Basic Research in Cardiology最新文献

{"title":"Effects of SGLT2 inhibitors on ion channels in heart failure: focus on the endothelium.","authors":"Mengnan Wang,Benedikt Preckel,Coert J Zuurbier,Nina C Weber","doi":"10.1007/s00395-025-01115-y","DOIUrl":"https://doi.org/10.1007/s00395-025-01115-y","url":null,"abstract":"Heart failure (HF) is a life-threatening cardiovascular disease associated with high mortality, diminished quality of life, and a significant economic burden on both patients and society. The pathogenesis of HF is closely related to the endothelium, where endothelial ion channels play an important role in regulating intracellular Ca2+ signals. These ion channels are essential to maintain vascular function, including endothelium-dependent vascular tone, inflammation response, and oxidative stress. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown promising cardiovascular benefits in HF patients, reducing mortality risk and hospitalization in several large clinical trials. Clinical and preclinical studies indicate that the cardioprotective effects of SGLT2i in HF are mediated by endothelial nitric oxide (NO) pathways, as well as by reducing inflammation and reactive oxygen species in cardiac endothelial cells. Additionally, SGLT2i may confer endothelial protection by lowering intracellular Ca2+ level through the inhibition of sodium-hydrogen exchanger 1 (NHE1) and sodium-calcium exchanger (NCX) in endothelial cells. In this review, we discuss present knowledge regarding the expression and role of Ca2+-related ion channels in endothelial cells in HF, focusing on the effects of SGLT2i on endothelial NHE1, NCX as well as on vascular tone.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"25 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945457","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":"CD163+ macrophages attenuate pressure overload-induced left ventricular systolic dysfunction and cardiac mitochondrial dysfunction via interleukin-10","authors":"Wei Ni, Xiaofeng Ge, Yang Liu, Jingyu Chen, Lin Wang, Linjian Chen, Zhaokai Li, Peng Zhang, Shufen Huang, Junhui Xu, Le Zhang, Xiabin Fan, Gang Wang, Wei Huang, Yuanchao Ye, Jiancang Zhou, Cuilian Dai, Binbin Liu","doi":"10.1007/s00395-025-01114-z","DOIUrl":"https://doi.org/10.1007/s00395-025-01114-z","url":null,"abstract":"<p>Macrophage depletion exacerbates pressure overload-induced heart failure, but therapeutic translation is hindered by macrophage subset heterogeneity. The functional role of CD163⁺ macrophages in heart failure remains unclear. Transverse aortic constriction (TAC) was employed to induce pressure overload. <i>Cd163</i>^−/− mice exhibited significantly aggravated TAC-induced left ventricular systolic dysfunction, as demonstrated by reduced ejection fraction, fractional shortening, and global longitudinal strain, compared to wild-type (WT) controls. RNA sequencing of cardiac tissues revealed significant differential gene expression between TAC-treated WT and <i>Cd163</i>^−/− mice, especially in pathways governing mitochondrial bioenergetics and homeostasis. Transmission electron microscopy confirmed greater accumulation of dysfunctional mitochondria in cardiomyocytes of <i>Cd163</i>^−/− mice relative to WT following TAC. Additionally, the proportion of CD163⁺ macrophages among cardiac macrophages increased post-TAC. Serum IL-10 levels and cardiac macrophage IL-10 expression were significantly diminished in <i>Cd163</i>^−/− mice compared to WT after TAC. IL-10 supplementation effectively reversed the TAC-induced impairment in left ventricular systolic function in both WT and <i>Cd163</i>^−/− mice, and reduced NADH/NAD⁺ ratios, reduced mitochondrial dysfunction, and improved mitochondrial membrane potential in <i>Cd163</i>^−/− mice. Cross-sectional clinical data supported these findings, showing decreased IL-10 levels as a significant risk factor for heart failure in hypertensive patients (odds ratio: 0.397; 95% CI 0.203–0.775; p = 0.007). Collectively, these results highlight the protective role of CD163⁺ macrophages against pressure overload-induced left ventricular dysfunction and mitochondrial dysfunction through IL-10-dependent pathways.