Search Results (277)

Dietary bioactive compounds are increasingly explored as complementary cardioprotective strategies, and the nitration of unsaturated fatty acids has emerged as a process capable of enhancing antiplatelet properties. This study investigated whether Phaseolus vulgaris L. extracts can generate nitrated fatty acids under gastric-like conditions and evaluated their effects on human platelet function. Bean extracts and major fatty acids were nitrated in vitro and tested using washed platelets to assess cytotoxicity, TRAP-6 and collagen-induced aggregation, activation markers (P-selectin, CD63), and mitochondrial responses including membrane potential, ROS production, and Ca²⁺ dynamics. Nitrated extracts markedly inhibited TRAP-6 induced aggregation (IC₅₀ ≈ 1.8 mg/mL), whereas non-nitrated extracts showed minimal activity; this effect was reversed by β-mercaptoethanol, indicating dependence on electrophilic nitroalkenes. Fractionation revealed that the lipidic fraction accounted for most of the antiplatelet effect, and isolated nitrated fatty acids (NO₂-LN, NO₂-LA, NO₂-OA) displayed stronger inhibition than their native counterparts without increasing cytotoxicity. Nitrated species additionally reduced mitochondrial membrane potential and granule secretion without elevating ROS. These findings identify Phaseolus vulgaris L. as a natural source of bioactive nitrated fatty acids and support their potential as nutraceutical agents capable of modulating platelet activation and contributing to cardiovascular risk reduction. Full article

Background/Objectives: Doxorubicin (DOX) is an effective chemotherapeutic agent whose clinical utility is limited by cardiotoxicity. To investigate underlying mechanisms, we employed a multi-omics approach integrating transcriptomics and proteomics, leveraging established mouse models of chronic DOX-induced cardiotoxicity. Methods: Five-week-old male mice received weekly DOX (4 mg/kg) or saline injections for six weeks, with heart tissues harvested 4 days post-treatment. Differentially expressed genes (DEGs) and proteins (DEPs) were identified by bulk RNA-seq and proteomics, validated via qPCR and Western blot, respectively. Key DEPs were validated in plasma samples from DOX-treated breast cancer patients. Additionally, temporal comparison was conducted between DEPs in the mice hearts 4 days and 6 weeks post-DOX. Results: RNA-seq revealed upregulation of stress-responsive genes (Phlda3, Trp53inp1) and circadian regulators (Nr1d1), with downregulation of Apelin and Cd74. Proteomics identified upregulation of serpina3n, thrombospondin-1, and epoxide hydrolase 1. Plasma SERPINA3 concentrations were significantly elevated in breast cancer patients 24 h post-DOX. Gene set enrichment analysis (GSEA) revealed upregulated pathways, including p53 signaling, apoptosis, and unfolded protein response. Integrated omics analysis revealed 2089 gene–protein pairs. GSEA of concordant gene–protein pairs implicated p53 signaling, apoptosis, and epithelial–mesenchymal transition in upregulated pathways, while oxidative phosphorylation and metabolic pathways were downregulated. Temporal comparison with a delayed timepoint (6 weeks post-DOX) uncovered dynamic remodeling of cardiac signaling, with early response dominated by inflammatory and apoptotic responses, and delayed response marked by cell cycle and DNA repair pathway activation. Conclusions: This integrated omics study reveals key molecular pathways and temporal changes in DOX-induced cardiotoxicity, identifying potential biomarkers for future cardioprotective strategies. Full article

