Search Results (62)

Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. While timely reperfusion therapies such as percutaneous coronary intervention (PCI) and thrombolysis are essential for salvaging ischemic myocardium, they can paradoxically exacerbate tissue injury through a process known as myocardial infarction reperfusion injury (MIRI). MIRI can contribute to up to 50% of the final infarct size, significantly diminishing the benefits of revascularization and leading to worsened cardiac outcomes. The pathophysiology of MIRI involves complex, interrelated mechanisms including oxidative stress, calcium overload, mitochondrial dysfunction, inflammatory responses, apoptosis, and dysregulated autophagy. Post-reperfusion recovery is further complicated by structural and functional abnormalities such as microvascular obstruction, endothelial dysfunction, and myocardial stunning. Clinically, distinguishing reperfusion injury from ischemic damage is challenging and often requires the use of sensitive biomarkers, such as cardiac troponins, alongside advanced imaging modalities. Although a range of pharmacological (e.g., antioxidants, calcium channel blockers, mitochondrial stabilizers, anti-inflammatory agents) and non-pharmacological (e.g., hypothermia, gene therapy, stem cell-based therapies) interventions have shown promise in preclinical studies, their clinical translation remains limited. This is largely due to the multifactorial and dynamic nature of MIRI. In this context, network pharmacology offers a systems-level approach to understanding the complex biological interactions involved in MIRI, facilitating the identification of multi-target therapeutic strategies. Integrating network pharmacology with omics technologies and precision medicine holds potential for advancing cardioprotective therapies. This review provides a comprehensive analysis of the molecular mechanisms underlying MIRI, examines the current clinical challenges, and explores emerging therapeutic strategies. Emphasis is placed on bridging the translational gap through validated, multi-target approaches and large-scale, multicenter clinical trials. Ultimately, this work aims to support the development of innovative and effective interventions for improving outcomes in patients with myocardial infarction. Full article

Hypertension-induced cardiac remodeling is a complex process driven by interconnected molecular and cellular mechanisms that culminate in hypertensive myocardium, characterized by ventricular hypertrophy, fibrosis, impaired angiogenesis, and myocardial dysfunction. This review discusses the histomorphometric changes in capillary density, fibrosis, and mast cells in the hypertensive myocardium and delves into the roles of key regulatory systems, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathways, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling in the pathogenesis of hypertensive heart disease (HHD). Capillary rarefaction, a hallmark of HHD, contributes to myocardial ischemia and fibrosis, underscoring the importance of maintaining vascular integrity. Targeting capillary density (CD) through antihypertensive therapy or angiogenic interventions could significantly improve cardiac outcomes. Myocardial fibrosis, mediated by excessive collagen deposition and influenced by fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-β), plays a pivotal role in the structural remodeling of hypertensive myocardium. While renin–angiotensin–aldosterone system (RAAS) inhibitors show anti-fibrotic effects, more targeted therapies are needed to address fibrosis directly. Mast cells, though less studied in humans, emerge as critical regulators of cardiac remodeling through their release of pro-fibrotic mediators such as histamine, tryptase, and FGF-2. The apelinergic system emerges as a promising therapeutic target due to its vasodilatory, anti-fibrotic, and cardioprotective properties. The system counteracts the deleterious effects of the RAAS and has demonstrated efficacy in preclinical models of hypertension-induced cardiac damage. Despite its potential, human studies on apelin analogs remain limited, warranting further exploration to evaluate their clinical utility. VEGF signaling plays a dual role, facilitating angiogenesis and compensatory remodeling during the early stages of arterial hypertension (AH) but contributing to maladaptive changes when dysregulated. Modulating VEGF signaling through exercise or pharmacological interventions has shown promise in improving CD and mitigating hypertensive cardiac damage. However, VEGF inhibitors, commonly used in oncology, can exacerbate AH and endothelial dysfunction, highlighting the need for therapeutic caution. The NO/NOS pathway is essential for vascular homeostasis and the prevention of oxidative stress. Dysregulation of this pathway, particularly endothelial NOS (eNOS) uncoupling and inducible NOS (iNOS) overexpression, leads to endothelial dysfunction and nitrosative stress in hypertensive myocardium. Strategies to restore NO bioavailability, such as tetrahydrobiopterin (BH₄) supplementation and antioxidants, hold potential for therapeutic application but require further validation. Future studies should adopt a multidisciplinary approach to integrate molecular insights with clinical applications, paving the way for more personalized and effective treatments for HHD. Addressing these challenges will not only enhance the understanding of hypertensive myocardium but also improve patient outcomes and quality of life. Full article

