Search Results (2,341)

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article

Moyamoya disease (MMD) is primarily associated with genetic variants in RNF213. RNF213 p.R4810K (c.14429G>A, p.Arg4810Lys) is a founder variant predominantly found in East Asian populations and is strongly associated with MMD, a rare cerebrovascular condition characterized by progressive stenosis of intracranial arteries and the development of abnormal collateral networks. Recent evidence suggests that RNF213 variants are also enriched in non-moyamoya intracranial arteriopathies, such as large-artery atherosclerotic stroke and intracranial arterial stenosis/occlusion (ICASO), particularly in east Asian individuals with early-onset or cryptogenic stroke. This expanded phenotypic spectrum, termed RNF213-related vasculopathy (RRV), represents a distinct pathogenic entity that may involve unique pathogenic processes separate from traditional atherosclerosis. In this review, we synthesize current genetic, clinical, radiological, and experimental findings that delineate the unique features of RRV. Patients with RRV typically exhibit a lower burden of traditional vascular risk factors, negative vascular remodeling in the absence of atheromatous plaques, and an increased propensity for disease progression. RNF213 variants may compromise vascular resilience by impairing adaptive responses to hemodynamic stress. Furthermore, emerging cellular and animal model data indicate that RNF213 influences angiogenesis, lipid metabolism, and stress responses, offering mechanistic insights into its role in maintaining vascular integrity. Recognizing RRV as a distinct clinical entity has important implications for diagnosis, risk stratification, and the development of genome-informed therapeutic strategies. Full article

Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) alleviate stress on multiple organs. SGLT2i has been demonstrated to benefit heart failure, hemodynamic regulation, and renal protection while GLP-1RA on the other hand has been shown to demonstrate a strong impact on glycemic management, weight loss, and atherosclerotic cardiovascular disease. This review will aim to understand and evaluate the mechanistic rationalization, clinical evidence, and the potential therapeutic treatment of SGLT2 inhibitors and GLP-1 receptor agonists to treat individuals who have CKM syndrome. This analysis also assesses whether combination therapy can be a synergistic approach that may benefit patients but is still underutilized because of the lack of clear guidelines, the associated costs, and disparities in accessibility. Therefore, in this review, we will be discussing the combination therapy’s additive and synergistic effects, current recommendations and clinical evidence, and mechanistic insights of these GLT2 inhibitors and GLP-1 receptor agonists in CKM syndrome patients. Overall, early and combination usage of GLP-1RA and SGLT2i may be essential to demonstrating a significant shift in modern cardiometabolic therapy toward patient-centered care. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. Hibiscus leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (−)-epicatechin gallate (ECG). Despite ECG’s well-known pharmacological activities and its total antioxidant capacity being stronger than that of other catechins, its regulatory effects on MASLD have not been fully described previously. Therefore, this study attempted to evaluate the anti-MASLD potential of ECG isolated from Hibiscus leaves on abnormal lipid and glucose metabolism in hepatocytes. First, oleic acid (OA) was used as an experimental model to induce lipid dysmetabolism in human primary hepatocytes. Treatment with ECG can significantly (p < 0.05) reduce the OA-induced cellular lipid accumulation. Nile red staining revealed, compared to the OA group, the inhibition percentages of 29, 61, and 82% at the tested doses of ECG, respectively. The beneficial effects of ECG were associated with the downregulation of SREBPs/HMGCR and upregulation of PPARα/CPT1 through targeting AMPK. Also, ECG at 0.4 µM produced a significant (p < 0.01) decrease in oxidative stress by 83%, and a marked (p < 0.05) increase in glycogen synthesis by 145% on the OA-exposed hepatocytes with insulin signaling blockade. Mechanistic assays indicated lipid and glucose metabolic homeostasis of ECG might be mediated via regulation of lipogenesis, fatty acid β-oxidation, and insulin resistance, as confirmed by an AMPK inhibitor. These results suggest ECG is a dual modulator of lipid and carbohydrate dysmetabolism in hepatocytes. Full article

