Search Results (5,794)

There has been an immense concern in the healthcare industry about the globally raising rate of cardiovascular disease (CVD). As per recent WHO reports, CVD is the leading cause of disability, hospitalization and premature death. Studies indicate that oxidative stress negatively impacts the heart and vascular system, which could potentially lead to myocardial infarction, hypertension, cardiomyopathies, atherosclerosis and diabetic heart failure, highlighting its significance as a prognostic indicator in cardiovascular conditions. Nowadays, many common experimental assays are used for in-vitro and in-vivo evaluation of oxidative stress and its negative effects on the cardiovascular system. This review aims to serve as a comprehensive guide for researchers seeking to evaluate the impact of oxidative stress on DNA damage in CVD utilizing standardized methods published by leading institutions. To achieve this, we analyzed 208 relevant articles from prominent databases such as Scopus, PubMed, ScienceDirect, etc., summarizing experimental validation of oxidative stress measurements from 1955 to the present. Oxidative stress-induced DNA damage is a key driver of cardiovascular disease progression, yet experimental approaches to study it remains highly variable. This review systematically summarizes established in-vitro and in-vivo models, oxidative stress inducers, and analytical assays used in cardiovascular research. By integrating mechanistic insights with standardized methodologies, it provides a practical framework to guide model selection, improve reproducibility, and enhance translational relevance. This work serves as a concise reference for researchers investigating redox biology, cardiovascular pathology, and antioxidant-based therapeutic strategies. Full article

Non-glycosylated liver-derived acute-phase amyloid A1 and A2 proteins (SAA1 and SAA2, 104 amino acids), generated by two different genes in humans (SAA1/2) and other mammalian species, are considered the prime acute-phase reactants following inflammatory conditions during host defense in cells, tissues, and the circulation. While human SAA3 has been identified as a pseudogene, Saa3 genes in other mammalian species are coding for primarily extrahepatically expressed Saa3 proteins that also may act as suitable inflammatory markers. The discovery of SAA4 (112 amino acids, carrying an octapeptide insert) in humans and mice has paved a new avenue for the exploration of different functions of this so far unknown member of the SAA superfamily. SAA4 has originally been termed a “constitutively” expressed SAA protein, apparently due to its nature not to act as an inflammatory marker. The present overview aimed to cover possible functions—so far identified—for human SAA4 (following its expression in various diseases on mRNA and protein level) and to work out whether SAA4 might be considered—at least in part—an acute-phase protein. Alternatively, we are raising the question whether SAA4 may solely act as a bystander or even underdog within the whole SAA family, where SAA1 and SAA2 proteins (commonly termed acute-phase SAA) hold undoubtedly an eminent status during inflammatory conditions, not only as host defense reactants but also as long-lasting markers for chronic diseases and malignancies in humans. Full article

Background/Objectives: In the last decade, the prevalence of metabolic-associated fatty liver disease (17–46%) and non-alcoholic fatty pancreas disease (NAFPD) (16–33%) has increased due to their association with obesity, both predictors of early atherosclerosis and metabolic risk. Computed tomography (CT) has been proposed as a diagnostic method. Currently, the factors associated with NAFPD have not been fully described. The aim of this study is to describe the prevalence and association of NAFPD and liver steatosis in patients with very high cardiovascular risk. Methods: A retrospective evaluation was conducted on the medical records of patients classified as very high cardiovascular risk who had undergone a CT scan. NAFPD was determined by the difference in pancreatic and splenic attenuation (−1.9), while liver steatosis was identified by hepatic attenuation <40. Bivariate and multivariate analyses were performed to determine the independent factors associated with NAFPD. Results: 169 medical records were collected; 68.6% (n = 116) were men, with a median age of 70 [IQR 61–78] years and 25.8 [IQR 23.7–28.7] kg/m² of body mass index. According to the CT scans, 80.5% (n = 136) presented NAFPD, 24.3% (n = 41) had liver steatosis, and 21.3% (n = 36) had both. In the multivariate analysis, liver steatosis, abnormal levels of aspartate aminotransferase, and being overweight were independent factors associated with NAFPD. Conclusions: In a very high cardiovascular-risk population, the prevalence of NAFPD is high, and it is independently associated with the presence of liver steatosis. Full article

