Search Results (3,626)

Background: Cancer and cardiovascular disease are the two leading causes of death in Canada. Although treatments have improved tremendously across the years, interventions such as radiotherapy and chemotherapies are known to have negative impacts on cardiovascular health and can lead to death if not treated in time. Using a retrospective approach, we determined factors associated with cancer therapy-related cardiac dysfunction (CTRCD). Methods: Patients followed through a dedicated Cardio-Oncology clinic with comprehensive screening for CTRCD were identified. CTRCD was defined as a drop in left ventricular ejection fraction of at least 10% to a value lower than 53%. We performed multivariable logistic regression to determine factors associated with CTRCD. Results: In total, 2460 patients with cancer were identified from clinical records—919 had breast cancer, 758 had hematologic malignancies, and 783 had other cancer types. Patients with breast cancer and hematologic malignancies were more likely to experience CTRCD, with odds ratios (ORs) of 2.10 (p = 0.059) and 1.96 (p = 0.047), respectively. Anthracycline and trastuzumab use were independently associated with CTRCD, with ORs of 1.98 (p = 0.002) and 3.19 (p < 0.001), respectively. In hematologic malignancy patients, hypertension (OR = 2.18, p = 0.047) and diabetes (OR = 2.31, p = 0.036) were also significant predictors of CTRCD. Conclusions: We confirmed the importance of anthracycline, trastuzumab, and radiation in the development of CTRCD. However, among patients with hematologic malignancies, traditional cardiovascular risk factors are also associated with CTRCD. This information could help physicians personalize CTRCD surveillance strategies. Full article

Mitochondria are central regulators of cardiac homeostasis, integrating energy production, redox balance, calcium handling, and innate immune signaling. In cardiovascular disease (CVD), mitochondrial dysfunction acts as a unifying mechanism connecting oxidative stress, metabolic inflexibility, inflammation, and structural remodeling. Disturbances in mitochondrial quality control—encompassing fusion–fission dynamics, PINK1/Parkin- and receptor-mediated mitophagy, biogenesis, and proteostasis—compromise mitochondrial integrity and amplify cardiomyocyte injury. Excess reactive oxygen species, mitochondrial DNA release, and calcium overload further activate cGAS–STING, NLRP3 inflammasomes, and mPTP-driven cell death pathways, perpetuating maladaptive remodeling. Therapeutic strategies targeting mitochondrial dysfunction have rapidly expanded, ranging from mitochondria-targeted antioxidants (such as MitoQ and SS-31), nutraceuticals, metabolic modulators (SGLT2 inhibitors, metformin), and mitophagy or biogenesis activators to innovative approaches including mtDNA editing, nanocarrier-based delivery, and mitochondrial transplantation. These interventions aim to restore organelle structure, improve bioenergetics, and reestablish balanced quality control networks. This review integrates recent mechanistic insights with emerging translational evidence, outlining how mitochondria function as bioenergetic and inflammatory hubs in CVD. By synthesizing established and next-generation therapeutic strategies, it highlights the potential of precision mitochondrial medicine to reshape the future management of cardiovascular disease. Full article

Erectile dysfunction (ED) is one of the most prevalent and disabling complications of diabetes mellitus (DM), thought to arise from the interaction of metabolic, vascular, and neural injury. Recent evidence indicates that diabetic neuropathy, affecting both somatic and autonomic pathways, plays a central role in the development of ED and is strongly associated with increased disease burden. Early neurophysiological studies documented impaired penile sensory conduction and abnormalities of sacral reflex pathways in diabetic men with ED, while more recent investigations have confirmed the contribution of cardiovascular autonomic neuropathy and small-fibre loss. At the molecular level, oxidative stress, advanced glycation end-product signalling, impaired nitric oxide bioavailability, and reduced neurotrophic support, particularly involving brain-derived neurotrophic factor (BDNF), emerge as key mechanisms linking diabetes to neural and neurovascular dysfunction. Although phosphodiesterase type-5 inhibitors remain first-line therapy, reduced responsiveness in patients with significant neuropathy highlights the importance of recognising the role of neurogenic mechanisms. Overall, the available evidence supports the conceptualisation of diabetic ED as a neurovascular manifestation within the broader spectrum of diabetic neuropathy rather than as a purely vasculogenic disorder. This review integrates historical and contemporary literature addressing the epidemiology, neurophysiology, pathophysiology and therapeutic implications of ED in diabetes, with a specific focus on its neuropathic substrate. These findings support a paradigm shift toward an integrated neurovascular approach to diabetic ED, highlighting the importance of early neuropathy-oriented assessment and paving the way for future regenerative and neuroprotective therapeutic strategies. Full article