Dietary bioactive compounds derived from plant-based and fermented foods act as plei-otropic modulators of human health, exerting antioxidant, anti-inflammatory, cardiopro-tective, neuroprotective, and metabolic effects beyond basic nutrition. Whole foods (fruits, vegetables, grains, nuts) provide synergistic mixtures of bioactives, whereas fermented foods generate a wide range of microbial-derived metabolites (peptides, organic acids) as well as probiotics that enhance nutrient bioavailability and support gut health. The gut microbiota plays a central mediating role in the biological effects of dietary bioactives through a dynamic, bidirectional interaction: dietary compounds shape microbial composition by promoting beneficial taxa and suppressing pathogens, while microbial metabolism converts these compounds into bioactive metabolites, including short-chain fatty acids, that profoundly influence host health. Despite their demonstrated health potential, the clinical translation of many dietary bioactives is limited by low bioavailability, which is influenced by digestion processes, food matrix and processing conditions, host genetics, and individual microbiota profile. Overcoming these limitations requires a deeper understanding of the synergistic interactions among dietary bioactives, probiotics, microbial metabolites, and host signaling pathways. This review provides an integrated perspective of the sources, mechanisms of action, and health effects of food-derived bioactive compounds and probiotic mediated effects, while highlighting current translational challenges and future directions for the development of effective functional foods and personalized nutrition strategies. Full article

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, with growing evidence indicating that epigenetic mechanisms play a central role in their onset and progression. This review provides a comprehensive overview of current knowledge on the epigenetic regulation and molecular mechanisms involved in CVDs, as well as their potential therapeutic implications. The findings demonstrate that DNA methylation, histone modifications, and non-coding RNAs are key regulators of gene expression associated with cardiac hypertrophy, atherosclerosis, myocardial infarction, and heart failure. Interactions between epigenetic alterations and inflammatory or oxidative stress pathways further contribute to endothelial dysfunction and vascular remodeling. Emerging therapeutic strategies targeting these mechanisms, including histone deacetylase inhibitors, DNA methyltransferase inhibitors, and RNA-based therapeutics, show promising cardioprotective effects in experimental and early clinical studies. Overall, this review underscores the significance of epigenetic regulation in cardiovascular pathophysiology and highlights the potential of epigenetic-based interventions as a foundation for precision medicine and novel therapeutic approaches in cardiology. Full article

Cardiovascular diseases (CVDs) have emerged as a common health problem. However, despite their prevalence, little progress has been made in their treatment. In recent years, neurotrophic factors (NTFs) have been discovered to exert cardioprotective functions for CVDs. NTFs can modulate vascular integrity, myocardial remodeling, angiogenesis, and autonomic regulation, playing the roles of maintaining cardiovascular homeostasis and influencing disease progression. Under pathological conditions, the supplement of NTFs can induce substantial adaptations to mitigate adverse cardiac responses. Several NTFs have been investigated in this regard. This review briefly elaborates on present insights into the expression, signaling pathways, and regulatory effects of NTFs on the development of CVDs, and also discusses emerging therapeutic strategies based on NTFs, ranging from exercise to advanced modalities including stem cell therapy, gene transfer, recombinant protein therapy and NTF mimetics, among which the mimetics and exercise interventions emerge as the most promising avenues for clinical translation. Full article

Background/Objectives: Numerous studies have documented cardioprotective effects of adiponectin in animal models of cardiometabolic disease (CMD). Adiponectin receptor agonist ALY688 has demonstrated functional significance against pressure overload-induced cardiac remodeling events in a mouse model of heart failure with reduced ejection fraction (HFrEF), potentially through modulation of the systemic metabolome. However, the specific metabolites and their pathophysiological contribution to cardioprotection in cardiac hypertrophy or heart failure remain unclear. This study aimed to characterize systemic metabolic alterations across five tissues in HFrEF and determine how ALY688 modifies these pathways to mediate cardioprotection in the transverse aortic constriction (TAC) model. Methods: Targeted metabolic profiling was performed on heart, liver, muscle, epididymal white adipose tissue (eWAT), and serum collected five weeks post-surgery from wild-type male C57BL/6 mice. Mice underwent either Sham or TAC-induced left ventricular pressure overload, with or without daily subcutaneous ALY688 administration. Metabolites were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and statistically analyzed at the tissue level. Results: Consistent with pathological cardiac remodeling, the comprehensive metabolomic analysis revealed that TAC induced widespread disruption of systemic metabolic homeostasis. ALY688 treatment significantly modified several key metabolite classes, including triglycerides (TGs) and glycosylceramides (HexCer). Notably, ALY688 also altered multiple gut-derived metabolites, including trimethylamine N-oxide (TMAO), 5-aminovaleric acid (5-AVA), and glycodeoxycholic acid (GDCA), highlighting a potential gut–liver–heart axis mediating its cardioprotective effects. Conclusions: These findings demonstrate that ALY688 mitigates TAC-induced metabolic dysregulation across multiple tissues. The identified metabolic signatures suggest that ALY688 exerts cardioprotective effects, at least in part, through restoration of systemic metabolic homeostasis and engagement of a gut–liver–heart metabolic axis. These results provide mechanistic insight into adiponectin receptor agonism and support further exploration of ALY688 as a potential therapeutic strategy for HFrEF. Full article