A high-fat, high-cholesterol diet (HFHCD) has a lipotoxic effect on the heart. It not only leads to the development of atherosclerosis but also influences the extracellular matrix within the heart. The aim of the study was to investigate the effect of HFHCD on matrix metalloproteinases MMP-2, MMP-9, MMP-13, and MMP-14 expression in both the cardiac tissue and plasma of ApoE (-/-) mice and on mRNA expression of c-Jun and TGF-β in the cardiac tissue of both ApoE (-/-) mice and wild-type C57BL/6J mice. The study was carried out on two groups of ApoE (-/-) mice: (1) mice from 10 weeks of age that were kept on a HFHCD (n = 10) for the following 14 weeks; (2) control mice (NFD, n = 10) that were kept on a standard, normal-fat diet for the same time as the HFHCD. Additionally, 10 wild-type (WT) mice on a standard, normal-fat diet were also included in the study for mRNA analysis of c-Jun and TGF-β. Atherosclerotic plaque, intima, and media dimensions were assessed in the aortas of the ApoE (-/-) mice by histopathology. Concentrations of MMP-2, MMP-9, MMP-13, and MMP-14 were assessed by ELISA both in cardiac tissue and in the plasma of the ApoE (-/-) HFHCD and ApoE (-/-) NFD mice, while the mRNA expression of c-Jun and TGF-β was assessed by RT-PCR in both the ApoE (-/-) and WT groups. The results demonstrate a significantly increased MMP-9 concentration in the cardiac tissue of the HFHCD mice compared to the NFD mice (2.83 ng/mL vs. 1.91 ng/mL, p = 0.006), and a moderate correlation between the cardiac and plasmatic MMP-9 in ApoE (-/-) mice (r = 0.492, p = 0.0398). Moreover, although the mRNA expression of c-Jun and TGF-β did not differ between NFD and HFHCD ApoE (-/-) mice, the c-Jun expression was significantly elevated in the WT group compared with both ApoE (-/-) groups. The study demonstrated that a high-fat, high-cholesterol diet increases MMP-9 concentration in cardiac tissue, which might reflect its influence on the extracellular matrix within the heart. Full article

Smooth muscle (SM) dysfunction contributes to several pathological conditions, including atherosclerosis; current treatment strategies often fail to restore functional contractility. Adipose-derived stem cells (ADSCs) offer a promising cell source for regenerative medicine due to their accessibility and multipotency. Their differentiation into smooth muscle cells (SMC) is commonly driven by biochemical cues such as retinoic acid and transforming growth factor β; however, supporting this process with additional, non-invasive stimuli may enhance outcomes. Photobiomodulation (PBM) has emerged as a potential modulator of cellular metabolism, mitochondrial function and lineage commitment; however, its role in ADSCs to SMC differentiation remains insufficiently defined. ADSCs were irradiated with green (525 nm), near-infrared (825 nm) or dual wavelengths at 5 J/cm² and 10 J/cm² alongside the growth factors. Proliferation, cytotoxicity, mitochondrial membrane potential, collagen production, migration and smooth muscle marker expression were assessed. PBM induced a fluence-dependent biphasic response. 5 J/cm² fluences enhanced proliferation, mitochondrial activity, collagen deposition and organized SMC marker expression, whereas 10 J/cm² fluences lowered proliferation and membrane potential, reduced collagen and increased migration. PBM at 5 J/cm², especially greenlight, most effectively promoted ADSCs’ progression towards a SMC-like phenotype, with features consistent with a more contractile-like state. Full article

Cardiovascular disease represents the primary cause of morbidity and mortality among patients with chronic kidney disease (CKD). Emerging evidence suggests that coronary artery pathology in CKD diverges from the traditional atherosclerotic phenotype seen in individuals with maintained renal function. This review delineates coronary artery-specific alterations in CKD, focusing on mechanisms that expedite atherogenesis, characteristics of plaques, calcific remodeling, and dysfunction of the coronary microvasculature. CKD fosters a pro-inflammatory, pro-oxidative, and pro-calcific environment, which results in endothelial damage and vascular calcification remodeling. Furthermore, coronary plaques in CKD are more likely to exhibit larger lipid-rich necrotic cores, heightened inflammatory cell infiltration, a significant calcific burden, and vulnerability indicators such as cholesterol crystals and microdisruptions. Impaired coronary microvascular function is also prevalent and may account for ischemia with non-obstructive coronary arteries. In summary, CKD is linked to a rapid, calcification- and inflammation-driven form of coronary disease characterized by both macrovascular plaque remodeling and microvascular dysfunction. This underscores the necessity of early identification and prevention of cardiovascular risk, targeting CKD-specific mechanisms in conjunction with conventional risk factors. Full article