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a prevalent global health issue driven by metabolic syndrome, with cardiovascular disease being the leading cause of mortality. This review synthesizes current knowledge on its multifactorial pathogenesis, the impact of sexual dimorphism, and key experimental models. The progression of MASLD involves interconnected pathways including dysregulated de novo lipogenesis, insulin resistance, mitochondrial dysfunction, gut dysbiosis, ferroptosis, and genetic and epigenetic predispositions. These mechanisms not only promote hepatic injury but also accelerate atherosclerosis. Notably, MASLD exhibits significant sexual dimorphism, influenced by physiological differences, sex hormones, genetic factors, and the microbiome. The study of these complex processes relies mostly on dietary-induced animal models, particularly in rats, which effectively recapitulate features of the human disease. Given the multifaceted nature of MASLD, the therapeutic focus is shifting from monotherapies to combination or dual-target strategies. To enable this transition, refinement of preclinical models is essential to better understand and target this complex disorder. Full article

Background: Menopause is accompanied by hormonal alterations that are closely linked to changes in body composition, insulin sensitivity, and cardiovascular risk in women. Gremlin-1 has recently been identified as an adipokine involved in metabolic and reproductive aging; however, its associations with endocrine and lipid biomarkers across the menopausal transition remain incompletely defined. Objectives: To evaluate the relationships between plasma Gremlin-1 and IGF-1, HDL cholesterol, estradiol, and age in reproductive-aged and postmenopausal women. Methods: This cross-sectional study included 88 women aged 18–65 years, stratified by menopausal status (reproductive-aged vs. postmenopausal). Plasma concentrations of Gremlin-1, growth hormone, IGF-1, insulin, estradiol (E2), glucose, HbA1c, and a standard lipid profile were measured. Results: Plasma Gremlin-1 concentrations were significantly higher in postmenopausal women compared with reproductive-aged women (p < 0.001). Age (p = 0.013), but not menopause status (p = 0.874), was associated with Gremlin-1 levels. Gremlin-1 showed a strong inverse association with IGF-1 (p = 0.003) and a negative correlation with HDL cholesterol (p = 0.03) in non-obese women; however this association disappeared after adjustment for age. Conclusion: Circulating Gremlin-1 primarily reflects chronological aging and associated endocrine–metabolic changes rather than menopausal status or adiposity per se. While unadjusted associations with metabolic biomarkers are detectable, these relationships are largely attributable to aging. Gremlin-1 may therefore serve as a marker of systemic aging-related endocrine–metabolic remodeling rather than a specific indicator of ovarian aging or adipose tissue dysfunction. Full article

Mechanosensitive ion channels (MSCs) are fundamental transducers that convert mechanical forces into electrochemical signals, enabling cells to regulate processes such as Ca²⁺ homeostasis, migration, proliferation, and adhesion. Located in both plasma and organellar membranes, MSCs, including Piezos, TRPs, K2Ps, MscL, and MscS families exhibit diverse ion selectivity, gating mechanisms and physiological roles. Emerging evidence demonstrates that lipids are dynamic regulators of MSC activation, sensitivity, and kinetics. Endogenous membrane lipids such as cholesterol, phospholipids, sphingolipids and fatty acids modulate MSC behavior by altering bilayer tension, curvature, stiffness and protein–lipid interactions. Exogenous lipids, including dietary fatty acids and lipid-derived metabolites, influence MSCs by modifying membrane physical properties or engaging specific lipid-binding sites on channel proteins. These interactions shape fundamental biological processes and contribute to disease mechanisms in cardiovascular dysfunction, neurological disorders, metabolic disease, and cancer. Despite significant progress, the molecular principles by which lipids regulate MSC conformational transitions and force sensing remain incompletely defined. This review synthesizes current knowledge on endogenous and exogenous lipid modulation of MSCs, integrating structural, computational and electrophysiological insights to highlight emerging therapeutic opportunities targeting lipid–mechanotransduction interfaces. Full article