(1) Background: Doxorubicin (DOX) is a frontline chemotherapeutic, but its side-effects from oxidative stress, leading to cardiotoxicity, pose significant challenges to its clinical use. We recently discovered a novel family of proteolysis-resistant, cystine-dense, and cell-penetrating microproteins from Panax ginseng that we term ginsentides. Ginsentides, such as the 31-residue TP1, coordinate multiple biological systems to prevent vascular dysfunction and endoplasmic reticulum stress induced by internal and external stressors. (2) Methods: We assessed the protective effects of ginsentide TP1 on DOX-induced cardiotoxicity using both in vitro functional studies on H9c2 cardiomyocytes and in vivo animal models by zebrafish and ICR mouse models. In these models, we examined oxidative stress, apoptosis, intracellular calcium levels, mitochondrial function, inflammatory responses, and cardiac function. (3) Results: We show that ginsentide TP1 protects against DOX-induced cytotoxicity in the mitochondria-rich H9c2 cardiomyocytes and reduces myocardial injury in zebrafish and mice by mitigating oxidative stress, inflammation, calcium, and mitochondrial dysfunction, as well as apoptosis-mediated cell death. Importantly, TP1 preserves cellular homeostasis without compromising the anticancer potency of DOX in breast cancer cells. (4) Conclusions: our findings highlight a specific antioxidative function of ginsentide TP1 in managing DOX-induced cardiotoxicity during cancer treatment and provide a promising lead for developing cardioprotective peptides and microproteins against oxidative stress. Full article

After weaning, piglets no longer consume breast milk, and their immune system is not yet fully developed. At this time, if weaned piglets are infected with E. coli, their subsequent growth will be seriously affected. In the present study, 48 healthy 28-day-old weaned piglets (6.65 ± 1.19 kg, Duroc × Landrace × Large White) were randomly divided into an LPS group and control group. Piglets in the LPS group were intraperitoneally injected with an LPS solution (LPS was dissolved in sterile saline to form a solution of 100 μg/mL and injected at a dose of 1 mL per kilogram of body weight) for 13 consecutive days. Piglets in the control group were injected with the same volume of sterile saline. On days 1, 5, 9, and 13 of the experiment, six piglets from each group were randomly selected for dissection, the blood and heart samples were collected, and then cardiac function-related indicators were detected. A portion of the heart tissue was fixed in 4% paraformaldehyde and further used to make paraffin sections; then, hematoxylin–eosin (H&E) staining was performed. Masson staining was used to detect the changes in collagen fibers in the hearts. The other parts of the heart tissues were frozen in liquid nitrogen and stored in a refrigerator at −80 °C for the detection of tissue antioxidant indices. The mRNA expression levels of the toll-like receptor 4 (TLR4) signaling pathway, transforming growth factor-β (TGF-β) signaling pathway, and inflammatory cytokines in heart tissues were detected by real-time PCR. The results showed that catalase (CAT) and superoxide dismutase (SOD) contents in the heart tissue homogenates increased significantly on days 1 and 5 in LPS-induced piglets (p < 0.01, p < 0.05), while total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) contents decreased significantly on day 5 (p < 0.05). On day 5, the contents of serum cardiac function indicators lactate dehydrogenase (LDH), creatine kinase isoenzymes (CK-MB), and cardiac troponin I (cTn-I) were significantly increased in LPS-induced piglets (p < 0.01). On the 1st and 5th days, the heart tissue showed obvious pathological damage, which was manifested as the disordered arrangement of myocardial fibers, depression of myocardial cells, infiltration of inflammatory factors, congestion of capillaries, and significant increase in cardiac collagen fibers. On the 1st day, the mRNA expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were significantly increased in LPS-induced piglets with heart injury (p < 0.01). On the 5th day, the mRNA expression levels of the TLR4 signaling pathway [TLR4, myeloid differentiation primary response gene 88 (MyD88), nuclear factor kappa-B (NF-κB)], TNF-α, and interleukin 10 (IL-10) were also significantly increased in LPS-induced piglets with heart injury (p < 0.01, p < 0.05). The mRNA expression levels of the TGF-β signaling pathway (TGF-β, Smad2, and Smad4) in cardiac fibrosis-related genes were significantly increased on days 5 and 9 (p < 0.01, p < 0.05). The mRNA expression levels of Smad3 and Smad7 in cardiac fibrosis-related genes were also significantly increased on day 9 (p < 0.01). These results indicate that oxidative stress occurs in the heart tissue of LPS-induced piglets on the 1st and 5th days, leading to cardiac tissue damage. However, on the 9th and 13th days, the degree of heart damage in the piglets was less than that on the 1st and 5th days, which may be due to the tolerance of piglets’ tissues and organs because of multiple same-dose LPS stimulations. Full article

