Search Results (2,256)

Background: Uterus transplantation (UTx) is an emerging treatment for absolute uterine factor infertility. However, the use of deceased donors is limited, and donation after circulatory death (DCD) has not yet been utilized. Ischemic injury remains a major barrier, particularly compared with living donor procedures. Hypothermic oxygenated perfusion (HOPE), which has shown protective effects in heart, liver, and kidney transplantation, may offer similar benefits for uterine grafts. Methods: We report the first series applying HOPE to human uteri to improve preservation and enable metabolic injury assessment during perfusion. Six uteri (3 DBD, 3 DCD; median donor age 53 years) underwent 8 h of HOPE following procurement, while paired tissue controls were preserved using static cold storage (SCS). Perfusion was delivered using a pressure-controlled system (15 mmHg, 10 ± 1 °C, VitaSmart^®). Perfusate and tissue samples were analyzed for mitochondrial injury, inflammation, and transcriptional responses. Results: HOPE maintained stable flows (70–150 mL/min), delivered high oxygen levels (pO₂ ≈ 1000 hPa), and increased tissue ATP levels. Stratification based on perfusate flavin mononucleotide (FMN) release identified grafts with greater Complex I/II injury. HOPE was associated with lower levels of mitochondrial injury markers and inflammatory signals, preserved tissue architecture, and promoted gene expression patterns consistent with metabolic recovery compared with paired SCS tissue controls. Conclusions: These findings suggest that HOPE may serve as a preservation approach that enables metabolic and ischemic injury assessment and may facilitate broader use of deceased donor uteri for transplantation. Full article

Open-heart surgery with cardiopulmonary bypass (CPB) is a high-risk procedure with significant morbidity and mortality. CPB, tissue injury, blood loss, endotoxemia and ischemia–reperfusion injury induce a pronounced systemic inflammatory response, leading to endothelial glycocalyx (EG) damage and vascular endothelial dysfunction. Consequently, immune cells, reactive oxygen species, and enzymes gain free access to vascular endothelial cells, resulting in their dysfunction and enhancing inflammation, vascular permeability, and microvascular impairment. EG degradation is most commonly assessed by measuring the circulating levels of its degradation products. Additionally, CPB triggers an early inflammatory response that is characterized by the secretion of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha, and IL-18, which play roles in initiating the process of EG injury. EG damage is further propagated by the sustained release of cytokines, inhibiting the regeneration of the glycocalyx layer. Heparanase and matrix metalloproteinases are enzymatic pathways involved in cytokine-mediated EG degradation after cardiac surgery, and the balance between the pro- and anti-inflammatory cytokines determines the magnitude and duration of the inflammatory response and EG impairment, which correlates with adverse clinical outcomes, including myocardial dysfunction, acute lung and kidney injury, neurological complications, and prolonged need for intensive care. Thus, identifying patients with an exaggerated cytokine response could potentially provide more personalized therapy based on the circulating biomarkers of EG shedding, and cytokine-directed preservation of EG represents a promising therapeutic strategy in vascular dysfunction prevention during and after open-heart surgery. In this review, we summarize the current knowledge on cytokine-mediated EG impairment following open-heart surgery with CPB. Full article

Adipose mesenchymal stem cell-derived exosomes (ADSC-Exo) have demonstrated therapeutic effects in liver diseases and injuries. The Augmenter of Liver Regeneration (ALR), a novel hepatic trophic growth factor, promotes hepatic structural and functional recovery. In this study, we constructed ALR-overexpressing ADSC-Exo (ADSC-ALR-Exo) by harnessing the messaging capacity of ADSC-Exo, and analyzed the effects of ADSC-ALR-Exo on hepatic ischemia–reperfusion injury (IRI) combined with partial hepatectomy in a minipig model. Our results indicated that, compared to the ADSC-Exo group, the ADSC-ALR-Exo group exhibited a significant reduction in reactive oxygen species (ROS) levels, alongside a notable increase in the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Furthermore, there was a marked decrease in malondialdehyde (MDA) content. Concurrently, the concentrations of pro-inflammatory factors in the blood (IL-1β, IL-18, and TNF-α) and liver tissue (IL-1β, IL-18, IL-6, and TNF-α) were significantly lower in the ADSC-ALR-Exo group, while the level of the anti-inflammatory factor IL-10 in the blood was significantly elevated. Additionally, ALR enrichment enhanced the inhibitory effect of ADSC-ALR-Exo on endoplasmic reticulum stress-related pathways, specifically ATF6, IRE1α, and PERK. Compared to ADSC-Exo, the ADSC-ALR-Exo intervention was also more effective in reducing the expression levels of NLRP3, caspase-1, and GSDMD, thereby decreasing the incidence of pyroptosis. In conclusion, ADSC-ALR-Exo mitigated liver injury by inhibiting endoplasmic reticulum stress and cellular pyroptosis induced by liver injury. Full article

