Basic Research in Cardiology最新文献

{"title":"Cardiomyocyte-derived IL-30 improves cardiac repair by reducing splenic germinal center activation after myocardial infarction.","authors":"Siqin Chen, Jinghong Zhang, Sirui Huang, HanChuan Chen, Jin Liu, Zhaokuan Li, Yifan Ding, Peiyuan Bai, Qixin Chen, Naifu Wan, Yanqiu Huang, Zhinan Yin, YanSong Guo, Aijun Sun, Daile Jia, Junbo Ge","doi":"10.1007/s00395-026-01214-4","DOIUrl":"https://doi.org/10.1007/s00395-026-01214-4","url":null,"abstract":"<p><p>Following myocardial infarction (MI), splenic humoral immune responses contribute to cardiac injury and repair, yet the cardiac signals that govern these responses remain poorly defined. Here, we identified ischemic cardiomyocytes as a source of interleukin 30 (IL-30; the interleukin 27 p28 subunit) and investigated its role in heart-spleen communication. In mice, cardiomyocyte-specific IL-30 deficiency enhanced splenic germinal center responses and signal transducer and activator of transcription 1 (STAT1) phosphorylation. This deficiency increased myocardial IgG deposition, TNF-α expression in Fc gamma receptor III-positive macrophages, and cardiomyocyte apoptosis, while impairing cardiac function and aggravating ventricular remodeling. Recombinant IL-30 suppressed splenic germinal center responses and STAT1 phosphorylation and improved cardiac function. The effects of recombinant IL-30 on germinal center responses and cardiac function were abolished by B cell-specific deletion of glycoprotein 130 (gp130). Furthermore, no detectable improvement in cardiac function was observed following IL-30 treatment in splenectomized mice. In patients with ST-segment elevation myocardial infarction (STEMI; n = 75), lower circulating IL-30 levels were associated with higher peripheral IgG-positive B cell frequencies. In a separate longitudinal cohort of 247 patients with STEMI, low circulating IL-30 was independently associated with adverse left ventricular remodeling at 6 months (odds ratio, 4.44; 95% confidence interval, 2.16-9.80; P< 0.001). Circulating IL-30 discriminated patients with and without adverse remodeling with an area under the receiver operating characteristic curve of 0.738. These findings identify cardiomyocyte-derived IL-30 as an endogenous regulator of heart-spleen communication that restrains splenic humoral responses and limits adverse cardiac remodeling after MI.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β signalling drives chemotaxis of human induced pluripotent stem cell-derived cardiomyocytes in response to MI stimulus.","authors":"Laura Deelen, Kazuya Kobayashi, Gowtham Reddy Cheruku, Alia Hafiz Abbas Gasim, Fiona Lewis-McDougall, Ken Suzuki","doi":"10.1007/s00395-026-01201-9","DOIUrl":"10.1007/s00395-026-01201-9","url":null,"abstract":"<p><p>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold significant promise for cardiac regeneration therapies. However, the efficacy of such treatments depends on the ability of transplanted cells to migrate and integrate into the damaged myocardium, a process that remains poorly understood. In this study, we investigated the migratory behaviour of hiPSC-CMs using homogenised rat MI tissue to simulate myocardial infarction (MI) in vitro. Transwell migration assays demonstrated a concentration-dependent chemotactic response, with hiPSC-CM migration increasing up to threefold towards MI tissue homogenate. Wound-healing assays further confirmed enhanced migration under MI-mimetic conditions. Bulk RNA sequencing revealed activation of the TGF-β signalling pathway as a key regulator of this response. Inhibition of TGF-β signalling, both pharmacologically and through antibody neutralisation, significantly reduced hiPSC-CM migration. These findings uncover a previously underappreciated chemotactic capability of hiPSC-CMs and identify TGF-β signalling as a central mediator, offering new mechanistic insights and potential therapeutic targets to improve the integration and efficacy of hiPSC-CM-based cardiac regeneration strategies.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"1063-1076"},"PeriodicalIF":9.