There is increasing evidence demonstrating that psychiatric conditions elevate the risk of developing accelerated atherosclerosis and early-onset cardiovascular disease (CVD), including myocardial infarction (MI). Several mechanisms contribute to this observation. The dysfunction of the autonomic nervous system and hyperactivity of the hypothalamic–pituitary–adrenal axis in these patients contribute to the development of MI. Additionally, patients with underlying psychiatric disorders often have abnormal levels of anti-inflammatory and pro-inflammatory cytokines, which can lead to early vascular damage and subsequent atherosclerosis. Elevated PAI-1 levels, reduced tPA activity, and the decreased brain-derived neurotrophic factor (BDNF), influenced by coagulation and inflammation, may contribute to depression and its link to MI. Oxidative stress, marked by increased reactive species and impaired antioxidant defenses, is associated with cellular damage and has been consistently implicated in schizophrenia and bipolar disorder, potentially contributing to myocardial infarction. Finally, molecular genetic studies have indicated that psychiatric disorders and myocardial infarction may share potential pleiotropic genes. The interplay between the psychiatric conditions and myocardial infarction underscores the importance of integrated care approaches to manage both mental and physical health. Full article

Delayed reperfusion of the ischemic heart (I/R) is known to impair the recovery of cardiac function and produce a wide variety of myocardial defects, including ultrastructural damage, metabolic alterations, subcellular Ca²⁺-handling abnormalities, activation of proteases, and changes in cardiac gene expression. Although I/R injury has been reported to induce the formation of reactive oxygen species (ROS), inflammation, and intracellular Ca²⁺ overload, the generation of oxidative stress is considered to play a critical role in the development of cardiac dysfunction. Increases in the production of superoxide, hydroxyl radicals, and oxidants, such as hydrogen peroxide and hypochlorous acid, occur in hearts subjected to I/R injury. In fact, mitochondria are a major source of the excessive production of ROS in I/R hearts due to impairment in the electron transport system as well as activation of xanthine oxidase and NADPH oxidase. Nitric oxide synthase, mainly present in the endothelium, is also activated due to I/R injury, leading to the production of nitric oxide, which, upon combination with superoxide radicals, generates nitrosative stress. Alterations in cardiac function, sarcolemma, sarcoplasmic reticulum Ca²⁺-handling activities, mitochondrial oxidative phosphorylation, and protease activation due to I/R injury are simulated upon exposing the heart to the oxyradical-generating system (xanthine plus xanthine oxidase) or H₂O₂. On the other hand, the activation of endogenous antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and the concentration of a transcription factor (Nrf2), which modulates the expression of various endogenous antioxidants, is depressed due to I/R injury in hearts. Furthermore, pretreatment of hearts with antioxidants such as catalase plus superoxide dismutase, N-acetylcysteine, and mercaptopropionylglycerine has been observed to attenuate I/R-induced subcellular Ca²⁺ handling and changes in Ca²⁺-regulatory activities; additionally, it has been found to depress protease activation and improve the recovery of cardiac function. These observations indicate that oxidative stress is intimately involved in the pathological effects of I/R injury and different antioxidants attenuate I/R-induced subcellular alterations and improve the recovery of cardiac function. Thus, we are faced with the task of developing safe and effective antioxidants as well as agents for upregulating the expression of endogenous antioxidants for the therapy of I/R injury. Full article