Landmark epidemiological studies and clinical trials, such as the Seven Countries Study, the Lyon Diet Heart Study, the PREDIMED Study and the CORDIOPREV Study, have shown significant reductions in cardiovascular events in those following the Mediterranean diet (MD). The aim of the present work is to summarize the most robust available evidence and the major biological pathways underlying the protective effects of the MD, with particular emphasis on the role of PAF inhibitors. Mechanistically, MD functions through a complex synergy of antioxidant, anti-inflammatory, and antithrombotic effects that collectively improve lipid profiles, enhance endothelial function, optimize postprandial metabolism and cell membrane signaling, making it a functional model for human longevity. The PAF-Implicated Atherosclerosis Theory has emerged as a key unifying framework, proposing that Platelet-Activating Factor (PAF)—a highly potent lipid inflammatory mediator—plays a central role in the initiation and progression of atherosclerosis. Oxidized LDL promotes the production of PAF and PAF-like lipids, leading to endothelial dysfunction, vascular inflammation, and atherosclerotic plaque formation. Traditional Mediterranean foods are rich in natural PAF inhibitors, particularly the polar lipid fractions of extra virgin olive oil, as well as wine, fish, vegetables, onions, and garlic. Animal studies demonstrate that these compounds can reduce or even regress atherosclerotic lesions, independently of serum cholesterol levels. Human dietary interventions have further shown that MD-based meals and functional foods enriched with PAF inhibitors reduce PAF activity and improve thrombosis-related biomarkers. This mechanistic framework helps explain phenomena such as the “French Paradox” and the cardio-protective effects associated with fish consumption. Moreover, the extraction of PAF inhibitors from Mediterranean food by-products, such as olive pomace, offers promising ecological and economic advantages. Collectively, targeting PAF and increasing dietary intake of PAF inhibitors represent promising strategies for the prevention and management of atherosclerosis and other inflammatory diseases, supporting the view that PAF may function as a major, modifiable risk factor in these conditions. Full article

Clonal hematopoiesis refers to the clonal expansion of hematopoietic stem and progenitor cells, driven by somatic mutations. Major mutated genes in clonal hematopoiesis include genes involved in epigenetic regulation including DNA methylation and/or chromatin modification (e.g., DNMT3A, TET2, and ASXL1), tumor suppressors (e.g., TP53), signal transduction (e.g., JAK2), and RNA splicing (e.g., SF3B1 and SRSF2). Clonal hematopoiesis includes clonal hematopoiesis of indeterminate potential (CHIP), clonal cytopenia of unknown significance (CCUS), and myelodysplastic syndromes/neoplasms (MDS). CHIP occurs when the frequency of the variant allele equals or exceeds 2% (4% for X-linked genes in males) in the absence of cytopenias. CHIP is common among older persons and is associated with an increased risk of hematologic cancer. CHIP is also associated with an increased risk of atherosclerotic disease including acute myocardial infarction, stroke, cardiac failure, and abdominal aneurysm. Increasing evidence suggests that CHIP is associated with venous thromboembolic disease. Somatic mutations lead to proliferation of hematopoietic progenitor cells and their progeny, resulting in excessive activation of granulocytes and monocytes. It could be postulated that chronic inflammation caused by clonal expansion of myeloid cells carrying mutations in DNMT3A, TET2, and ASXL1 (“DTA”) genes may constitute an independent risk factor in clot formation and endothelial-cell damage. DTA mutations correlate with elevated proinflammatory cytokines such as IL-1β and IL-6 and enhanced activation of inflammasomes. Moreover, JAK2 mutations may have a direct role in the activation of platelets and coagulation. In vivo murine studies have demonstrated that activation of the JAK-STAT signaling pathway promotes neutrophil extracellular trap (NET) formation, contributing to a prothrombotic state. Insights from related clonal disorders such as paroxysmal nocturnal hemoglobinuria and the VEXAS syndrome support the concept that mutation-driven innate immune activation can directly perturb hemostatic balance. This review aims to summarize the association between clonal expansion of hematopoietic cells and thrombotic disease, and highlight how somatic mutations in hematopoietic cells may contribute to vascular disease and thrombogenesis. Full article