Hepatic ischemia–reperfusion injury (IRI) is a major cause of liver damage and is characterized by oxidative stress, inflammatory signaling, and hepatocellular apoptosis. Aim: This study investigated the hepatoprotective effects of agomelatine (AGO) administered before ischemia or at the onset of reperfusion in a hepatic IRI model. Rats were allocated into four experimental groups: Sham, IRI, IRI+AGO, and AGO+IRI. Hepatic ischemia was induced by clamping the hepatic pedicle for 1 h followed by 1 h of reperfusion. AGO (20 mg/kg) was administered orally either before ischemia or at the onset of reperfusion. Oxidative stress markers, antioxidant enzymes, nitric-oxide-related parameters, cytokines, liver injury enzymes, and histopathological changes were evaluated. IRI increased oxidant markers and reduced antioxidant defenses. AGO treatment improved redox balance and antioxidant parameters in both treatment groups, with stronger antioxidant responses observed in the AGO+IRI group. Nitric oxide (NO)-related markers differed among groups, including changes in L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) levels, and interleukin-6 (IL-6) levels decreased following AGO administration, particularly in the AGO+IRI group. Histopathological injury and caspase-3 expression were also attenuated in AGO-treated animals. AGO attenuates hepatic IRI by improving redox balance, modulating NO metabolism, and reducing IL-6–associated signaling and apoptosis, with stronger protection when administered before ischemia. Full article

Aim: This study investigates how Buyang Huanwu Decoction (BHD) protects against cerebral ischemic damage by targeting the NLRP3/Caspase-1 pathway. Methods: The fingerprint of BHD was analyzed by HPLC-UV. Migratory chemicals in BHD-containing cerebrospinal fluid (BHD-CCSF) were analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). The effects of BHD on the NLRP3/Caspase-1 pathway, IL-18 and IL-1β levels in oxygen and glucose deprivation/reperfusion (OGD/R) cells were assessed by Western blot and ELISA. Cerebral infarction severity in permanent middle cerebral artery occlusion (pMCAO) mice was assessed by mNSS scores and staining. Protein and mRNA levels of the NLRP3/Caspase-1 pathway and inflammatory factors (IL-18, IL-1β) were measured. Results: BHD-containing serum (BHD-CS), BHD-CCSF, and Calycosin (Cal) reduced NLRP3, Caspase-1, ASC, GSDMD proteins, IL-18 and IL-1β in OGD/R cells. In pMCAO mice, BHD decreased pathway-related proteins and mRNA and inflammatory factors and alleviated brain injury. Conclusions: BHD ameliorates cerebral ischemia by inhibiting the NLRP3/Caspase-1 pathway, thereby suppressing pyroptosis and inflammation. Full article