Background/Objectives: Myocardial infarction (MI) and diabetes pose significant health challenges globally, necessitating the development of innovative medication strategies to improve outcomes in affected populations. This research aimed to determine the defensive impact of ferulic acid (FA) against isoproterenol-induced myocardial infarction (MI) in diabetic rats. Methods: A group of male rats was partitioned into five distinct groups: control group, diabetic group, diabetic + MI, diabetic + MI + 20 mg/kg FA, and diabetic + MI + 40 mg/kg FA. The experimental groups received isoproterenol (ISO) subcutaneously at a dosage of 50 mg/kg body weight for two consecutive days. Results: The outcome was severe cardiac toxicity, as shown by changes in electrocardiogram (ECG) rhythm and a substantial increase in blood cardiac enzymes such as creatinine kinase (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). Additionally, there was a surge in inflammatory cytokines, like tumor necrosis factor-alpha (TNF-α), and a disruption of the antioxidant system, evidenced by a rise in malondialdehyde (MDA) content. Moreover, there was a rise in cardiac receptor of advanced glycation end products (RAGE). Treatment with FA with escalating dosages of 20 and 40 mg/kg b.w. effectively mitigated changes in serum cardiac enzymes and improved the cellular architecture, which was evaluated by histopathological examination. Conclusions: In conclusion, in a dose-dependent manner, FA successfully showed a cardioprotective effect against ISO-induced cardiac toxicity in diabetic rats, as shown by the improvement in ECG findings, normalization of serum cardiac biomarkers, and augmentation of the endogenous antioxidant system. Therefore, the aforementioned data indicate that ferulic acid may potentially have a protective effect on MI patients who have diabetes mellitus. Full article

Cardiac ischemia–reperfusion injury (IRI) occurs when blood flow is restored to the myocardium after a period of ischemia, leading to oxidative stress and subsequent myocardial cell damage, primarily due to the accumulation of reactive oxygen species (ROS). In our previous research, we identified that miR-25 is significantly overexpressed in pressure overload-induced heart failure, and its inhibition improves cardiac function by restoring the expression of SERCA2a, a key protein involved in calcium regulation. In this study, we aimed to investigate the role of miR-25 in the context of ischemia–reperfusion injury. We found that miR-25 was markedly upregulated under hypoxic conditions in both in vitro and in vivo models. Through in silico analysis, we identified Sestrin3 (SESN3), an antioxidant protein known for its protective effects against oxidative stress, as a novel target of miR-25. Based on these findings, we hypothesized that inhibiting miR-25 would restore Sestrin3 expression, thereby reducing ROS-induced myocardial cell damage and improving cardiac function. To test this hypothesis, we employed two model systems: a hypoxia/reoxygenation (H/R) stress model using H9c2 myoblasts and a surgically induced ischemia–reperfusion injury mouse model. Our results demonstrated that the use of miR-25 inhibitors significantly improved cardiac function and reduced myocardial damage in both models through the restoration of SESN3 expression. In conclusion, our findings suggest that targeting miR-25 may serve as a novel therapeutic modality to alleviate oxidative damage in the heart. Full article