Diabetic nephropathy and diabetic atherosclerosis often develop together and share similar metabolic disturbances. Lipid abnormalities are common in diabetes, yet their roles in kidney and vascular injury are not fully understood. In diabetic kidney disease, altered lipid uptake, reduced fatty acid oxidation, and accumulation of harmful lipid species contribute to cellular stress, mitochondrial injury, inflammation, and fibrosis. In parallel, disordered lipid handling in the vasculature promotes endothelial dysfunction and atherosclerotic plaque development. However, not all lipid accumulation appears to be detrimental, and some findings suggest adaptive or context-dependent effects, leading to inconsistent results across studies. In this review, we summarize current evidence on lipid metabolism in diabetic nephropathy and atherosclerosis, compare shared and distinct features, and discuss ongoing controversies. We also briefly address the therapeutic relevance of targeting lipid pathways and highlight areas that require further investigation. Compared with prior reviews that mainly discussed fatty kidney as an emerging concept in chronic kidney disease research, this review specifically focuses on diabetic kidney disease and integrates kidney-specific lipid trafficking, kidney–vessel crosstalk, conflicting evidence, and mechanism-based therapeutic implications. Full article

Obesity drives chronic low-grade inflammation and endothelial dysfunction, key contributors to subclinical atherosclerosis. This review focuses on the netrin 1/UNC5B axis and its role in promoting macrophage retention within adipose tissue and atherosclerotic plaques, thereby perpetuating local inflammation and vascular injury. Complementary inflammatory markers—including IL 6, hsCRP, and IL 15—are discussed as indicators of systemic inflammatory burden, whereas endocan and ICAM 1 are briefly addressed as markers of endothelial activation. Among emerging pharmacological strategies, glucagon-like peptide-1 receptor agonists (GLP 1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) show the most consistent evidence for improving these biomarkers and reducing endothelial damage, with GLP 1RAs demonstrating direct effects on carotid intima–media thickness. Integrating biomarker profiling with obesity phenotypes may improve early risk stratification and support more precise management of subclinical atherosclerosis. Full article

Pulmonary arterial hypertension (PAH) is a severe and progressive cardiopulmonary disorder with limited treatment options. Camellia petelotii (Merr.) Sealy (CP) contains multiple flavonoids and other phytochemicals, but its active compounds and molecular mechanisms in PAH remain unclear. Active compounds of CP were screened by comprehensive literature mining and absorption, distribution, metabolism, and excretion (ADME) evaluation. PAH-related hub targets were identified from transcriptomic data using weighted gene co-expression network analysis (WGCNA), machine learning, and external validation. Functional enrichment, immune infiltration, and single-cell RNA-sequencing analyses were performed to characterize their biological roles and cellular localization. Molecular docking and molecular dynamics simulations assessed compound–target interactions. The effects of CP were further evaluated in hypoxia-induced rat pulmonary artery smooth muscle cells (RPASMCs). Five core bioactive compounds were identified, among which luteolin and quercetin were prioritized for further analysis. HSP90AA1 and ROCK2 were screened as hub targets. Bioinformatic analyses suggested that these targets were mainly associated with the “Lipid and atherosclerosis” pathway, metabolic reprogramming, and modulation of the immune microenvironment. Single-cell analysis showed broad expression of HSP90AA1 and enrichment of ROCK2 in fibroblasts and endothelial cells. Molecular docking and molecular dynamics simulations supported stable binding of luteolin to HSP90AA1. In vitro, CP extract inhibited hypoxia-induced hyperproliferation of RPASMCs and reduced HSP90AA1 protein expression. HSP90AA1 may represent a candidate molecular mediator of CP in PAH, and CP inhibited hypoxia-induced RPASMC proliferation in association with downregulation of HSP90AA1. Full article

Objectives: This study assessed the association between physical activity and vascular endothelial function and carotid atherosclerotic plaques in older adults using ultrasound imaging. Methods and Results: A total of 60 older adults were divided into three groups based on weekly physical activity: low (<4 h/week), moderate (4–12 h/week), and high (>12 h/week). All participants underwent flow-mediated dilation (FMD) assessment and carotid ultrasound to determine plaque burden. Participants with moderate physical activity demonstrated greater FMD (12.3 ± 2.5%) than those with low (1.2 ± 1.8%) or high activity (7.1 ± 1.3%), and a lower carotid plaque burden. In adjusted logistic regression models, moderate activity remained independently associated with a lower likelihood of impaired FMD (OR 0.22; 95% CI 0.18–0.27) and lower carotid plaque burden (OR 0.16; 95% CI 0.11–0.19). Conclusions: Moderate physical activity was associated with more favorable vascular endothelial function and reduced carotid atherosclerosis in older adults, indicating an association with a more favorable vascular profile. Full article