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"75 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926602","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":"A new mechanism of high-altitude adaptation reducing myocardium infarction: inhibiting inflammation-induced ubiquitin degradation of BKCa to enhance coronary vasodilation.","authors":"Sen Wang,Yu Zhang,Wei-Cheng Yuan,Can-Yang Qi,Hua-Xing Zhang,Tian-Qi Wang,Hui-Jie Liu,Hai-Shuang Li,Yan-Ming Tian,Sheng Wang,Sui-Bing Miao,Li-Ping Zhang,Hui Guo,Xiang-Jian Zhang,Yi Zhang,Huijie Ma,Yue Guan","doi":"10.1007/s00395-025-01113-0","DOIUrl":"https://doi.org/10.1007/s00395-025-01113-0","url":null,"abstract":"Our prior research demonstrated that chronic intermittent hypobaric hypoxia (CIHH) pretreatment confers cardioprotection against ischemia/reperfusion (I/R) injury in rats. However, the precise mechanisms underlying CIHH's cardioprotective effects remain insufficiently understood. This study aims to elucidate the upstream signaling pathways and dynamic regulation of BKCa channels in mediating CIHH-induced cardioprotection through coronary artery vasodilation in rats. Male Sprague-Dawley rats, matched by age and body weight, were assigned to control (Con) and CIHH groups. The CIHH group underwent 35 days of hypobaric hypoxia exposure simulating an altitude of 4000 m, for 5 h daily. Hearts were isolated, perfused using the Langendorff system, and subjected to 30 min of ischemia, followed by 60 or 120 min of reperfusion. Compared to the Con group, CIHH significantly improved left ventricular function recovery, reduced infarct size, and increased coronary flow (CF). Microvessel recording, co-immunoprecipitation, and whole-cell patch clamp techniques demonstrated that CIHH augmented CF by promoting coronary vasodilation, attributed to the inhibition of muscle RING-finger protein-1 (MuRF1)-mediated degradation of the BKCa-β1 subunit. Moreover, CIHH inhibited IKKα-induced phosphorylation and ubiquitin-mediated degradation of IκBα, thereby enhancing its cytoplasmic binding to NF-κB p65 in coronary smooth muscle cells. This process attenuated NF-κB p65 nuclear translocation and the subsequent inflammation-induced expression of MuRF1. The observed increase in coronary vasodilation, driven by the suppression of NF-κB/MuRF1-mediated BKCa-β1 degradation, contributes to enhanced CF and cardioprotection against I/R injury following CIHH.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"115 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915151","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":"The cGAS-STING pathway promotes acute ischemia-induced neutropoiesis and neutrophil priming in the bone marrow","authors":"Jiankun Zhu, Xinjia Ruan, MariaSanta C. Mangione, Pablo Parra, Guo Chen, Xiaoping Su, Xiang Luo, Dian J. Cao","doi":"10.1007/s00395-025-01111-2","DOIUrl":"https://doi.org/10.1007/s00395-025-01111-2","url":null,"abstract":"<p>Our previous work demonstrated that the DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) negatively affects post-infarct repair by promoting pro-inflammatory macrophages. However, whether cGAS and its downstream partner STING (Stimulator of Interferon Genes) regulate neutrophil production and function in the context of acute myocardial ischemia remains unclear. This study investigated the role of the cGAS-STING pathway in neutropoiesis (neutrophil production and differentiation) and examined whether ischemia primes neutrophils in the bone marrow via this pathway, enhancing their functionality and contributing to cardiac inflammatory injury. Using myocardial infarction (MI) models in wild-type (WT), <i>Cgas</i>^−/−, and <i>Sting</i>^−/− mice, we analyzed neutrophils from the bone marrow, peripheral blood, and infarcted tissue. Additionally, we generated neutrophil-specific conditional knockouts of <i>Cgas</i> and performed adoptive transfer experiments with <i>Cgas</i>-deficient neutrophils. RNA sequencing revealed that ischemia increased neutrophil production in the bone marrow and activated pathways involved in cytokine signaling, phagocytosis, chemotaxis, and degranulation. Inhibiting the cGAS-STING pathway reduced neutrophil production by decreasing lineage committed neutrophil precursors including early neutrophil precursors (eNP) and preNeu and downregulated ischemia-induced pathways. Neutrophil conditional <i>Cgas</i> deletion or adoptive transfer of <i>Cgas</i>-deficient neutrophils improved survival but did not significantly impact ischemia-induced remodeling. In conclusion, we demonstrate for the first time that ischemia enhanced neutrophil functionality before recruitment to infarcted tissue, and the cGAS-STING pathway played an important role in neutrophil production and priming. Furthermore, our findings demonstrate a neutrophil-specific role of cGAS in promoting cardiac rupture and mortality in MI. This study provides a more comprehensive understanding of the cGAS-STING pathway in acute ischemia and may support the translation of cGAS-STING modulators, an emerging therapeutic field.