Cirrhotic cardiomyopathy (CCM) is a diagnostic entity defined as cardiac dysfunction (diastolic and/or systolic) in patients with liver cirrhosis, in the absence of overt cardiac disorder. Pathogenically, CCM stems from a combination of systemic and local hepatic factors that, through hemodynamic and neurohormonal changes, affect the balance of cardiac function and lead to its remodeling. Vascular changes in cirrhosis, mostly driven by portal hypertension, splanchnic vasodilatation, and increased cardiac output alongside maladaptively upregulated feedback systems, lead to fluid accumulation, venostasis, and cardiac dysfunction. Autocrine and endocrine proinflammatory cytokines (TNF-alpha, IL-6), as well as systemic endotoxemia stemming from impaired intestinal permeability, contribute to myocardial remodeling and fibrosis, which further compromise the contractility and relaxation of the heart. Additionally, relative adrenal insufficiency is often present in cirrhosis, further potentiating cardiac dysfunction, ultimately leading to the development of CCM. Considering its subclinical course, CCM diagnosis remains challenging. It relies mostly on stress echocardiography or advanced imaging techniques such as speckle-tracking echocardiography. Currently, there is no specific treatment for CCM, as it vastly overlaps with the treatment of heart failure. Diuretics play a central role. The role of non-selective beta-blockers in treating portal hypertension is established; however, their role in CCM remains somewhat controversial as their effect on prognosis is unclear. However, our group still advocates them as essential tools in optimizing the neurohumoral pathologic axis that perpetuates CCM. Other targeted therapies with direct anti-inflammatory and antioxidative effects still lack sufficient evidence for wide approval. This is not only a review but also a comprehensive distillation of the insights from practicing clinical hepatologists and other specialties engaged in advanced approaches to treating liver disease and its sequelae. Full article

Background and Objectives: Ischemia-reperfusion (I/R) injury is a process in which impaired perfusion is restored by restoring blood flow and tissue recirculation. Nanomedicine uses cutting-edge technologies that emerge from interdisciplinary influences. In the literature, there are very few in vivo and in vitro studies on how cerium oxide (CeO₂) affects systemic anti-inflammatory response and inflammation. Therefore, in our study, we aimed to investigate whether CeO₂ administration has a protective effect against myocardial I/R injury in the liver and kidneys. Materials and Methods: Twenty-four rats were randomly divided into four groups after obtaining approval from an ethics committee. A control (group C), cerium oxide (group CO), IR (group IR), and Cerium oxide-IR (CO-IR group) groups were formed. Intraperitoneal CeO₂ was administered at a dose of 0.5 mg/kg 30 min before left thoracotomy and left main coronary (LAD) ligation, and myocardial muscle ischemia was induced for 30 min. After LAD ligation was removed, reperfusion was performed for 120 min. All rats were euthanized using ketamine, and blood was collected. Liver and kidney tissue samples were evaluated histopathologically. Serum AST (aspartate aminotransferase), ALT (alanine aminotransaminase), GGT (gamma-glutamyl transferase), glucose, TOS (Total Oxidant Status), and TAS (Total Antioxidant Status) levels were also measured. Results: Necrotic cell and mononuclear cell infiltration in the liver parenchyma of rats in the IR group was observed to be significantly increased compared to the other groups. Hepatocyte degeneration was greater in the IR group compared to groups C and CO. Vascular vacuolization and hypertrophy, tubular degeneration, and necrosis were increased in the kidney tissue of the IR group compared to the other groups. Tubular dilatation was significantly higher in the IR group than in the C and CO groups. TOS was significantly higher in all groups than in the IR group (p < 0.0001, p < 0.0001, and p = 0.006, respectively). However, TAS level was lower in the IR group than in the other groups (p = 0.002, p = 0.020, and p = 0.031, respectively). Renal and liver histopathological findings decreased significantly in the CO-IR group compared to the IR group. A decrease in the TOS level and an increase in the TAS level were found compared to the IR group. The AST, ALT, GGT, and Glucose levels are shown. Conclusions: CeO₂ administered before ischemia-reperfusion reduced oxidative stress and ameliorated IR-induced damage in distant organs. We suggest that CeO₂ exerts protective effects in the myocardial IR model. Full article