Background: Currently, the duration of tourniquet time in total knee arthroplasty is chosen by the surgeons and varies between 0 and 120 min. Studies evaluating the effect of tourniquet time in this surgery are heterogeneous, and there is limited information on molecular/complement profiling. The purpose of this study was, therefore, to determine whether the duration of tourniquet-induced limb ischemia during total knee arthroplasty influences reperfusion injury, resulting in pain, swelling, and the release of pro-inflammatory markers. Methods: In 40 patients undergoing total knee arthroplasty, a tourniquet was applied for up to 30 min (group A, short tourniquet) or 90–120 min (group B, long tourniquet). Postoperative pain and swelling served as primary outcome parameters. The levels of pro- and anti-inflammatory markers before surgery and 4 h, 24 h, and 48 h after surgery were used as secondary outcome parameters for exploratory testing. Results: There were no differences in numeric rating pain scale (NRS) scores and calf circumference between groups A and B. Patients in group B required patient-controlled intravenous analgesia more frequently than group A patients (47% versus 5%, group B vs. group A, p < 0.0001). In group B, a significantly higher increase in C3a and MIG levels between 4 h and 48 h, and a significantly higher increase for MIG and M-CSF between 24 h and 48 h, were observed. Conclusions: Tourniquet times between 90 and 120 min were not associated with higher pain levels or more swelling, but an increased need for intravenous analgesia and a higher increase in pro-inflammatory markers. This might be a consequence of a more pronounced ischemia/reperfusion injury with tourniquet times longer than 90 min. Full article

Myocardial ischemia–reperfusion injury (MIRI) significantly compromises the clinical benefits of revascularization and constitutes a central pathological mechanism worsening prognosis in myocardial infarction patients. Accordingly, dissecting the molecular mechanisms underlying MIRI and formulating effective therapeutic interventions are of great clinical significance. Lycium barbarum polysaccharide (LBP), the primary active constituent of Lycium barbarum, has garnered considerable attention in the prevention and treatment of cardiovascular diseases due to its anti-inflammatory, antioxidant, vasomotor function-improving, and antithrombotic properties. This study aims to investigate the ability of LBP to alleviate MIRI, with a specific focus on its role in modulating the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Myocardial ischemia/reperfusion (I/R) models in rats and hypoxia/reoxygenation (H/R) models in H9c2 cells were established. Myocardial injury and the therapeutic effect of LBP were evaluated by 2,3,5-Triphenyl tetrazolium chloride (TTC) staining, Hematoxylin-eosin (H&E) staining, Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) staining, and Enzyme-linked immunosorbent assay (ELISA). To elucidate the specific mechanism underlying LBP against MIRI, an Nrf2-overexpressing cell line was generated in H9c2 cells, and pharmacological inhibition of Nrf2 with ML385 was applied for complementary validation. The effects of LBP on H/R-induced oxidative stress, inflammatory response (IL-18, IL-1β), and pyroptosis-related protein expression (NLRP3, apoptosis associated speck-like protein containing a CARD (ASC), cysteine-dependent aspartate-specific proteases (caspase)-1, Gasdermin D (GSDMD)) were systematically evaluated. LBP administration conferred robust cardioprotection in I/R rats, as evidenced by a significant reduction in myocardial infarct size, improved preservation of myocardial fiber architecture, and attenuated leakage of cardiac injury biomarkers (lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB)). Mirroring these in vivo findings, LBP pretreatment effectively shielded H9c2 cardiomyocytes from H/R insult, markedly enhancing cell viability while curtailing reactive oxygen species (ROS) accumulation and apoptotic activation. A pivotal finding was the pronounced downregulation of Nrf2 in the H/R group, a deficit that was conclusively reversed by LBP treatment. To decisively establish a causal role for Nrf2, we employed a loss-of-function approach; Nrf2 inhibition completely abrogated the protective benefits of LBP, culminating in exacerbated tissue damage, a surge in ROS, and the upregulation of key pyroptosis effectors (NLRP3, ASC, caspase-1, GSDMD). Conversely, a complementary gain-of-function experiment demonstrated that Nrf2 overexpression alone was sufficient to mimic LBP’s effects, significantly blunting H/R-induced ROS production and pyroptosis. LBP alleviates MIRI by inhibiting pyroptosis through activating the Nrf2/NLRP3 axis, thus representing a promising therapeutic candidate for ischemic heart disease with the potential to improve patient outcomes. Full article