Nutraceuticals are emerging as promising agents for the prevention and treatment of atherosclerosis, particularly in light of the limitations associated with current pharmacotherapies. Pomegranate-derived polyphenols, especially punicalagin (PC), possess multiple cardioprotective properties. However, their direct biological effects are constrained by poor absorption and low bioavailability. Instead, many of their actions are mediated by gut microbiota-derived metabolites known as urolithins. Despite this, the roles of PC and its metabolites in atherosclerosis remain inadequately defined. The objective of this study was to investigate the anti-atherogenic effects and underlying mechanisms of PC and its major metabolites—ellagic acid and urolithins A, B, C, and D—using in vitro and in vivo approaches. In vitro, these compounds broadly inhibited key pro-atherogenic processes in macrophages and endothelial cells, including reactive oxygen species production and inflammatory gene expression, with notable metabolite-specific differences. Urolithin A (UA), identified as the most effective compound, was further evaluated in LDL receptor-deficient mice fed a high-fat diet. UA supplementation improved peripheral blood immune cell profile, reduced atherosclerotic plaque burden and inflammation, and enhanced markers of plaque stability. RNA sequencing of the thoracic aorta revealed key molecular pathways underlying the protective actions of UA. Collectively, these findings highlight the therapeutic potential of PC-derived metabolites, particularly UA, in combating atherosclerosis and support the need for future human clinical studies. Full article

Atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized not merely as a lipid-storage disorder but as a chronic, lipid-driven inflammatory condition of the arterial wall. Despite the widespread use of statins and other lipid-lowering therapies, a substantial “residual inflammatory risk” persists, propelling the search for targeted immunopharmacological interventions. At the forefront of this inflammatory cascade is the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which serves as a central orchestrator of vascular inflammation by linking metabolic dysregulation to the innate immune response. Atherogenic danger signals—such as oxidized low-density lipoprotein (ox-LDL) and cholesterol crystals—trigger NLRP3 activation through reactive oxygen species (ROS) generation, lysosomal rupture, and potassium efflux. This, in turn, drives the maturation of pro-inflammatory cytokines (IL-1β and IL-18) and initiates macrophage pyroptosis. In this review, we systematically evaluate the immunomodulatory potential of natural products—both complex extracts and single bioactive compounds—in inhibiting the NLRP3 inflammasome axis. We detail the pharmacological mechanisms by which these natural agents intercept inflammatory signaling at multiple stages: suppressing TLR4/NF-κB-mediated priming, scavenging mitochondrial ROS, and restoring autophagic flux via AMPK/mTOR pathways to prevent inflammasome assembly. By critically analyzing these pathways, we highlight natural product-derived inhibitors as a promising class of immunomodulators capable of attenuating atherosclerotic progression and addressing the persistent challenge of residual inflammatory risk. Full article

Metabolic reprogramming plays a critical role in the pathogenesis of cardiovascular diseases. Historically regarded as a metabolic waste product, lactate has recently emerged as a critical regulator of vascular biology, exerting both metabolic and signaling functions. Moreover, the discovery of protein lactylation, a novel post-translational modification derived from lactate, has revealed a direct link between metabolic flux and gene regulation. This review provides a comprehensive overview of the evolving roles of lactate and lactylation in cardiovascular physiology and disease, offering insights into potential therapeutic interventions. It first provides a historical perspective of lactate and lactylation, followed by an overview of lactate metabolism, lactate shuttle theory and signaling pathways. It then discusses the mechanism and regulation of lactylation, focusing on its writers, erasers, and readers. Finally, this review summarizes clinical implications of lactate and lactylation in various cardiovascular diseases, including atherosclerosis, pulmonary hypertension, myocardial infarction, heart failure, and diabetic vascular complications. A deeper understanding of the mechanisms underlying the lactate–lactylation axis may facilitate the development of new therapeutic strategies to prevent or treat cardiovascular diseases. Full article