Background/Objectives: Nowadays, intravascular lithotripsy (IVL) has emerged as a novel technique for treatment of vascular calcifications, first in coronary and then in peripheral arteries. In the current literature there is little evidence that describes IVL as an effective and safe solution in treating severe aortic and aorto-iliac calcifications. The aim of this study is to report current available data about the use of IVL in treating aortic and aorto-iliac calcified lesions and its application in facilitating other endovascular procedures. Methods: the present review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Guidelines. Preliminary searches were conducted on MEDLINE and Pubmed from January 2015 to February 2025. Studies were divided into 3 main categories depending on the location of calcifications and the type of treatment: IVL in visceral and infrarenal obstructive disease (group 1), IVL in aorto-iliac obstructive disease (group 2), IVL used to facilitate other endovascular procedures. Main primary outcomes in the perioperative period were technical and clinical successes and perioperative complications. Primary outcomes at 30 days and mid-term (2 years) were overall survival, limb salvage rate, primary patency, primary assisted patency, secondary patency, and residual stenosis. Results: Sixteen studies were identified for a total of 1674 patients. Technical and clinical successes were 100%, with low rates of perioperative complications. Dissection rate reaches up to 16.1% in some studies, without any differences compared to plain old balloon angioplasty (POBA) alone (22.8%; p = 0.47). At 30 days, limb salvage and survival rates were 100%. At 2 years, primary patency, assisted primary patency, and secondary patency were 95%, 98%, and 100%, respectively, with no difference compared to IVL + stenting. Conclusions: IVL has emerged as a novel approach to treat severe calcified lesions in visceral and aorto-iliac atherosclerotic disease and to facilitate other endovascular procedures. This technique seems to offer satisfactory early and mid-term outcomes in terms of primary, primary assisted patency, and secondary patency with low complication rates. Full article

Coronary artery disease (CAD) is the main cause of morbidity and death worldwide, and atherosclerosis represents the leading pathophysiological pathway responsible for CAD. Atherosclerotic process is a complex interplay of mechanisms and mediators resulting in plaque formation, progression and destabilization, the latter being the most frequent cause of acute cardiovascular events. Considering the systemic nature of atherosclerosis, polyvascular disease involvement is possible and has been described since 1960s. Accordingly, epidemiologic studies reported that concomitant CAD and atherosclerosis in other arterial beds like carotid arteries, lower limb arteries, mesenteric and renal circulation, and aorta, is frequent and related to increased chance of future cardiovascular events. Although risk factors, atherosclerotic plaque features and mechanisms of plaque destabilization are largely shared across different sites, many studies have reported some disparities among districts. Moreover, simultaneous polyvascular disease has been associated with increased likelihood of having particular plaque characteristics depending on the affected arterial level. In this comprehensive narrative review, we aim to discuss about epidemiology of concomitant CAD and atherosclerosis in other arterial beds, and to examine differences in risk factors, plaque features and mechanisms of plaque instability between CAD and other atherosclerotic locations. Finally, we review the studies observing differences on plaque features according to involved atherosclerotic sites, focusing on CAD. Full article

Optical Coherence Tomography (OCT) has evolved from a breakthrough ophthalmologic imaging tool into a cornerstone technology in interventional cardiology. After its initial applications in retinal imaging in the early 1990s, OCT was subsequently envisioned for cardiovascular use. In 1995, its ability to visualize atherosclerotic plaques was demonstrated in an in vitro study, and the following year marked the acquisition of the first in vivo OCT image of a human coronary artery. A major milestone followed in 2000, with the first intracoronary imaging in a living patient using time-domain OCT. However, the real inflection point came in 2006 with the advent of frequency-domain OCT, which dramatically improved acquisition speed and image quality, enabling safe and routine imaging in the catheterization lab. With the advent of high-resolution, second-generation frequency-domain systems, OCT has become clinically practical and widely adopted in catheterization laboratories. OCT progressively entered interventional cardiology, first proving its safety and feasibility, then demonstrating superiority over angiography alone in guiding percutaneous coronary interventions and improving outcomes. Today, it plays a central role not only in clinical practice but also in cardiovascular research, enabling precise assessment of plaque biology and response to therapy. With the advent of artificial intelligence and hybrid imaging systems, OCT is now evolving into a true precision-medicine tool—one that not only guides today’s therapies but also opens new frontiers for discovery, with vast potential still waiting to be explored. Tracing its historical evolution from ophthalmology to cardiology, this narrative review highlights the key technological milestones, clinical insights, and future perspectives that position OCT as an indispensable modality in contemporary interventional cardiology. As a guiding thread, the myth of Prometheus is used to symbolize the evolution of OCT—from its illuminating beginnings in ophthalmology to its transformative role in cardiology—as a metaphor for how light, innovation, and knowledge can reveal what was once hidden and redefine clinical practice. Full article