Notably, certain ginsenoside components exhibit distinct bidirectional and context-dependent regulatory effects on ferroptosis depending on the disease setting. In aberrantly proliferating or activated cells, ginsenosides function as ferroptosis inducers, whereas in damaged quiescent cells of normal tissues, they act as ferroptosis inhibitors. The pro-ferroptotic effect is predominantly observed in cells characterized by abnormal proliferation or activation, such as cancer cells and activated hepatic stellate cells in liver fibrosis. In this context, ginsenosides modulate key iron metabolism proteins and suppress antioxidant defense systems (e.g., GPX4, SLC7A11), thereby triggering intracellular iron overload and explosive lipid peroxidation, ultimately culminating in ferroptosis. Conversely, the anti-ferroptotic effect primarily targets damaged non-proliferative cells in normal tissues subjected to pathological insults (e.g., ischemia–reperfusion, inflammation). In this setting, the regulatory focus of ginsenosides shifts toward maintaining iron homeostasis through mechanisms including upregulation of iron storage proteins (e.g., FTH1), downregulation of iron uptake proteins (e.g., TFRC), and inhibition of labile Fe²⁺ accumulation, thereby blocking ferroptosis initiation. This review systematically elucidates the pharmacological effects and underlying mechanisms by which different ginsenoside components regulate ferroptosis across various disease contexts and cell types, with particular emphasis on their disease- and cell type-dependent bidirectional regulatory characteristics. By highlighting these context-specific effects, we aim to provide novel potential therapeutic targets and mechanistic insights for the precision treatment of diverse pathological conditions, including malignant proliferative disorders, non-malignant aberrantly activated/proliferative diseases such as liver fibrosis, and cell injury/degenerative diseases. Full article

Acute kidney injury (AKI) is a major complication of lupus nephritis and kidney transplantation, inevitably causing ischemia–reperfusion (I/R) injury. We previously confirmed that high-dose voclosporin induces drug nephropathy through aberrant peroxisome accumulation. The latter induces increased renal indole-3-aceticT acid (IAA) production due to the decreased expression of the IAA-degrading enzyme indolethylamine N-methyltransferase (INMT). Conversely, INMT overexpression prevents this nephropathy, suggesting that high-dose voclosporin could enable a novel therapeutic approach. This prompted us to test whether INMT overexpression with high-dose voclosporin could avert nephrotoxicity and protect against I/R injury. Inmt-overexpressing mice treated with high-dose voclosporin exhibited absence of peroxisomal abnormalities and resistance to I/R injury. RNA sequencing revealed the downregulation of tubular injury markers NGAL (Lcn2) and KIM-1 (Havcr1) concurrent with significant cytokine suppression. Mechanistic analysis revealed the robust induction of Regnase-2, an mRNA decay factor, which directly targeted stem–loop structures within the 3′ untranslated region of Lcn2 and Havcr1, thereby promoting their degradation in proximal tubular cells. Importantly, Regnase-2 knockdown mice showed Lcn2 upregulation, mitochondrial dysfunction, and peroxisomal abnormalities culminating in AKI, underscoring its renal protective effects. High-dose voclosporin under Inmt overexpression promoted Regnase-2-mediated mRNA decay to suppress tubular injury. This protective effect extended beyond I/R to rhabdomyolysis- and lipopolysaccharide-induced AKI to prevent nephropathy. Our findings demonstrate the potential transformative therapeutic approach of administering high-dose voclosporin to promote the prophylactic effect of Regnase-2 augmentation against AKI in both native and transplanted human kidneys. Full article

Background: Hepatic ischemia–reperfusion (I/R) injury induces systemic oxidative stress and inflammatory responses that may lead to remote lung injury. This study investigated whether taxifolin attenuates hepatic I/R-induced lung damage and examined the involvement of the nuclear factor-κB (NF-κB) and high-mobility group box-1 (HMGB1) signaling axis. Methods: Twenty-eight male Wistar rats were divided into four groups (n = 7): control, taxifolin, hepatic I/R, and taxifolin+I/R. Serum oxidative stress markers (malondialdehyde [MDA], interleukin [IL]-6, total antioxidant/oxidant status [TAS/TOS]) and wet-to-dry lung weight ratio were measured. Lung tissues were evaluated histopathologically and immunohistochemically for NF-κB and HMGB1 expression. Bioinformatics pathway enrichment and molecular docking analyses were also performed. Results: Hepatic I/R significantly increased serum MDA, IL-6, and TOS levels and decreased TAS (p < 0.05). Severe lung injury was observed in the hepatic I/R group (median score: 11), whereas taxifolin pretreatment significantly reduced the injury score (median score: 5, p < 0.001). NF-κB and HMGB1 expression were markedly elevated following hepatic I/R and significantly decreased with taxifolin treatment (p < 0.05). A strong positive correlation was found between NF-κB and HMGB1 expression (r = 0.82, p < 0.001). Pathway enrichment analysis indicated involvement of Toll-like receptor (TLR)-related inflammatory signaling, and docking analysis demonstrated favorable binding of taxifolin to TLR4 and NF-κB p65. Conclusion: Taxifolin attenuated hepatic I/R-induced lung injury by reducing oxidative stress and suppressing HMGB1–TLR4–NF-κB-mediated inflammatory signaling. Full article