Background: The number of patients with chronic coronary syndromes (CCS) is growing, influenced by factors such as increasing life expectancy and prevalence of risk factors. Thus, cardiovascular (CV) disease remains the leading cause of mortality and morbidity worldwide. The main objective of the study was to identify factors associated with long-term survival in patients with chronic coronary syndrome, with a focus on kidney function described by eGFR and albuminuria (assessed by uACR). Methods: The study comprised a total of 257 patients from Bialystok (Poland), aged ≤ 80 years, who 6–18 months earlier were hospitalized for acute coronary syndrome or elective myocardial revascularization. During the 80-month follow-up, 40 (15.6%) patients died, while there was no information about three (1.2%) patients. Patients with preserved eGFR and without albuminuria were characterized by the longest survival, with deterioration of prognosis in groups of progressive kidney dysfunction as defined by KDIGO based on eGFR and uACR. The primary endpoint was death from any cause. Results: Those who survived the 80-month follow-up period were younger (p < 0.001), had a lower waist circumference (p = 0.028), higher diastolic blood pressure (p = 0.026), lower NTproBNP (p < 0.001) and hsCRP (p = 0.001) concentrations, reduced eGFR (p = 0.004) and increased ACR (p = 0.023) were strongly associated with mortality. In logistic regression analysis with stepwise elimination of variables, the strongest factors affecting survival were hemoglobin concentration, left ventricle ejection fraction (LVEF) and hsCRP. Conclusions: Measurement of albuminuria, in addition to eGFR, allows patients to be correctly classified into CV risk categories and facilitates appropriate treatment of patients with CCS. Higher diastolic blood pressure (but still within normal range) was found in patients who later survived 6 years. Measurements of hsCRP, hemoglobin concentration and LVEF help to identify CCS patients at the highest risk of mortality in long-term follow-up. Full article

Atherosclerosis is a progressive cardiovascular disease characterized by lipid accumulation, oxidative stress, and inflammation within the arterial walls. Environmental pollutants, including particulate matter (PM), diesel exhaust particles (DEPs), and heavy metals, contribute directly to the initiation and progression of arterial plaques by promoting LDL oxidation, endothelial dysfunction, foam cell formation, and vascular inflammation, whilst high-density lipoprotein (HDL) provides protective effects. This review examines the mechanistic links between environmental exposures, lipid dysregulation, and plaque formation, highlighting how both gaseous and particulate pollutants and toxic and essential metals, as well as endocrine disrupting chemicals, influence atherosclerotic risk. Potential antioxidant and lifestyle interventions to mitigate these pollutant-driven effects are also discussed. Full article

Obesity is a complex metabolic disorder characterized by excessive accumulation of adipose tissue, resulting from an imbalance between energy intake and expenditure. It is associated with an increased risk of chronic diseases such as type 2 diabetes, cardiovascular disease, and cancer. Kefiran is a water-soluble exopolysaccharide produced by lactic acid bacteria, Lactobacillus kefiranofaciens, in kefir grains, composed primarily of glucose and galactose. It has garnered scientific interest due to its antioxidant, anti-inflammatory, and antimicrobial properties. Rice Kefiran (RK) is a functional food made with culturing L. kefiranofaciens in a medium containing rice. It is standardized to contain at least 5 mg/g of kefiran. This study investigated the anti-obesity effect of RK on a high-fat diet (HFD)-induced obese mouse model. HFD-fed mice exhibited marked increases in body weight gain (10.3 g vs. 2.0 g in controls) and adipose tissue mass (2.4 g vs. 0.4 g in controls). RK administration significantly attenuated weight gain to 8.3 g and 6.0 g at doses of 10 and 50 mg/kg, respectively, and reduced adipose tissue mass to 2.2 g (RK10) and 1.7 g (RK50). Oral glucose tolerance testing revealed impaired glucose clearance in HFD-fed mice, with blood glucose levels of 403.5 mg/dL at 15 min and 314.6 mg/dL at 120 min, compared with 348.8 mg/dL and 232.2 mg/dL in controls. RK treatment improved glucose tolerance, particularly at 50 mg/kg, reducing glucose levels to 359.0 mg/dL at 15 min and 263.8 mg/dL at 120 min. Biochemical analyses demonstrated that RK significantly reduced serum total cholesterol (213.6 mg/dL in HFD vs. 178.0 and 184.0 mg/dL in RK10 and RK50), triglycerides (379.0 mg/dL in HFD vs. 228.8 and 234.6 mg/dL), and non-esterified fatty acids (0.89 mEq/mL in HFD vs. 0.54 and 0.35 mEq/mL), while phospholipid levels remained unchanged. Furthermore, RK increased serum nicotinamide phosphoribosyltransferase (NAMPT) levels from 15.8 ng/mL in HFD-fed mice to 30.0 and 50.0 ng/mL in the RK10 and RK50 groups, respectively, and restored hepatic NAD⁺/NADH ratios toward control levels (1.78 µmol/L in HFD vs. 1.90 µmol/L and 2.07 µmol/L in RK10 and RK50). Gene expression analysis showed that RK increased Nampt mRNA expression and decreased the mRNA expression of adipogenic and lipogenic genes, including Srebp-1c, Acc-1, and Fas. These findings suggest that RK may ameliorate obesity-related metabolic disturbances and its associated metabolic dysfunctions by modulating lipid metabolism, glucose tolerance, and NAD⁺ biosynthesis pathways. Full article