Background and Objectives: Galectin-3 (Gal-3), a pro-inflammatory cytokine, has been implicated in atherosclerosis and adverse cardiovascular outcomes. While its role in coronary artery disease (CAD) is increasingly recognized, its association with systemic atherosclerosis remains underexplored. Objective: To investigate serum Gal-3 levels in patients with CAD and evaluate correlations between CAD severity and extra-coronary atherosclerotic involvement (carotid, femoral, and radial territories). Materials and Methods: We prospectively enrolled 56 patients with CAD undergoing coronary angiography (42.8% with acute-ACS; 57.2% with chronic coronary syndromes-CCS). Gal-3 levels were measured within 24 h of admission. Atherosclerosis severity was assessed angiographically and through vascular ultrasound of the carotid, femoral, and radial arteries. Patients were stratified by median Gal-3 levels, and clinical follow-up was performed at 1 and 3 months. Results: Gal-3 levels were significantly higher in CAD vs. controls (20.7 vs. 10.1 ng/mL; p < 0.00001) and in ACS vs. CCS (22.18. vs. 17.93 ng/mL; p = 0.019). Gal-3 correlated positively with culprit lesion diameter stenosis (DS) (R = 0.30; p = 0.023) and maximum severity of additional treated lesions (R = 0.62; p = 0.006). Gal-3 also correlated positively with carotid plaque thickness (R = 0.32; p = 0.016), while patients with Gal-3 levels above the median showed increased median values for femoral plaque thickness (32.4 vs. 26.45 mm, p = 0.046). No correlation was found with radial artery calcification. Gal-3 showed moderate discrimination for ACS (AUC = 0.685; cut-off 20.18 ng/mL). On multivariate analysis age, DS, and ACS presentation were independent predictors of Gal-3 above 19.07 ng/mL. Conclusions: Gal-3 levels are elevated in ACS and correlate with atherosclerotic burden, particularly in coronary, carotid, and femoral territories. These findings support Gal-3 as a potential marker of lesion severity and systemic vascular involvement, highlighting its possible role in risk stratification and the monitoring of atherosclerotic disease progression. This study provides integrated insights into the impact of Gal-3 across multiple vascular beds by assessing them concurrently within the same patient cohort. Full article

Unhealthy dietary patterns are a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). International guidelines recommend reducing saturated fatty acid intake while increasing polyunsaturated and monounsaturated fatty acids (MUFAs) to mitigate cardiovascular risk. However, evidence regarding MUFAs and risk of ASCVD remains conflicting, with recent studies raising concern about a potential higher risk associated with MUFA intake. The aim of this narrative review is to provide an overview of current knowledge and gaps in the literature regarding MUFAs and the risk of ASCVD with a focus on intake, individual types, and content in adipose tissue as a biomarker of endogenous exposure. Main findings reveal that most studies have inappropriately combined all MUFAs together, despite individual MUFA types having different biological effects and showing varying correlations between dietary intake and adipose tissue content. Adipose tissue composition may serve as a biomarker of long-term MUFA exposure, reflecting cumulative intake over one to two years while minimizing biases inherent in dietary assessments. However, tissue levels reflect both dietary intake and endogenous synthesis, complicating interpretation. Importantly, the source of MUFAs appears critical, with plant-derived MUFAs potentially offering advantages over animal-derived sources. In conclusion, we suggest that future research should focus on individual MUFA types rather than treating them as a homogeneous group, investigate their specific dietary sources and associations with ASCVD risk, and use adipose tissue biomarkers to improve exposure assessment and clarify causal relationships while considering overall dietary patterns. Full article

Advances in plaque imaging have transformed cardiovascular diagnostics through detailed characterization of atherosclerotic plaques beyond traditional stenosis assessment. This review outlines the clinical applications of varying modalities, including dual-layer spectral CT, photon-counting CT, dual-energy CT, and CT-derived fractional flow reserve (CT-FFR). These technologies offer improved spatial resolution, tissue differentiation, and functional assessment of coronary lesions. Additionally, artificial intelligence has emerged as a powerful tool to automate plaque detection, quantify burden, and refine risk prediction. Collectively, these innovations provide a more comprehensive approach to coronary artery disease evaluation and support personalized management strategies. Full article

Background/Objectives: Elevated serum uric acid levels are associated with the occurrence, development, and adverse events of coronary heart disease (CHD) and CHD risk factors. However, the extent of any pathogenic effect of the serum uric acid on CHD and whether CHD risk factors play a confounding or mediating role are still unclear. Methods: The potential causal associations of serum uric acid with CHD were evaluated via cross-trait linkage disequilibrium score regression analysis and Mendelian randomization. The pleiotropy of genetic tools was analyzed via a Bayesian colocalization approach. Moreover, we utilized two-step MR to identify risk factors mediating the relationship between uric acid and CHD. Results: Mendelian randomization results derived from two genetic instrument selection strategies support that serum uric acid levels have a significant causal relationship with coronary artery disease, stable angina pectoris, and myocardial infarction. This causal relationship was partially mediated by diastolic blood pressure, mean arterial pressure, and serum triglycerides. Transcriptomic analysis revealed that serum uric acid may directly contribute to the development of atherosclerosis by inducing transcriptomic changes in macrophages. Conclusions: Our findings highlight that the control of serum urate concentration in the long-term management of CHD patients may be necessary. Well-designed clinical trials and foundational research are presently required to furnish conclusive proof regarding the specific clinical scenarios in which adequate reduction in urate concentrations can confer cardiovascular advantages. Full article