In heart failure (HF) patients undergoing cardiac surgery, an increased activity of mechanisms related to cardiac remodeling may determine a higher risk of postoperative atrial fibrillation (POAF). Given that atrial fibrillation (AF) has a negative impact on the course and management of HF, including the need for anticoagulation therapy, identifying the factors associated with AF occurrence after cardiac surgery is crucial for the prognosis of these patients. POAF is thought to occur when various clinical and biochemical triggers act on susceptible cardiac tissue (first hit), with oxidative stress and inflammation during cardiopulmonary bypass (CPB) surgery being potential contributing factors (second hit). However, the molecular mechanisms involved in these processes remain poorly characterized. Recent research has shown that patients who later develop POAF often have pre-existing abnormalities in calcium handling and activation of NLRP3-inflammasome signaling in their atrial cardiomyocytes. These molecular changes may make cardiomyocytes more susceptible to spontaneous Ca2+-releases and subsequent arrhythmias, particularly when exposed to inflammatory mediators. Additionally, some clinical studies have linked POAF with elevated preoperative inflammatory markers, but there is a need for further research in order to better understand the impact of CPB surgery on local and systemic inflammation. This knowledge would make it possible to determine whether patients susceptible to POAF have pre-existing inflammatory conditions or cellular electrophysiological factors that make them more prone to developing AF and cardiac remodeling. In this context, the NLRP3 inflammasome, expressed in cardiomyocytes and cardiac fibroblasts, has been identified as playing a key role in the development of HF and AF, making patients with pre-existing HF with reduced ejection fraction (HFrEF) the focus of several clinical studies with interventions that act at this level. On the other hand, HFpEF has been linked to metabolic and non-ischemic risk factors, but more research is needed to better characterize the myocardial remodeling events associated with HFpEF. Therefore, since ventricular remodeling may differ between HFrEF and HFpEF, it is necessary to perform studies in both groups of patients due to their pathophysiological variations. Clinical evidence has shown that pharmacological therapies that are effective for HFrEF may not provide the same anti-remodeling benefits in HFpEF patients, particularly compared to traditional adrenergic and renin–angiotensin–aldosterone system inhibitors. On the other hand, there is growing interest in medications with pleiotropic or antioxidant/anti-inflammatory effects, such as sodium–glucose cotransporter 2 inhibitors (SGLT-2is). These drugs may offer anti-remodeling effects in both HFrEF and HFpEF by inhibiting pro-inflammatory, pro-oxidant, and NLRP3 signaling pathways and their mediators. The anti-inflammatory, antioxidant, and anti-remodeling effects of SGLT-2 i have progressively expanded from HFrEF and HFpEF to other forms of cardiac remodeling. However, these advances in research have not yet encompassed POAF despite its associations with inflammation, oxidative stress, and remodeling. Currently, the direct or indirect effects of NLRP3-dependent pathway inhibition on the occurrence of POAF have not been clinically assessed. However, given that NLRP3 pathway inhibition may also indirectly affect other pathways, such as inhibition of NF-kappaB or inhibition of matrix synthesis, which are strongly linked to POAF and cardiac remodeling, it is reasonable to hypothesize that this type of intervention could play a role in preventing these events. Full article

Precision medicine is envisioned as the future of cardiovascular healthcare, offering a more tailored and effective method for managing cardiovascular diseases compared to the traditional one-size-fits-all approaches. The complex role of oxidative stress in chronic diseases within the framework of precision medicine was carefully explored, delving into the cellular redox status and its critical involvement in the pathophysiological complexity of cardiovascular diseases (CVDs). The review outlines the mechanisms of reactive oxygen species generation and the function of antioxidants in maintaining redox balance. It emphasizes the elevated reactive oxygen species concentrations observed in heart failure and their detrimental impact on cardiovascular health. Various sources of ROS within the cardiovascular system are examined, including mitochondrial dysfunction, which contributes to oxidative stress and mitochondrial DNA degradation. The article also addresses oxidative stress’s role in myocardial remodeling, a process pivotal to the progression of heart diseases. By integrating these aspects, the review underscores the importance of redox homeostasis and identifies molecular biomarkers that can enhance precision therapy for CVDs. The insights provided aim to pave the way for targeted therapeutic strategies that mitigate oxidative stress, thereby improving patient outcomes in cardiovascular medicine. Full article

