allergen-induced epithelial–mesenchymal transition and TGF-β–induced fibroblast activation, reducing α-SMA and vimentin expression more effectively than the parent compounds, indicating synergistic anti-remodeling activity. In a murine model of allergic asthma, R-TBZ improved lung function, reduced airway hyperresponsiveness, restored β₂-agonist responsiveness, and attenuated eosinophilic inflammation, Th2 cytokine production, and plasma IgE levels. Importantly, R-TBZ reversed airway structural remodeling, reducing peribronchial α-SMA expression and preserving epithelial and goblet cell morphology, effects not fully achieved by RESV alone. Overall, R-TBZ combines dual anti-inflammatory and anti-remodeling activities, overcoming key limitations of RESV and H₂S donors. This hybrid represents a promising multi-target therapeutic strategy for asthma, particularly for steroid-resistant airway remodeling.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"225 ","pages":"Article 108121"},"PeriodicalIF":10.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Impaired PARP1-dependent DNA repair in MORC2 mutations drives axonal degeneration in Charcot-Marie-Tooth disease subtype 2Z and spinal muscular atrophy-like neuromotor disorders” [Pharmacol. Res. 224 (2026) 108103]","authors":"Mengli Wang ,&nbsp;Honglan Yang ,&nbsp;Zhongzheng Li ,&nbsp;Sen Zeng ,&nbsp;Ke Xu ,&nbsp;Binghao Wang ,&nbsp;Yongzhi Xie ,&nbsp;Qingping Wang ,&nbsp;Zhuolin Su ,&nbsp;Mingri Zhao ,&nbsp;Yiti Zhang ,&nbsp;Mujun Liu ,&nbsp;Beisha Tang ,&nbsp;Xionghao Liu ,&nbsp;Ruxu Zhang","doi":"10.1016/j.phrs.2026.108119","DOIUrl":"10.1016/j.phrs.2026.108119","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"225 ","pages":"Article 108119"},"PeriodicalIF":10.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-in-human evaluation of four novel PSMA-targeted PET radiotracers with non-canonical amino acid linkage: A comparative study","authors":"Dong Dai ,&nbsp;Xin Gao ,&nbsp;Siqi Zhang ,&nbsp;Hongyi Huang ,&nbsp;Kun Wang ,&nbsp;Jianjing Liu ,&nbsp;Xingkai Wang ,&nbsp;Yuan Miao ,&nbsp;Zongxiao Liu ,&nbsp;Panfeng Li ,&nbsp;Qingshuang Lu ,&nbsp;Shuo Jiang ,&nbsp;Xueyao Chen ,&nbsp;Licheng Yang ,&nbsp;Yiliang Li ,&nbsp;Rui Wang ,&nbsp;Yingzi Zhang ,&nbsp;Kuan Hu","doi":"10.1016/j.phrs.2026.108138","DOIUrl":"10.1016/j.phrs.2026.108138","url":null,"abstract":"<div><div>PSMA-targeted radiopharmaceuticals have substantially advanced the management of prostate cancer; however, high nonspecific uptake in organs such as salivary glands and kidneys remains a clinical challenge. In our previous studies, incorporation of non-canonical amino acid linkers was shown to reduce off-target uptake while preserving or even enhancing tumor accumulation of PSMA-targeted radiotracers. Here, we present a first-in-human head-to-head comparison in which each of four linker-optimized PSMA radiotracers—[⁶⁸Ga]Ga-PSMA-HK4, [⁶⁸Ga]Ga-PSMA-HK7, [⁶⁸Ga]Ga-PSMA-Y55, and [⁶⁸Ga]Ga-PSMA-Y81—was individually compared with either [⁶⁸Ga]Ga-PSMA-617 or [⁶⁸Ga]Ga-PSMA-11, evaluating their <em>in vivo</em> pharmacokinetics and diagnostic performance in eight prostate cancer patients. Preclinical data demonstrated that all four radiotracers achieved comparable or enhanced tumor uptake, with [⁶⁸Ga]Ga-PSMA-Y55 and [⁶⁸Ga]Ga-PSMA-Y81 showing reduced renal accumulation relative to [⁶⁸Ga]Ga-PSMA-617. Clinically, [⁶⁸Ga]Ga-PSMA-HK4 and [⁶⁸Ga]Ga-PSMA-HK7 exhibited lower salivary gland uptake, whereas [⁶⁸Ga]Ga-PSMA-Y55 and [⁶⁸Ga]Ga-PSMA-Y81 showed decreased renal retention compared with reference tracers. Tumor uptake of [⁶⁸Ga]Ga-PSMA-HK4 and [⁶⁸Ga]Ga-PSMA-Y55 was comparable to [⁶⁸Ga]Ga-PSMA-617, while [⁶⁸Ga]Ga-PSMA-HK7 and [⁶⁸Ga]Ga-PSMA-Y81 displayed prolonged blood pool and cardiac retention. These clinical findings indicate that β³-amino acid linkers effectively reduced salivary gland uptake, while linker stereochemistry modulated renal clearance of PSMA radiotracers. Even subtle atomic-level linker variations resulted in substantial preclinical and clinical pharmacokinetic divergence, highlighting the necessity of precise molecular engineering in PSMA radiopharmaceuticals to achieve an improved tumor therapeutic index while reducing nonspecific toxicity.