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLRX1 emerges as the only observed essential regulator of the mPTP, challenging mPTP inhibition as a valid target of cardioprotection.","authors":"Kielen R Zuurbier, Coert J Zuurbier","doi":"10.1007/s00395-026-01204-6","DOIUrl":"10.1007/s00395-026-01204-6","url":null,"abstract":"<p><p>The mitochondrial permeability transition pore (mPTP) opening is a phenomenon in which the inner mitochondrial membrane abruptly becomes permeable when matrix calcium reaches a critical threshold. Despite 5 decades of intensive research, no protein has been universally accepted as essential for mPTP opening, limiting mechanistic understanding and raising questions about the validity of mPTP-targeted strategies to mitigate cardiac ischemia-reperfusion (I/R) injury. Here, we discuss convergent findings from two independent laboratories identifying the innate immune receptor NLRX1 as an unexpected, essential requirement for mPTP activity. NLRX1 is the only NOD-like receptor (NLR) that is targeted to the mitochondrion. NLRX1 deficiency abolishes (1) calcium-induced mPTP opening, (2) cyclosporine A sensitivity of the pore, and (3) mitochondrial calcium release following cardiac I/R. To test whether loss of mPTP function aligns with loss of NLRX1 across evolution, we performed forward and reciprocal bioinformatic (Blastp) searches and found that species reported to lack an mPTP (e.g., Artemia franciscana and Drosophila melanogaster) also lack NLRX1, further supporting a mandatory role for NLRX1 in mPTP occurrence. Notably, NLRX1-deficient hearts can exhibit increased, rather than decreased, I/R injury at specific ischemia durations. This mirrors reports that deletion of established mPTP regulators (e.g., Ppif) may also worsen injury under defined conditions, consistent with context-dependent, potentially protective roles for transient mPTP activity (e.g., mitochondrial calcium release, PI3K/Akt signaling). In summary, we propose that NLRX1 is the only currently identified protein that is strictly required for mPTP opening, and that indiscriminate inhibition of the mPTP is unlikely to represent a universally effective cardioprotective strategy against I/R injury.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"827-835"},"PeriodicalIF":9.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fast skeletal myosin binding protein-C expression exacerbates dysfunction in heart failure.","authors":"James W McNamara, Taejeong Song, Perwez Alam, Akhil Baby, Aleksandra Binek, Kalyani Ananthamohan, Rohit R Singh, Michelle L Nieman, Marloes van den Berg, Brent M Cernyar, Sheryl E Koch, Malina J Ivey, Thomas L Lynch, James T Pearson, Jack Rubinstein, J-P Jin, John N Lorenz, Jennifer E Van Eyk, Onur Kanisicak, Sakthivel Sadayappan","doi":"10.1007/s00395-026-01202-8","DOIUrl":"10.1007/s00395-026-01202-8","url":null,"abstract":"<p><p>During heart failure (HF), gene and protein expression profiles undergo extensive compensatory and pathological remodeling. We previously observed that fast skeletal myosin binding protein-C (fMyBP-C) is upregulated in diseased mouse hearts. While fMyBP-C shares significant homology with its cardiac paralog, cardiac myosin binding protein-C (cMyBP-C), there are key differences that may affect cardiac function. However, the consequence of cardiac expression of fMyBP-C is unknown. Here, we aim to elucidate the impact of fMyBP-C expression on cardiac function and pathology. To determine the sufficiency of fMyBP-C to cause cardiac dysfunction, we generated cardiac-specific fMyBP-C over-expression mice. These mice were crossed into cMyBP-C null mice to assess the effect of fMyBP-C in the complete absence of cMyBP-C. Finally, fMyBP-C null mice underwent transverse aortic constriction (TAC) to define the requirement of fMyBP-C in HF. We confirmed the upregulation of fMyBP-C in several models of cardiac disease, including lineage tracing models. Low levels of fMyBP-C caused mild cardiac remodeling and sarcomere dysfunction. Exclusive expression of fMyBP-C in a HF model exacerbated cardiac pathology. Furthermore, reduction of fMyBP-C expression by shRNA in HF improved cardiac function. Following pressure overload, fMyBP-C null mice demonstrated greater resistance to cardiac decompensation. Mechanistically, our data suggest the differential regulation of the myosin super-relaxed state by cMyBP-C and fMyBP-C plays a contributing role. These findings suggest the elevated expression of fMyBP-C in diseased hearts is a pathological response. Targeted therapies to prevent upregulation of fMyBP-C may prove beneficial in the treatment of HF.