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"63 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920309","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":"Altered protein homeostasis in cardiovascular diseases contributes to Alzheimer's-like neuropathology.","authors":"Nirjal Mainali,Meenakshisundaram Balasubramaniam,Sonu Pahal,W Sue T Griffin,Robert J Shmookler Reis,Srinivas Ayyadevara","doi":"10.1007/s00395-025-01109-w","DOIUrl":"https://doi.org/10.1007/s00395-025-01109-w","url":null,"abstract":"Cardiovascular diseases (CVDs) are the leading cause of death worldwide. CVD is known to increase the risk of subsequent neurodegeneration but the mechanism(s) and proteins involved have yet to be elucidated. We previously showed that myocardial infarction (MI), induced in mice and compared to sham-MI mice, leads to increases in protein aggregation, endoplasmic reticulum (ER) stress in both heart and brain, and changes in proteostatic pathways. In this study, we further investigate the molecular mechanisms altered by induced MI in mice, which were also implicated by proteomics of postmortem human hippocampal aggregates from Alzheimer's disease (AD) and cardiovascular disease (CVD) patients, vs. age-matched controls (AMC). We utilized intra-aggregate crosslinking to identify protein-protein contacts or proximities, and thus to reconstruct aggregate \"contactomes\" (nonfunctional interactomes). We used leave-one-out analysis (LOOA) to determine the contribution of each protein to overall aggregate cohesion, and gene ontology meta-analyses of constituent proteins to define critical organelles, processes, and pathways that distinguish AD and/or CVD from AMC aggregates. We identified influential proteins in both AD and CVD aggregates, many of which are associated with pathways or processes previously implicated in neurodegeneration such as mitochondrial, oxidative, and endoplasmic-reticulum stress; protein aggregation and proteostasis; the ubiquitin proteasome system and autophagy; axonal transport; and synapses.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"65 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915149","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":"Reinstating respiratory heart rate variability improves hemodynamic responses during exercise in heart failure with reduced ejection fraction","authors":"Julia Shanks, Mridula Pachen, Nigel A. Lever, Julian F. R. Paton, Rohit Ramchandra","doi":"10.1007/s00395-025-01110-3","DOIUrl":"https://doi.org/10.1007/s00395-025-01110-3","url":null,"abstract":"<p>Individuals with heart failure have significantly reduced exercise capacity, a critical life-limiting symptom for those living with the disease. Heart failure is negatively correlated with decreased heart rate variability, including the loss of heart rate variability in tune with breathing—termed respiratory heart rate variability (RespHRV). We tested the hypothesis that restoration of RespHRV would improve exercise tolerance. Heart failure was induced in adult female sheep using a microembolization technique, and the sheep were divided into two groups: RespHRV paced and monotonically paced. Following a 1-week baseline recording, the sheep underwent 2 weeks of pacing. Direct recordings of hemodynamic parameters, including arterial pressure, cardiac output, coronary artery blood flow, and heart rate, were taken at rest and during treadmill exercise. Reinstating RespHRV significantly increased resting cardiac output, a change not observed in monotonically paced sheep. Neither group showed a change in resting coronary artery blood flow. During exercise, RespHRV-paced sheep showed increased cardiac output, coronary artery blood flow, cardiac power output, and faster heart rate recovery post-exercise. In contrast, monotonically paced sheep showed no changes in exercise-induced cardiac function. A separate group of heart failure animals were studied to determine if these benefits would persist alongside heart failure medications. RespHRV pacing continued to improve resting cardiac output with concurrent heart failure medications. Our results indicate that reinstating RespHRV may be a novel approach for improving outcomes in heart failure, including exercise capacity.