Chronic pain is a multisystem disorder involving neuroimmune activation, metabolic dysregulation, mitochondrial dysfunction, and alterations in autonomic and sensory signaling, leading to peripheral and central sensitization, reduced responsiveness to standard analgesics, and persistent symptoms. Growing evidence suggests that several widely used systemic drugs, initially developed for metabolic, cardiovascular, immunological, or neurological conditions, interact with biological mechanisms involved in pain pathophysiology. This narrative review examines the mechanistic and emerging clinical evidence describing how systemically administered pharmacological agents interact with pathways implicated in chronic pain, focusing on glucagon-like peptide-1 receptor agonists, sodium–glucose cotransporter-2 inhibitors, metformin, statins, minocycline, ibudilast, low-dose naltrexone, beta-blockers, and cannabinoids. The mechanisms reviewed include glial activation, cytokine signaling, oxidative stress, mitochondrial dysfunction, ion channel sensitization, and autonomic imbalance. The use of these systemic agents may provide additional treatment options for patients with chronic neuropathic, centralized, or mixed pain states who have limited response to conventional therapies, although current clinical evidence remains preliminary. Full article

Survival rates for children, adolescents, and young adults (CAYA) with cancer have markedly improved over recent decades, resulting in a rapidly growing population of long-term survivors. However, many of these individuals experience late and long-term treatment-related effects that resemble conditions typically associated with advanced age, including cardiovascular disease, endocrine dysfunction, neurocognitive impairment, and secondary malignancies. This clinical constellation has led to the concept of therapy-induced accelerated aging, suggesting that cancer treatments provoke biological changes that mirror, and may accelerate, physiological aging processes. In this review, we examine current evidence for aging-associated molecular hallmarks in CAYA cancer survivors, focusing on epigenetic alterations, genomic instability, chronic inflammation, cellular senescence, telomere attrition, and mitochondrial dysfunction. Epigenetic age acceleration is consistently observed across multiple survivor cohorts and correlates with treatment exposures, lifestyle factors, and chronic health conditions, positioning DNA methylation-based clocks as promising integrative biomarkers. Likewise, clonal hematopoiesis—reflecting persistent genomic stress—appears enriched in survivors, particularly decades after therapy, and may serve as an indicator of long-term cardiovascular and hematologic risk. Immune dysregulation, inflammaging, and senescence markers further underscore the systemic impact of cancer therapies on biological aging pathways. While telomere shortening and mitochondrial alterations also contribute to this phenotype, their standalone biomarker utility remains limited. Together, these hallmarks highlight the multifaceted nature of accelerated aging in CAYA survivors. Future work integrating multi-omics biomarkers with clinical phenotyping will be essential to identify high-risk individuals, guide targeted interventions, and advance personalized survivorship care. Full article

Vascular inflammation and endothelial dysfunction are key drivers in the development of cardiovascular and neurovascular diseases. Mitochondrial dysfunction and oxidative stress further amplify inflammatory cascades, emphasising the need for targeted strategies that restore endothelial homeostasis at the subcellular level. Hydrogen sulphide (H₂S) donors, such as AP39, offer cytoprotective benefits but are limited by short half-life and rapid release of the active compound, H₂S. We developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating AP39 (PLGA-AP39) to achieve sustained, mitochondria-targeted H₂S delivery. Nanoparticles were characterised by size, polydispersity, zeta potential, encapsulation efficiency, and in vitro release kinetics. Human umbilical vein endothelial cells (HUVEC) were exposed to TNF-α to induce inflammation, followed by treatment with free AP39 or PLGA-AP39. Anti-inflammatory effects were assessed by measuring IL-6, IL-8, and TGF-β levels. Mitochondrial function was evaluated using a Seahorse XFe24 Analyser, membrane potential assays, and mitochondrial ROS detection. Moreover, we investigated vascular function by analysing capillary-like tube formation and wound closure in response to treatments. PLGA-AP39 nanoparticles displayed a uniform size (~227 nm), low PDI, and high encapsulation efficiency (>78%). Sustained AP39 release was observed over seven days. Treatment with PLGA-AP39 significantly restored TNF-α-induced endothelial dysfunction and reduced TNF-α-induced release of IL-6, IL-8, and TGF-β compared to untreated controls. Seahorse analysis revealed restoration of maximal respiration and increased spare respiratory capacity. Encapsulated AP39 also preserved mitochondrial membrane potential and reduced mitochondrial ROS production, demonstrating enhanced protection against inflammation-induced metabolic dysfunction. This work establishes a novel nanoparticle-based strategy for prolonged, mitochondria-specific H₂S delivery to counteract vascular inflammation and enhance endothelial bioenergetics. The results from this work are pioneering in the generation of a novel delivery method for H₂S donors employing PLGA and represent a promising therapeutic avenue for treating chronic vascular inflammatory disorders. Full article