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"1047-1061"},"PeriodicalIF":9.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meteorin-like regulates cardiac repair via macrophage modulation following myocardial infarction.","authors":"G Ferrer-Curriu, A Blasco-Roset, A Navarro-Gascon, C Soler-Botija, F J Godoy-Nieto, M Monguió-Tortajada, R Cereijo, T Quesada-Lopez, F Rueda, S Roura, C Gálvez-Montón, F Villarroya, A Bayés-Genís, A Planavila","doi":"10.1007/s00395-026-01203-7","DOIUrl":"10.1007/s00395-026-01203-7","url":null,"abstract":"<p><p>After myocardial infarction (MI), the heart undergoes a reparative process that includes an initial acute inflammatory phase followed by a subsequent reparative phase. The transition between these phases is crucial for cardiac recovery, but the key factors remain unclear. Meteorin-like (Metrnl) promotes anti-inflammatory/reparative macrophage polarization in the myocardium, yet its role in the acute phase post-MI is unknown. We observed that macrophages infiltrating the ischemic myocardium produced elevated levels of Metrnl in both the heart and circulation 4 days post-MI. The absence of Metrnl in Metrnl⁻/⁻ mice altered myocardial healing and remodeling, with an increased presence of macrophages with a more pro-inflammatory phenotype. Conversely, cardiac Metrnl overexpression restored myocardial repair and promoted a shift toward a more anti-inflammatory/reparative macrophage phenotype. Mechanistically, Metrnl regulated macrophage-dependent production of Oncostatin M (Osm), a key cytokine in the early inflammatory phase post-MI that induces cardiomyocyte production of Reg3β. Reg3β, in turn, limits pro-inflammatory macrophage activation and polarization while modulating their trafficking, ultimately influencing the duration and intensity of the pro-inflammatory phase post-MI. Thus, Metrnl plays a crucial role in cardiac repair by modulating the acute phase following myocardial infarction through its regulation of macrophage populations.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"987-1010"},"PeriodicalIF":9.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P38α deficiency alleviates myocardial ischemia/reperfusion injury by stabilizing c‑Myc to inhibit ferroptosis.","authors":"Xiaohu Ouyang, Shuxin Song, Yalan Dong, Mi Xiang, Liangqingqing Yin, Xunxun Wang, Yan Ma, Yating Lu, Yaxuan Qi, Qingrui Nong, Hao Chen, Ruonan Yu, Alexey Sarapultsev, Xiang Cheng, Shanshan Luo, Desheng Hu","doi":"10.1007/s00395-026-01205-5","DOIUrl":"10.1007/s00395-026-01205-5","url":null,"abstract":"<p><p>Myocardial ischemia/reperfusion (I/R) injury constitutes a major clinical challenge in ischemic heart disease, and ferroptosis has been recognized as a core driver of cardiomyocyte death during reperfusion. However, the upstream regulatory network governing myocardial ferroptosis remains incompletely defined. The mitogen-activated protein kinase 14 (p38α, MAPK14) is a stress-activated kinase critically involved in cardiac pathophysiology, yet its role in I/R-induced ferroptosis remains unclear. Here, we report that p38α deficiency attenuates ferroptosis and protects against myocardial I/R injury by stabilizing c-Myc. Phosphorylated p38α (p-p38α) was significantly elevated in mouse hearts after I/R and in cardiomyocytes following oxygen-glucose deprivation/reperfusion (OGD/R). Cardiomyocyte-specific p38α knockout markedly reduced ferroptosis, myocardial infarct size, and cardiac dysfunction. Mechanistically, p-p38α interacts with c-Myc under I/R stress via key residues Arg291, Arg300, and Lys304 of c-Myc and promotes the recruitment of the E3 ubiquitin ligase STUB1, thereby enhancing ubiquitination at Lys51 (K51) of c-Myc and its proteasomal degradation. Loss of p38α stabilizes c-Myc protein and reverses this process. Furthermore, c-Myc acts as a transcriptional repressor of NCOA4, a core mediator of ferroptosis. I/R-induced downregulation of c-Myc relieves NCOA4 suppression, triggering iron overload, lipid peroxidation, and ferroptosis. Overexpression of c-Myc or inhibition of STUB1 or NCOA4 abolished the pro-ferroptotic effect of I/R. Pretreatment with the p38α inhibitor VX-745 recapitulated the cardioprotective effects by restoring the p38α/c-Myc/NCOA4 axis in vivo. Collectively, our findings identify the p38α/c-Myc/NCOA4 signaling axis as a regulatory cascade governing myocardial I/R-induced ferroptosis. These findings nominate the p38α/c-Myc/NCOA4 axis as a potential therapeutic target in myocardial I/R injury.