Background: Neuronal apoptosis is the core pathological mechanism of cerebral ischemic–reperfusion injury (CIRI); although Astragaloside IV (AS-IV) has demonstrated neuroprotective activity against CIRI, its specific molecular mechanisms underlying the regulation of this apoptosis-related pathway remain to be systematically elucidated. Methods: We establish an in vivo model of middle cerebral artery occlusion/reperfusion (MCAO/R) in rats and an in vitro model of oxygen–glucose deprivation/reperfusion (OGD/R) in PC12 cells. Six core apoptotic proteins, including CytC, Apaf-1, BAX, Bcl-2, Caspase3, and Caspase9, were detected using neurological function scoring, TTC/HE/Nissl staining, TUNEL staining, Western blot, and immunofluorescence techniques. Molecular docking and molecular dynamics simulation were utilized to analyze the binding affinity between AS-IV and the aforementioned apoptotic proteins. Results: Molecular docking and dynamics simulation demonstrated AS-IV stably binds six core apoptotic proteins, and comparative analysis with target-specific reference ligands identified Apaf-1 as its primary target with the most favorable binding properties. In rat MCAO/R models, AS-IV alleviated neurological deficits, reduced cerebral infarct volume and improved brain pathological damage; in PC12 cell OGD/R models, it decreased neuronal apoptosis. Western blot and immunofluorescence confirmed AS-IV downregulated pro-apoptotic proteins (cytoplasmic CytC, Apaf-1, BAX, cleaved-Caspase9/3) and upregulated anti-apoptotic Bcl-2. Conclusions: This study clarifies the anti-apoptotic molecular mechanism of AS-IV, it alleviates CIRI by targeting the CytC/Apaf-1 mitochondrial apoptotic pathway. Full article

Gut ischemia/reperfusion (I/R) injury releases damage-associated molecular patterns (DAMPs), such as extracellular cold-inducible RNA-binding protein (eCIRP). Milk fat globule–epidermal growth factor VIII-derived oligopeptide 3 (MOP3) is a novel peptide enabling macrophage uptake of eCIRP via αvβ3-integrin. MOP3 reduces inflammation in gut I/R, but its mechanisms are not completely understood. We hypothesized MOP3 promotes macrophage polarization toward an anti-inflammatory, M2-like phenotype in gut I/R. We induced gut I/R in mice through 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Intestines were evaluated for macrophage polarization by flow cytometry and immunofluorescence histology. Peritoneal cavity macrophages were isolated from mice and treated with eCIRP, MOP3, α_vβ₃-antibody, and/or naïve IgG for 4 or 24 h. Polarity was assessed by flow cytometry, qPCR, and ELISA. Compared to the sham, the M2 proportion after gut I/R decreased by 22.7%, and the M1 proportion increased by 241%. MOP3 treatment increased the M2 proportion by 64.3%, and the M1 proportion decreased by 22.7%. In eCIRP-stimulated macrophages, MOP3 treatment increased M2-like and reduced M1-like cell-surface markers, gene expression, and cytokine levels. α_vβ₃ antibody dramatically reduced MOP3′s effects. MOP3 promotes M2 polarization through α_vβ₃ integrin-mediated clearance of eCIRP, a novel mechanism whereby MOP3 reduces gut I/R injury. Full article

Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury. Estradiol (E2) and the selective estrogen receptor modulator raloxifene (RAL) reduce organ dysfunction, potentially via heme oxygenase-1 (HO-1)–mediated antioxidant and anti-inflammatory effects. This study examined whether E2 and RAL protect against IRI through G protein-coupled estrogen receptor (GPER)–dependent activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 pathway in ovariectomized (OVX) mice; OVX IRI mice were pretreated for four weeks with E2, RAL, RAL + ML385 (Nrf2 inhibitor), or RAL + G15 (GPER antagonist). Renal histology, inflammatory and oxidative markers, and nuclear Nrf2 levels were assessed; OVX IRI increased interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) and decreased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH); nuclear Nrf2 was low in sham and OVX IRI groups. E2 and RAL improved renal function and histology, reduced inflammation and oxidative stress, restored GPER expression, increased nuclear Nrf2, and upregulated HO-1 and NAD(P)H:quinone oxidoreductase 1 (NQO1). Co-treatment with ML385 or G15 reversed RAL’s benefits, reduced nuclear Nrf2, and worsened injury; E2 and RAL exert renoprotective effects against OVX-related renal IRI in a manner consistent with GPER-dependent Nrf2 nuclear translocation, which suggests involvement of the downstream antioxidant gene activation pathway. Full article

Nateglinide (Nat) is an oral antidiabetic agent of the meglitinide class that has been reported to exert protective effects beyond glycemic control, particularly against oxidative stress and inflammation. Since oxidative stress and inflammation play a key role in the pathogenesis of acute kidney injury (AKI), especially following ischemia/reperfusion (I/R), this study aimed to evaluate the potential renoprotective effects of Nat in a rat model of I/R-induced AKI. Forty male Sprague Dawley rats were randomly divided into four groups (n = 10): Control, I/R, I/R + Nat (50 mg/kg), and I/R + Nat (100 mg/kg). Bilateral renal ischemia was induced by clamping renal arteries for 45 min, followed by 24 h of reperfusion. Nat was administered orally 1 h before ischemia. Renal levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and thiobarbituric acid reactive substances (TBARSs) were assessed. Serum blood urea nitrogen (BUN), creatinine, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were also measured, and histopathological analyses were performed. Nat significantly increased renal antioxidant parameters and reduced TBARS levels. Moreover, Nat markedly decreased serum BUN, creatinine, TNF-α, and IL-1β levels compared with the I/R group (p < 0.05). Histopathology confirmed attenuated renal damage in Nat-treated groups (p < 0.0001). These results indicate that Nat confers significant renoprotection against renal I/R injury via suppression of oxidative stress and inflammation. Full article

Two-pore domain potassium (K₂P) channels are the most recently identified family of potassium channels. They are regarded as the largest group of background “leak” channels, encoded by 15 mammalian KCNK genes, and divided into six subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). These channels have a role in stabilizing the resting membrane potential. Their widespread presence in the heart and vasculature supports cellular homeostasis by regulating cardiac rhythm, vascular tone, and protection against ischemic stress. The TASK, TWIK, and TREK subfamilies are the most abundantly expressed K₂P channel subfamilies in the cardiovascular system, and dysregulation of specific members has been strongly linked to the development of major cardiovascular diseases. Mutations in TASK-1 have been identified in patients with pulmonary arterial hypertension, providing human genetic evidence linking K₂P dysfunction to pulmonary vascular disease. While alterations in other K₂P channels, such as TREK-1, have been demonstrated in preclinical studies where reduced channel activity is associated with ischemia–reperfusion injury and promotes cardiac arrhythmias. Growing evidence suggests that K₂P channels could serve as promising therapeutic targets, with pharmacological activation of TASK-1 and TREK-1, for instance, that might help restore vascular tone, reduce remodeling, and offer cardioprotection. Their unique leak-channel properties enable the development of highly selective treatments. This review addresses the molecular biology, physiological roles, and disease relevance of K₂P channels in the cardiovascular and pulmonary systems, emphasizing their potential as targets for innovative therapies in cardiovascular diseases. Full article