Cardiovascular diseases and metabolic dysfunction-associated steatotic liver disease (MASLD) are increasing sharply worldwide and share overlapping pathophysiological pathways, including oxidative stress, inflammation, hyperglycemia, obesity, dyslipidemia, and hypertension. Dark chocolate, rich in cocoa flavanols such as epicatechin and catechin, exhibits antioxidant and anti-inflammatory effects. Based on these properties, this narrative review uniquely integrates evidence on chocolate’s effects on both cardiovascular and hepatic health, exploring shared mechanisms and clinical implications. Evidence from clinical studies suggests that chocolate modulates nitric oxide bioavailability and NADPH oxidase activity. Clinical findings demonstrate improvements in flow-mediated dilation, decreased NT-proBNP, reduced intestinal permeability and endotoxemia, improved lipid profile (increased HDL-c and reduced total cholesterol, LDL-c, and triglycerides), increased plasma polyphenols, improved platelet function, and attenuated hepatocyte apoptosis. These findings suggest a potential role for cocoa flavanol-rich dark chocolate in cardiometabolic health; however, the evidence remains preliminary and is limited by heterogeneous study designs, small sample sizes, and short intervention durations. Despite these limitations, current evidence supports the inclusion of moderate dark chocolate consumption as a possible adjunct strategy to mitigate cardiometabolic and hepatic metabolic risks. Further large-scale, long-term trials are needed to confirm these beneficial effects and to standardize the dosage and formulation of cocoa flavanols. Full article

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease associated with an increased risk of cardiovascular complications, including heart failure (HF). HF represents a major cause of morbidity and mortality among patients with RA, contributing substantially to their reduced life expectancy. The early detection and optimal management of both traditional cardiovascular risk factors and RA-related inflammation are crucial to improving outcomes. In this comprehensive narrative review, we synthesize and critically appraise contemporary evidence on the epidemiology, pathophysiology, diagnosis, and management of HF in RA. We further explore emerging insights into the inflammatory and immune-mediated mechanisms driving myocardial dysfunction, advances in the early and preclinical detection of HF through novel imaging and biomarker approaches, and the evolving impact of modern RA therapies on cardiovascular health with a focus on heart failure. These developments highlight the importance of integrated, multidisciplinary strategies to prevent and manage heart failure in patients with rheumatoid arthritis. Full article

Despite decades of interventions targeting modifiable risk factors to reduce the burden of cardiovascular disease, ischemic heart disease (IHD) remains the leading cause of mortality and the second leading cause of disability-adjusted life-years worldwide. Growing evidence suggests that phthalates–plasticizers widely used in consumer products, cosmetics, and medical devices, and therefore ubiquitous across environmental media, may contribute to IHD development. Epidemiological studies have reported associations between phthalate exposure and multiple markers of atherosclerosis, the pathological hallmark of IHD, with or without mediation by traditional cardiovascular risk factors. Experimental models support these findings, showing that phthalates can induce oxidative stress, mitochondrial dysfunction, apoptosis, lipid accumulation, and epigenetic alterations, all of which promote endothelial damage and atherogenesis. In this review, we synthesize current epidemiological findings linking phthalate exposure to IHD, describe the main cellular and molecular mechanisms involved, and outline research gaps and regulatory perspectives. We also discuss how novel analytical frameworks—including artificial intelligence—may enhance the integration of environmental, clinical, and molecular data to advance risk prediction and prevention strategies. Full article