Background: Immune checkpoint inhibitors (ICIs) are a new anti-cancer therapy that have improved survival rates in many aggressive cancers. However, while rare, a significant number of patients develop ICI-induced cardiotoxicity. Clinical manifestations are non-specific and underlying cellular mechanisms remain unknown, making diagnosis and treatment of these ICI-induced cardiac side effects difficult. Exercise has shown protective effects against chemotherapy-induced cardiotoxicity but has not been investigated in combination with ICIs. High-intensity exercise has shown greatest cardioprotective effects in preclinical (animal) models, but human cancer patients prefer low-intensity exercise in the clinical setting. Therefore, the purpose of this study was to further identify the cardioprotective effects of low-intensity exercise as a treatment strategy against ICI-induced cardiotoxicity. Methods: Female mice were randomly selected and separated into four groups: sedentary (SED), sedentary ICI-treated (SED + ICI), low-intensity treadmill-exercised (TM), and low-intensity treadmill-exercised ICI-treated mice (TM + ICI). Mice either underwent a 4-week low-intensity treadmill exercise protocol (TM) or remained sedentary (SED). During the 4 weeks, ICI mice received anti-PD-1 treatment (200 μg/mouse) via intraperitoneal injections twice each week. Echocardiography was performed at baseline and sacrifice to determine changes in cardiac structure and function. At sacrifice, cardiac tissue was collected, weighed, and frozen for further biochemical analysis. Underlying metabolic signaling pathways were assessed via Western Blot, and autophagic flux was analyzed via fluorescent microscopy. Results: Echocardiography at sacrifice revealed significantly decreased fractional shortening as a measure of cardiac function (−20%), 1.5-fold dilation of the left ventricle, and thinning of the posterior cardiac wall at systole and diastole in SED + ICI mice compared to SED controls (p < 0.05), indicative of a phenotype of ICI-induced dilated cardiomyopathy. TM + ICI mice did not show a significant difference in these cardiac structural and functional parameters, suggesting cardioprotective effects of low-intensity exercise. In line with these findings, Western Blot and fluorescent microscopy analyses revealed upregulation of autophagic flux (p < 0.05), as well as dysfunctional metabolic pathways (p < 0.05) in ICI-treated mice compared to non-ICI controls. Low-intensity exercise was associated with regulation of dysfunctional metabolism and autophagy in TM + ICI compared to SED + ICI mice. Conclusions: The clinically relevant ICI treatment protocol used in this study led to significant cardiac dysfunction and remodeling, accompanied by underlying dysfunctional metabolism and autophagy. Low-intensity exercise was capable of regulating abnormal protein synthesis and degradation and protecting against ICI-induced cardiotoxicity. This study adds knowledge to the characterization of still unclear clinical manifestations of ICI-induced cardiotoxicity, underlying signaling pathways that could shed light on potential pharmacological treatment targets, as well as the protective effects of low-intensity exercise as a non-pharmacological treatment strategy. Full article