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"225 ","pages":"Article 108138"},"PeriodicalIF":10.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic-derived extracellular vesicles attenuate cholestatic liver damage via gut-liver axis","authors":"Xianjiao Liu ,&nbsp;Yanyan Wang ,&nbsp;Andrea Abreo Medina ,&nbsp;Dandan Liu ,&nbsp;Jinyan Liu ,&nbsp;Wenxuan Tang ,&nbsp;Mengmeng Wang ,&nbsp;Xingxiang Chen ,&nbsp;Kehe Huang ,&nbsp;Min Liu ,&nbsp;Chunfeng Wang ,&nbsp;Yunhuan Liu","doi":"10.1016/j.phrs.2026.108152","DOIUrl":"10.1016/j.phrs.2026.108152","url":null,"abstract":"<div><div>Gut-liver axis disturbance is the unifying pathogenesis of cholestatic liver diseases. The purpose of this study was to explore the underlying mechanisms of the probiotic <em>Lactobacillus amylovorus</em> (LA) and its secreted extracellular vesicles (EVs) on liver damage and fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed and multidrug resistance protein 2 knockout (<em>Mdr2</em>^<em>-/-</em>) mice. Direct replenishment of LA is sufficient to correct the DDC-fed and <em>Mdr2</em>^<em>-/-</em>-induced liver damage and fibrosis. Mechanistic studies show that the secretion of EVs is required for the LA-induced liver protective effects. RNA sequencing results demonstrated that the enrichment of differentially expressed genes was associated with glutathione metabolism, microbial metabolism in diverse environments and inflammatory mediator regulation of TRP channels in DDC-fed mice. Our findings revealed that LAEVs reshaped the gut microbiota, which was associated with increased bile acids (BAs) deconjugation and fecal BAs excretion, repaired gut barrier function, activated intestinal Farnesoid X receptor/Fibroblast growth factor 15 (FXR/FGF-15) axis, reduced liver BAs and oxidative stress level, which ultimately mitigated liver damage and fibrosis in both DDC-fed and <em>Mdr2</em>^<em>-/-</em> mice. Notably, LAEVs did not ameliorate DDC-induced liver damage or fibrosis in antibiotic-treated mice. Furthermore, LAEVs provided protection against DDC-induced liver injury and fibrosis in fecal microbiota transplantation mice. LAEVs did not ameliorate DDC-induced liver damage or fibrosis in BSH inhibitor (CAPE)-treated mice. LAEVs also failed to improve liver damage and fibrosis in DDC-induced intestinal epithelial cell-specific FXR knockout (<em>Fxr</em>^{<em>△IE</em>}) mice. This study revealed that LAEVs mitigated cholestatic liver fibrosis via regulating gut microbiota-bile acid-ROS axis in mice.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"225 ","pages":"Article 108152"},"PeriodicalIF":10.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropilin-1 acts as a co-receptor of IL-13 to reprogram macrophages in liver fibrosis","authors":"Chenxi Liu ,&nbsp;Yingchun Wang ,&nbsp;Yinuo Yang ,&nbsp;Miaomiao Tian ,&nbsp;Tiantian Liu ,&nbsp;Songbo Zhao ,&nbsp;Le Wang ,&nbsp;Lifen Gao ,&nbsp;Yuemin Feng ,&nbsp;Jianni Qi ,&nbsp;Qiang Zhu","doi":"10.1016/j.phrs.2026.108112","DOIUrl":"10.1016/j.phrs.2026.108112","url":null,"abstract":"<div><div>Neuropilin-1 (NRP-1) is a pleiotropic transmembrane receptor critical in embryonic development of neurological and vascular systems. Increasing evidence suggests that NRP-1 has a major role in immunity. However, the role of NRP-1 in regulating the profibrotic function of macrophages during liver fibrosis has not been defined. In this study, we