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"837-862"},"PeriodicalIF":9.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic dependency of malonate protection against cardiac ischemia-reperfusion injury.","authors":"Qian Wang, Xin Hu, Yang Xiao, Rianne Nederlof, Panagiota-Efstathia Nikolaou, Christina Chania, Diane Bakker, Amrita Kim Singh, Markus W Hollmann, Nina C Weber, Bauke Schomakers, Michel van Weeghel, Coert J Zuurbier","doi":"10.1007/s00395-026-01206-4","DOIUrl":"10.1007/s00395-026-01206-4","url":null,"abstract":"<p><p>Malonate, an inhibitor of mitochondrial succinate dehydrogenase (SDH), protects against ischemia-reperfusion injury (IRI) when given at early reperfusion, making it a promising therapeutic agent for acute myocardial infarct (AMI) and stroke patients. Prior to clinical studies, it is essential to identify potential translational roadblocks. One such barrier is the metabolic signature of the heart. Here, we explored whether and how the metabolic signature of the heart drive cardiac IRI and modulate malonate protection. Langendorff-perfused mouse hearts were subjected to 30 min ischemia (I) followed by 90 min reperfusion (R), with or without 5mM disodium malonate administered during the first 5 min reperfusion. Cardiac IRI and malonate protection were examined under four metabolic conditions increasing in metabolic complexity: glucose-only (G), glucose + glutamine (GG), GG + fatty acid (F), F + insulin (Ins). Metabolomic profiling and survival kinases were evaluated at end-ischemia and at 7 min of reperfusion ± malonate. Additional experiments examined the effects of glucose, lactate, and low pH on malonate efficacy. IRI (% infarct size) increased with metabolic complexity: 32 ± 11% (G), 38 ± 11%(GG), 52 ± 14% (F), and 68 ± 10% (Ins). Malonate reduced IS% in the G (-27%), GG (-45%) and F (-23%) groups, but not in the Ins group (-12%, not significant). Malonate increased the glycolytic activator and protectant fructose-1/2,6-bisphosphate, mitochondrially bound hexokinase 1 and ATP across all metabolic conditions, confirming measurements showing cellular malonate uptake in all metabolic conditions. Loss of protection correlated with elevated pre-ischemic glycogen levels, end-ischemic lactate levels and delayed ischemic contracture, both indicative of prolonged glycolysis during ischemia due to glycogen loading, and increased glycolytic intermediates during early reperfusion hallmarks of cardiac glucose loading. Indeed, protection was restored in the insulin group when glucose was withheld prior to ischemia. With glucose present before ischemia, elevated lactate and lower pH were observed at onset reperfusion. Further experiments revealed that lower pH-not elevated lactate-at reperfusion was responsible for the loss of malonate protection. Disodium malonate (120 mg/kg) was also unable to reduce infarct size in an in vivo rat model of cardiac IRI employing similar insulin levels as used in the Langendorff-perfused mouse heart model. While malonate offers robust protection against cardiac IRI across various metabolic environments, its efficacy is compromised under conditions of high ischemic glycogen breakdown, which leads to severe acidosis at the onset of reperfusion that was associated with the loss of malonate protection.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"863-882"},"PeriodicalIF":9.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenteric denervation ameliorates post‑infarction heart failure alongside alterations in the gut-nerve-microbiota axis.","authors":"Zhongqiang Xu, Shengchan Wang, Guirui Sang, Hongxiang Zhang, Yanyan Deng, Xiaodong Teng, Dasheng Lu","doi":"10.1007/s00395-026-01200-w","DOIUrl":"10.1007/s00395-026-01200-w","url":null,"abstract":"<p><p>Sympathetic overactivity and gut microbiota dysbiosis drive chronic heart failure (CHF) progression. This study explored the associations of mesenteric denervation (MDN) with cardioprotection and potential involvement of the nerve-microbiota-heart axis in MI-induced CHF mice. C57BL/6 mice were randomized into control, CHF, and CHF_MDN groups. CHF was induced by LAD ligation, and MDN was performed via phenol ablation of the superior mesenteric artery. MDN was associated with suppressed mesenteric sympathetic activity, improved left ventricular ejection fraction, and reduced myocardial fibrosis and serum BNP. MDN correlated with restoration of colonic tight junction protein expression, reduced myocardial NLRP3 inflammasome activation, and decreased systemic inflammation (LPS, TNF-α, IL-6). 