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"15 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901260","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":"A new model of heart failure with preserved ejection fraction induced by metabolic syndrome in Ossabaw miniature swine","authors":"Xian-Liang Tang, Mouhamad Alloosh, Qinghui Ou, Li Luo, Devendra K. Agrawal, Dinesh K. Kalra, Michael Sturek, Roberto Bolli","doi":"10.1007/s00395-025-01112-1","DOIUrl":"https://doi.org/10.1007/s00395-025-01112-1","url":null,"abstract":"<p>A major obstacle to progress in heart failure with preserved ejection fraction (HFpEF) is the paucity of clinically relevant animal models. We developed a large, translationally relevant model in Ossabaw minipigs, which are genetically predisposed to the metabolic syndrome (MetS). Pigs were fed a “Western diet” high in calories, fructose, fat, cholesterol, and salt and received 1–2 deoxy-corticosterone acetate (DOCA) depots (n = 10). After 6 months, they exhibited liver function abnormalities and marked increases in body weight, arterial blood pressure, serum cholesterol and triglycerides, and plasma glucose and insulin levels (glucose tolerance test), indicating the development of a full MetS. Echocardiography demonstrated no change in LV ejection fraction but progressive concentric LV hypertrophy and left atrial dilatation. Doppler echocardiography showed increased E/e’ ratio and increased peak early (E) and peak late atrial (A) transmitral inflow velocities, with no change in E/A ratio. Right heart catheterization demonstrated increased central venous pressure, pulmonary arterial systolic pressure, and pulmonary capillary wedge pressure. Clinically, pigs exhibited impaired exercise capacity, assessed by treadmill tests, associated with chronotropic incompetence. Pathologic examination showed significant myocardial fibrosis, myocyte hypertrophy, and liver fibrosis. In contrast, lean pigs fed a standard diet (n = 3) did not show any changes at 6 months. The Ossabaw porcine model described herein is unique in that it recapitulates the entire constellation of major multiorgan comorbidities and hemodynamic, clinical, and metabolic features of MetS-driven human HFpEF: obesity, arterial hypertension, hyperlipidemia, glucose intolerance, insulin resistance, liver fibrosis and dysfunction, pulmonary hypertension, increased LV filling pressures, concentric LV hypertrophy, LV diastolic dysfunction with preserved systolic function, and impaired exercise capacity. Because of its high clinical relevance, this model is well-suited for exploring the pathophysiology of MetS-driven HFpEF and the efficacy of new therapies.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"44 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898052","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":"Tyrosine phosphorylation of Kir6.2 subunit negatively regulates cardiac KATP channel activity","authors":"Yating Zhi, Bin Yang, Jianyi Huo, Haojie Wang, Bo Yang, Ya-Feng Zhou, Fei Xiao, Hua-Qian Yang","doi":"10.1007/s00395-025-01108-x","DOIUrl":"https://doi.org/10.1007/s00395-025-01108-x","url":null,"abstract":"<p>The plasma membrane ATP-sensitive potassium (K_ATP) channel in cardiac myocytes plays a critical role in protecting the heart against ischemic injury. Post-translational modifications regulate K_ATP channel activity and play a role in cardioprotection. However, the role of tyrosine phosphorylation in K_ATP channel regulation remains unclear. In this study, we investigated the cardiac K_ATP channel subtype Kir6.2/SUR2A and demonstrated that a protein tyrosine kinase inhibitor significantly increased the current amplitude through blunting the ATP sensitivity of K_ATP channels without altering the single-channel current or the channel surface expression. Mutation screening identified Y258 in the Kir6.2 subunit as the tyrosine phosphorylation site of the K_ATP channel. In cardiomyocytes, K_ATP channel currents can be reversibly enhanced or weakened by inhibiting the tyrosine kinase epidermal growth factor receptor or the protein tyrosine phosphatase 1B. Furthermore, in a perfused mouse heart model, the inhibitor of epidermal growth factor receptor exhibited a significant cardioprotective effect in a K_ATP channel dependent manner, indicating the pharmacological potential for treatment of ischemic heart disease.