Background: Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and are strongly influenced by dietary habits. Beyond caloric intake, nutrients act as molecular signals that regulate cardiac metabolism, mitochondrial function, inflammation, and epigenetic remodeling. Objectives: This review aims to synthesize current evidence on how dietary patterns and specific nutritional interventions regulate cardiac metabolism and function through interconnected molecular and epigenetic mechanisms, highlighting their relevance for cardiovascular disease prevention. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science, focusing on studies published between 2006 and 2025. Experimental, translational, and clinical studies addressing diet-induced modulation of cardiac metabolic pathways, oxidative and inflammatory signaling, epigenetic regulation, and gut microbiota-derived metabolites were included. Results: The analyzed literature consistently shows that unbalanced diets rich in saturated fats and refined carbohydrates impair cardiac metabolic flexibility by disrupting key nutrient-sensing pathways, including AMP-activated protein kinase (AMPK), proliferator-activated receptor alpha (PPARα), mammalian target of rapamycin (mTOR), and sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1/PGC-1α), leading to mitochondrial dysfunction, oxidative stress, chronic inflammation, and maladaptive remodeling. In contrast, cardioprotective dietary patterns, such as caloric restriction (CR), intermittent fasting (IF), and Mediterranean and plant-based diets, enhance mitochondrial efficiency, redox balance, and metabolic adaptability. These effects are mediated by coordinated activation of AMPK-SIRT1 signaling, suppression of mTOR over-activation, modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, and favorable epigenetic remodeling involving DNA methylation, histone modifications, and non-coding RNAs. Emerging evidence also highlights the central role of gut microbiota-derived metabolites, particularly short-chain fatty acids, in linking diet to epigenetic and metabolic regulation of cardiac function. Conclusions: Diet quality emerges as a key determinant of cardiac metabolic health, acting through integrated molecular, epigenetic, and microbiota-mediated mechanisms. Targeted nutritional strategies can induce long-lasting cardioprotective metabolic and epigenetic adaptations, supporting the concept of diet as a modifiable molecular intervention. These findings provide a mechanistic rationale for integrating personalized nutrition into cardiovascular prevention and precision cardiology, complementing standard pharmacological therapies. Full article

Background: Arterial hypertension (AH) remains a global health concern due to its multifactorial etiology, limited therapeutic success, and high cardiovascular risk. In this context, plant-derived compounds such as essential oils have gained attention as alternative strategies. The monoterpene (-)-linalool (LIN) demonstrates antihypertensive effects. However, its clinical application is hampered by poor solubility and low bioavailability. Methods: This study aimed to investigate the chronic cardiovascular effects of free LIN and its inclusion complex with β-cyclodextrin (LIN/β-CD) in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. Results: Pharmacokinetic analysis showed that complexation with β-CD markedly improved LIN plasma exposure, increasing systemic bioavailability by approximately 20-fold and prolonging its circulation time. In acute assays, intravenous LIN and LIN/β-CD (50 mg/kg) reduced blood pressure in SHR, LIN induced bradycardia, and LIN/β-CD elicited a mild, non-significant tachycardia. Orally administered LIN/β-CD exerted superior antihypertensive effects compared to free LIN. In a 60-day chronic regimen, LIN/β-CD consistently maintained reduced arterial pressure, achieving levels comparable to normotensive controls, while free LIN produced transient effects. LIN/β-CD also significantly reduced the cardiac mass index in SHR, suggesting attenuation of hypertrophic remodeling. Vascular reactivity assays revealed enhanced endothelium-dependent and -independent relaxation and diminished vasoconstriction in LIN/β-CD-treated animals, indicating improved endothelial and smooth muscle function. Histological analyses confirmed the absence of cardiac or vascular injury in both treatment groups. Conclusions: In conclusion, the LIN/β-CD complex improves the pharmacokinetic profile and enhances the arterial morphology, antihypertensive and cardioprotective effects of linalool. These findings support its translational potential as a safe and effective oral formulation for the long-term management of hypertension and associated cardiovascular dysfunction. Full article