16S rRNA sequencing showed MDN reshaped gut microbiota (decreased F/B ratio, increased facultative anaerobes). Untargeted metabolomics identified 30 differential metabolites in CHF_MDN mice; MDN reduced pro-inflammatory metabolites (hippuric acid, deoxycholic acid) and increased metabolites linked to energy metabolic reprogramming (2-hydroxybutyric acid, ketoleucine, acetylglycine). Integrated analysis revealed that Campylobacterota and Halobacterota (altered by MDN) correlated with sarcosine and linoleic acid. MDN improves cardiac function in MI-induced CHF, alongside inhibition of mesenteric sympathetic activity, restoration of intestinal barrier function, reduction of inflammation, and modulation of gut microbiota and metabolic profiles. These findings suggest the nerve-microbiota-heart axis as a potential therapeutic target.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"895-911"},"PeriodicalIF":9.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-145-5p modulates collagen production and fibroblast behaviour after cardiac injury partially via COL5A1.","authors":"Hong Wang, Jere Paavola, Sanni Perttunen, Katariina Immonen, Ian Hägerström, Suneeta Narumanchi, Karri Kalervo, Johanna Tolva, Juha Sinisalo, Mikko I Mäyränpää, Heikki Ruskoaho, Riikka Kosonen, Vesa M Olkkonen, Mika Laine, Ilkka Tikkanen, Päivi Lakkisto","doi":"10.1007/s00395-026-01199-0","DOIUrl":"10.1007/s00395-026-01199-0","url":null,"abstract":"<p><p>In contrast to humans, zebrafish hearts after cryoinjury undergo transient fibrotic scarring that subsequently resolves and renews with functional cardiomyocytes. To understand the molecular mechanisms underlying cardiac scarring and fibrotic resolution in zebrafish, we investigated cardiac transcriptomic responses in zebrafish at 14 days post-cryoinjury. Principal component analyses revealed distinct transcriptome clusters corresponding to healthy and injured hearts, highlighting significant changes during cardiac regeneration. Gene set enrichment analyses indicated that extracellular matrix organization and inflammatory response pathways were activated in cryoinjured hearts, while mitochondrial organization and oxidative phosphorylation pathways were downregulated. Notably, miR-145-5p was downregulated and col5a1 upregulated in the cryoinjured hearts, contrasting with the expression patterns of miR-145-5p and COL5α1 in the left ventricles of ischemic cardiomyopathy patients. Prediction of miRNA-mRNA interaction and a dual luciferase assay identified COL5A1 as a target of miR-145-5p. Inhibition of miR-145-5p in human cardiac fibroblasts increased COL5A1 and α-SMA, decreased COL1A, and stimulated fibroblast differentiation, proliferation, and migration. Conversely, overexpression of miR-145-5p led to the opposite effects. Downregulation of COL5A1 suppressed fibroblast proliferation and migration, which could be rescued by inhibition of miR-145-5p. Moreover, downregulation of col5a1 attenuated cardiac fibrotic scar resolution in zebrafish. Interestingly, downregulation of COL5A1 or inhibition of miR-145-5p diminished the expression of integrin subunits ITGβ3 and ITGβ5. Furthermore, inhibition of miR-145-5p potentiated the suppression of TGF-β/SMAD signalling and the enhancement of fibroblast proliferation mediated by inhibiting integrin αvβ3 and αvβ5 with cilengitide. Collectively, miR-145-5p modulates collagen production and fibroblast behaviour partially via targeting COL5A1 and through integrin-mediated pathways.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"965-986"},"PeriodicalIF":9.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal neuronal TLR4-induced enhancement of nociceptive signals contributes to myocardial ischemia/reperfusion injury","authors":"Mengyun Dou,Xueying Cheng,Qijing Xing,Jiaxing Wang,Qian Cheng,Weijun Liu,Shijin Xu,Lijun Weng,Biyun Cao,Shufang He,Kang Peng,Ye Zhang,Shiyun Jin","doi":"10.1007/s00395-026-01211-7","DOIUrl":"https://doi.org/10.1007/s00395-026-01211-7","url":null,"abstract":"","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"4 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}