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"34 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849703","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":"Impact of chronic hyperglycaemia on the coronary microcirculation – benefits of targeting IL-36 and diet reversal","authors":"Juma El-Awaisi, Dean Kavanagh, Silke Heising, Ina Maria Schiessl, Simon J. Cleary, David J. Hodson, Neena Kalia","doi":"10.1007/s00395-025-01107-y","DOIUrl":"https://doi.org/10.1007/s00395-025-01107-y","url":null,"abstract":"<p>Following myocardial infarction (MI), patients with type 2 diabetes mellitus (T2DM) have poorer prognosis which may be linked to increased susceptibility of coronary microvessels to injury. Interleukin-36 (IL-36) may mediate this injury but its role in the microcirculation of the chronically hyperglycaemic injured heart is unknown. Intravital and laser speckle imaging of the anaesthetised mouse beating heart evaluated the impact of a 16-week high fat diet (HFD)-induced hyperglycaemia ± myocardial ischaemia–reperfusion injury (IR) injury on coronary microvessels. Neutrophil/platelet recruitment, neutrophil extracellular trap formation, cellular necrosis, vascular leakage, vascular tonal changes, functional capillary density, overall ventricular perfusion and levels of circulating inflammatory cytokines were assessed alongside the vasculoprotective ability of an IL-36 receptor antagonist (IL-36Ra). Whether heightened microvessel damage in injured HFD mice was permanent or reversible was investigated after normalising hyperglycaemia through diet reversal (DR). Microcirculatory events assessed were perturbed basally in HFD mice and further after injury. IL-36Ra mitigated these effects and improved infarct size. DR was also beneficial, decreasing neutrophil recruitment to levels below those seen in untreated mice. Mechanistically, benefits of both IL-36Ra and DR could be explained by decreased endothelial oxidative stress and VCAM-1 expression and possibly by raised levels of IL-4/IL-13. Basal changes in chronically hyperglycaemic coronary microvessels that are heightened in the aftermath of reperfusion may explain the poorer outcomes in MI patients with T2DM. These findings are the first to highlight the specific benefits of IL-36 inhibition and reversing hyperglycaemia through dietary modification on the coronary microcirculation in a preclinical model of T2DM.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"26 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841326","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":"Triiodothyronine protects infarcted myocardium by reducing apoptosis and preserving mitochondria","authors":"Domenico Cerullo, Polyxeni Mantzouratou, Angelo M. Lavecchia, Melissa Balsamo, Daniela Corna, Laura Brunelli, Christodoulos Xinaris","doi":"10.1007/s00395-025-01106-z","DOIUrl":"https://doi.org/10.1007/s00395-025-01106-z","url":null,"abstract":"<p>Myocardial infarction (MI) is a leading cause of heart failure, with thyroid hormone (TH) signaling playing a key role in heart function and postinfarct recovery. Despite evidence of TH administration's safety in cardiac patients, inconsistent therapeutic outcomes and limited understanding of its mechanisms hinder clinical translation. This study aims to investigate the long-term effect of acute triiodothyronine (T3) administration following MI and to elucidate the mechanisms of its cardioprotective actions. To this end, two doses (40 μg/kg) of T3 were administered immediately after injury and 24 h later in a cryoinjury mouse model of left ventricle (LV) infarction. Remarkably T3 administration significantly reduced scar expansion. Echocardiographic analysis conducted 28 days post-injury revealed that T3 administration improved LV remodeling and prevented LV hypertrophy. At molecular level, T3 administration strongly reduced apoptosis in the peri-infarcted area, without inducing cardiac cell proliferation. Furthermore, T3 prevented the accumulation of long-chain acylcarnitines and the subsequent mitochondrial damage. These findings demonstrate that acute T3 treatment following MI improves long-term LV function and reduces LV remodeling by limiting apoptosis in the peri-infarct region and by preserving mitochondrial function and structural integrity.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"23 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832024","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}