Background: The adverse effects of a Western diet on obesity and diabetes among reproductive-aged women pose a significant threat to the cardiovascular health of their offspring. Given the crucial role of glutathione metabolism and glutathione-related antioxidant defense systems in cardiovascular diseases through scavenging ROS and maintaining redox homeostasis, further exploration of their specific influence is imperative to develop therapeutic strategies for cardiomyopathy induced by a maternal Western diet. Methods: We developed a prenatal maternal Western diet exposure model in C57/B6 mice to investigate cardiac morphology and function through histological analysis and echocardiography. RNA sequencing and analysis were utilized to elucidate the mechanisms underlying the impact of a maternal Western diet and N-acetylcysteine treatment on cardiomyopathy. Additionally, ELISAs, transmission electron microscopy, and flow cytometry were employed to assess the antioxidant defense system and mitochondrial ROS levels in progenitor cardiomyocytes. Results: N-acetylcysteine significantly mitigated cardiomyocyte hypertrophy, myocardial interstitial fibrosis, collagen type I accumulation, and left ventricular remodeling induced by a maternal Western diet, particularly in male offspring. Furthermore, N-acetylcysteine reversed the increase in apoptosis and the increase in the β/α-MyHC ratio in the myocardium of offspring that results from a maternal Western diet. RNA sequencing and GSEA revealed that the beneficial effects of N-acetylcysteine were linked to its ability to modulate oxidative phosphorylation pathways. Additionally, N-acetylcysteine treatment during pregnancy can markedly elevate glutathione levels, augment glutathione peroxidase (GPx) activity, and mitigate the accumulation of mitochondrial ROS caused by a maternal Western diet. Conclusions: N-acetylcysteine mitigated cardiomyopathy induced by a maternal Western diet by bolstering glutathione synthesis and enhancing GPx activity, thereby scavenging mitochondrial ROS and modulating oxidative phosphorylation pathways. Full article

Hyperuricemia (HUA) may lead to myocardial cell damage, thereby promoting the occurrence and adverse outcomes of heart diseases. In this review, we discuss the latest clinical research progress, and explore the impact of HUA on myocardial damage-related diseases such as myocardial infarction, arrhythmias, and heart failure. We also combined recent findings from basic research to analyze potential mechanisms linking HUA with myocardial injury. In different pathological models (such as direct action of high uric acid on myocardial cells or combined with myocardial ischemia-reperfusion model), HUA may cause damage by activating the NOD-like receptor protein 3 inflammasome-induced inflammatory response, interfering with cardiac cell energy metabolism, affecting antioxidant defense systems, and stimulating reactive oxygen species production to enhance the oxidative stress response, ultimately resulting in decreased cardiac function. Additionally, we discuss the impact of lowering uric acid intervention therapy and potential safety issues that may arise. However, as the mechanism underlying HUA-induced myocardial injury is poorly defined, further research is warranted to aid in the development novel therapeutic strategies for HUA-related cardiovascular diseases. Full article

Diabetes mellitus (DM) is a chronic endocrine disorder that affects more than 20 million people in the United States. DM-related complications affect multiple organ systems and are a significant cause of morbidity and mortality among people with DM. Of the numerous acute and chronic complications, atherosclerosis due to diabetic dyslipidemia is a condition that can lead to many life-threatening diseases, such as stroke, coronary artery disease, and myocardial infarction. The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway is an emerging antioxidative pathway and a promising target for the treatment of DM and its complications. This review aims to explore the Nrf2 pathway’s role in combating diabetic dyslipidemia. We will explore risk factors for diabetic dyslipidemia at a cellular level and aim to elucidate how the Nrf2 pathway becomes a potential therapeutic target for DM-related atherosclerosis. Full article