Background: Drug-induced cardiotoxicity is a primary concern in clinical practice, especially in the context of oxidative stress induced by anti-cancer, antiviral, and antidiabetic drugs. Several strategies are devised to limit cardiotoxicity, which are supportive and provide symptomatic relief. This highlights the need to develop cardioprotective agents that circumvent the oxidative stress. Bassia indica is a cardiotonic plant with antioxidant properties traditionally used in Africa, South Asia, and China. We investigated its cardioprotective effects against doxorubicin-induced cardiotoxicity (DIC). Methods: B. indica extract (BiE) was analyzed by GC-MS and HPLC. Several antioxidant assays, including DPPH, FRAP, CUPRAC, NO, and H₂O₂ scavenging, were performed. In vivo attenuation of DIC was assessed in a rat model. Results: BiE contained several bioactive flavonoids, including 2-methoxy-4-vinylphenol, ferulic acid, gallic acid, kaempferol, and coumaric acid. Antioxidant assays demonstrated potent free-radical scavenging and antioxidant activity of BiE, providing mechanistic evidence for its in vivo amelioration of DIC. BiE treatment reduced myocardial oxidative stress by increasing endogenous antioxidant levels (p < 0.01), including SOD, CAT, and GSH. It upregulated Nrf2 and lowered Keap1 levels. This was also reflected in the restoration of cardiac tissue architecture and modulation of inflammatory markers, including IL-1β and TNF-α (p < 0.01). Cardiac tissue biomarkers were also improved. Conclusions: These findings conclude that BiE exerts cardiac protection by reducing oxidative stress and inflammation through modulation of the Keap1/Nrf2 pathway and decreasing the expression of IL-1β and TNF-α. Full article

The growing number of cancer cases highlights the urgent need to develop new therapies based on effective molecules. Although anticancer activity remains a key element of oncological pharmacology, the importance of agents that support physiological functions and improve the quality of life of cancer patients is also recognised. Compounds that combine these two functions could represent a significant trend in oncology. Moreover, repurposing approved drugs for conditions beyond their original indications could be a promising strategy. An interesting example of this is synthetic flozins (SGLT2 inhibitors), which were originally designed and developed to treat type 2 diabetes mellitus. These compounds contain various aromatic and heteroaryl structures, and changes in these substituents affect the binding strength and therapeutic potency of SGLT2 inhibitors. Beyond their antidiabetic effects, SGLT2 inhibitors exert well-documented cardioprotective and nephroprotective actions, restoring metabolic homeostasis. Given these pleiotropic properties, they could benefit oncology by improving systemic functions and by directly influencing the invasion of cancer cells. This article provides an overview of the use of synthetic flozins in various contexts, with a particular focus on their potential impact on cancer biology and treatment, consolidating their position as multifunctional agents of growing systemic relevance. Full article

Despite the clinical efficacy of doxorubicin (DOX), effective strategies to prevent its cardiotoxicity are still lacking. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), has demonstrated cardioprotective properties; however, its role and mechanism in DOX-induced cardiotoxicity (DIC) remain unclear. In this study, Finerenone treatment was found to significantly alleviate DOX-induced cardiac dysfunction and pathological remodeling in both mouse models and cultured cells. Mechanistically, molecular docking suggests that Finerenone may directly bind to Latent Transforming Growth Factor Beta Binding Protein 2 (LTBP2), a key regulator of TGF-β bioavailability. This potential binding could inhibit the LTBP2–TGF-β axis, thereby suppressing DOX-induced activation and subsequent Smad3 phosphorylation. The importance of this pathway was supported by the similar anti-fibrotic effects observed with the TGF-β inhibitor LY2109761. However, our findings on the direct binding of Finerenone to LTBP2 are preliminary and require further validation through additional experimental approaches. These results identify LTBP2 as a novel direct target of Finerenone and reveal an additional mechanism underlying its cardioprotective action, suggesting its potential repurposing for the prevention of DIC. Full article