collected human liver samples from 20 patients with fibrosis and 5 controls, finding significantly elevated NRP-1 expression in macrophages from fibrotic livers. Using macrophage-specific NRP-1 deficient mice subjected to CCl₄-induced liver fibrosis, we demonstrated that NRP-1 deficiency effectively attenuated fibrotic progression. Further experiments revealed that NRP-1 enhances profibrotic macrophage polarization and subsequent hepatic stellate cell activation both in vivo and in vitro. Mechanistically, NRP-1 binds to interleukin-13 receptor alpha1 (IL13Rα1) via its extracellular domain, stabilizing the IL13Rα1-IL13 interaction. This activates IL13 signaling, leading to Tyk2 phosphorylation. The IL13Rα1-Tyk2/Stat6 axis then upregulates the transcription factor EHF, which in turn activates NRP-1 expression in macrophages, establishing a positive feedback loop that amplifies profibrotic functions. Our conclusions indicate that NRP-1 promotes liver fibrosis progression, and targeting macrophage NRP-1 is a potential therapeutic strategy against liver fibrosis.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"225 ","pages":"Article 108112"},"PeriodicalIF":10.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial versus global METRNL reveals importance of endothelial METRNL against atherosclerosis via mitochondrial homeostasis","authors":"Dao-Xin Wang ,&nbsp;Pin Wang ,&nbsp;Zhu-Wei Miao ,&nbsp;Shu-Na Wang ,&nbsp;Si-Li Zheng ,&nbsp;Xue-Lian Wang ,&nbsp;Jia-Xin Li ,&nbsp;Zhi-Yong Li ,&nbsp;Yu Chen ,&nbsp;Tian-Guang Zhang ,&nbsp;Chao-Yu Miao","doi":"10.1016/j.phrs.2026.108123","DOIUrl":"10.1016/j.phrs.2026.108123","url":null,"abstract":"<div><div>We recently showed that METRNL (Meteorin-like) protects against atherosclerosis. However, the mechanism for METRNL in atherosclerosis is largely unclear. This study aimed to demonstrate the relative importance of endothelial METRNL in atherosclerosis by comparing the effects of whole-body METRNL deficiency to endothelial-specific deficiency, and to show the subcellular distribution of endothelial METRNL and its role in mitochondrial homeostasis against atherosclerosis. Our study demonstrated that a deficiency in either endothelial or global METRNL exacerbated atherosclerosis to a similar degree in both spontaneous (age-related) and high fat diet-induced atherosclerosis, suggesting that endothelial METRNL is pivotal in the progression of atherosclerosis due to METRNL deficiency. Endothelial METRNL was diffusely distributed in the cytoplasm with subcellular localization to mitochondria, nucleus, endoplasmic reticulum, and Golgi apparatus (especially enriched in mitochondria and nucleus). In both an <em>in vivo apolipoprotein E</em>-deficient (<em>ApoE</em>^-/-) mouse model and an <em>in vitro</em> oxidized low density lipoprotein (ox-LDL)-treated endothelial cell model, METRNL inhibited ox-LDL- or high fat diet-induced atherosclerosis by alleviating endothelial mitochondrial dysfunction and apoptosis which was achieved through a balance between PPARγ co-activator-1α (PGC-1α)-mediated mitochondrial biogenesis and PTEN induced putative kinase protein 1 (PINK1)-Parkin-mediated mitophagy. These findings highlight the pivotal importance of endothelial METRNL against atherosclerosis by comparison with whole-body METRNL. This is the first demonstration of METRNL localization to mitochondria in endothelial cells and its role in maintaining endothelial mitochondrial stability against atherosclerosis. Furthermore, targeting METRNL to stabilize endothelial mitochondrial function represents a novel and promising therapeutic strategy for atherosclerotic cardiovascular diseases.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"225 ","pages":"Article 108123"},"PeriodicalIF":10.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}