Cardioprotection refers to the natural capacity of heart tissue to resist damage under conditions such as ischemia–reperfusion and various metabolic stresses. First identified in the phenomenon of ischemic preconditioning, the concept has since broadened to encompass other triggers of protective signaling, including hypoxia, temperature shifts, and a wide range of pharmacological compounds. This expansion indicates the presence of common molecular pathways and defense mechanisms. Known intracellular contributors to cardioprotection involve numerous factors, such as protein kinases, the reperfusion injury salvage kinase (RISK) cascade, the Survivor Activating Factor Enhancement (SAFE) pathway, hypoxia-inducible factor-1α (HIF1α), microRNAs, and Connexin 43, among others. These components are crucial in initiating downstream signaling, promoting the expression of protective genes, optimizing mitochondrial function, and regulating cytosolic and protein processes to maintain cardiac resilience. Key end-effectors include SUR2A, a regulatory subunit of sarcolemmal ATP-sensitive potassium (KATP) channels, autophagy, and mitochondria. Central mechanisms, such as modulation of the mitochondrial permeability transition pore and activation of KATP channels, play essential roles in the cardioprotective response. Although significant progress has been made in mapping these networks, many facets remain poorly understood. One of the most pressing challenges is to translate this knowledge into practical therapies and eventually create clinically applicable strategies to protect the heart. Full article

Atherosclerosis is a chronic inflammatory cardiovascular disease that may result from the interaction between oxidative stress, immune dysregulation, and metabolic disorders. Recent studies indicate that the well-known phenolic compounds, hydroxytyrosol (HTyr) and tyrosol (Tyr) present in extra virgin olive oil, confer cardioprotection through various mechanisms of action that include antioxidant, anti-inflammatory, and metabolic regulatory properties. The gut microbiota modulates the structure, bioavailability, and bioactivity of these phenolic compounds, thereby influencing their therapeutic potential. This review explores the intricate interactions between Tyr, HTyr, and gut microbiota within the context of atherosclerosis prevention and management. We explore how gut microbial metabolism can magnify or alter the biological effects of the Tyr and HTyr, and how interindividual differences in microbiota composition may influence their efficacy. A deeper understanding of these mechanisms could support the development of precision nutrition strategies aimed at reducing the risk of atherosclerosis. Full article

Heart failure (HF) is increasing in prevalence in many countries around the world. HF is a complex clinical syndrome characterized by the heart’s inability to pump blood effectively, resulting in significant morbidity and mortality. After an initial cardiac event (e.g., myocardial infarction, valve dysfunction, hypertension, etc.), adaptive mechanisms are activated to preserve cardiac function. Sustained activation of these mechanisms leads to cellular and structural changes involving cardiac remodeling and hypertrophy. This ultimately leads to impaired cardiac contractility and reduced cardiac output, with a 5-year HF-associated mortality rate up to 75%. The current treatment strategies for HF are not sufficient to cover all the underlying complex mechanisms. It has been demonstrated that molecular hydrogen (H₂) exerts cardioprotective effects via its antioxidant, anti-inflammatory, and anti-apoptotic action. The number of studies exploring beneficial effects of H₂ in different HF models is increasing. This is the first review summarizing the knowledge in this field. The available literature indicates that H₂ may be effective in mitigating different HF pathologies via regulating cardiac oxidative stress and inflammation, cardiomyocyte death, and mitochondrial function/cell metabolism, as well as cardiac remodeling, including hypertrophy and fibrosis. As this area of research is still in its infancy, the feasibility and efficiency of H₂ treatment in different HF types need further investigation. Full article