Metabolic syndrome (MetS) is defined as a group of metabolic defects that include hypertension, insulin resistance, visceral obesity, fatty liver disease, and atherosclerotic cardiovascular disease (CVD). The first step in controlling the progression of MetS is lifestyle changes, including dietary modification. Regular consumption of fruits, vegetables, whole grains and other plant foods negatively correlates with the risk of developing chronic diseases. Green leafy vegetables (GLVs) are a key element of healthy eating habits and an important source of vitamins C and E, carotenoids—mainly β-carotene and lutein—and minerals. This review discusses and summarizes the current knowledge on the health benefits of consuming GLVs in the prevention and treatment of MetS to provide a compendium for other researchers investigating new natural products. Full article

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized, non-atherosclerotic cause of acute coronary syndrome (ACS), particularly in younger women. This comprehensive review outlines SCAD’s unique pathophysiology, which is linked to underlying arteriopathies like fibromuscular dysplasia, and highlights the critical role of advanced intravascular imaging for accurate diagnosis. A fundamental shift in management is detailed, with evidence favoring a conservative strategy for stable patients due to high rates of spontaneous vessel healing, reserving technically challenging invasive interventions for high-risk cases. Importantly, this review also addresses long-term outcomes, noting significant rates of recurrence and Major Adverse Cardiac Events (MACE), a high prevalence of persistent chest pain, and the central role of beta-blocker therapy in secondary prevention. Ultimately, SCAD requires a departure from standard ACS protocols towards a personalized approach that emphasizes accurate diagnosis, cautious initial management, and vigilant long-term follow-up. Full article

Background and aim: ANGPTL3 is a hepatokine acting as a negative regulator of lipoprotein lipase (LPL) through its N-terminal domain. Besides this activity, the C-terminal domain of ANGPTL3 interacts with integrin αVβ3. Since integrins are involved in inflammation and in the initiation of atherosclerotic plaque, the aim of our study was to evaluate the potential direct pro-inflammatory action of ANGPTL3 through the interaction of the fibrinogen-like domain and integrin αVβ3. Methods: We utilized cultured THP-1 human-derived macrophages and evaluated their pro-inflammatory phenotype in response to treatment with human recombinant ANGPTL3 (hANGPTL3). By Western blot, RT-qPCR, biochemical analysis, and ELISA assays, we determined the expression of genes and proteins involved in lipid metabolism and inflammatory response as well as intracellular cholesterol and triglyceride levels. In addition, we evaluated the effect of hANGPTL3 on the cellular cholesterol efflux process. Results: Incubation of THP-1-derived macrophages with 100 ng/mL of hANGPTL3 increased the mRNA expression of the pro-inflammatory cytokines IL-1β, IL-6, and TNFα (respectively, 1.87 ± 0.08-fold, 1.35 ± 0.11-fold, and 2.49 ± 0.43-fold vs. control). The secretion of TNFα, determined by an ELISA assay, was also induced by hANGPTL3 (1.98 ± 0.4-fold vs. control). The pro-inflammatory effect of hANGPTL3 was partially counteracted by co-treatment with the integrin αVβ3 inhibitor RGD peptide, reducing the mRNA levels of IL-1β (3.35 ± 0.35-fold vs. 2.54 ± 0.25-fold for hANGPTL3 vs. hANGPTL3 + RGD, respectively). Moreover, hANGPTL3 reduced cholesterol efflux to apoA-I, with a parallel increase in the intracellular triglyceride and cholesterol contents by 31.2 ± 2.8% and 20.0 ± 4.1%, respectively, compared to the control. Conclusions: ANGPTL3 is an important liver-derived regulator of plasma lipoprotein metabolism, and overall, our results add a new important pro-inflammatory activity of this circulating protein. This new function of ANGPTL3 could also be related to triglyceride and cholesterol accumulation into macrophages. Full article

Atherosclerosis (AS) is a complex pathological process characterized by the pivotal involvement of foam cells in its pathogenesis. As the primary cellular components of arterial plaques, foam cells critically determine plaque stability. Foam cells derive mainly from macrophages, and their formation is driven by dysregulated lipid metabolism within these immune cells. Macrophage cholesterol metabolism is a highly regulated process comprising four key phases: uptake, esterification, hydrolysis, and efflux. Under physiological conditions, these four phases maintain a delicate balance. However, disruption of cholesterol homeostasis results in the excessive accumulation of intracellular lipid, promoting the formation of foam cell and inflammasome activation, thereby accelerating the atherosclerotic progression. Therefore, targeting macrophage cholesterol metabolism has emerged as a promising therapeutic approach for AS. This review summarizes the mechanisms underlying macrophage cholesterol metabolism and highlights recent progress in identifying bioactive components of traditional Chinese medicines (TCMs) that mitigate AS through the modulation of macrophage cholesterol homeostasis. These findings may offer novel insights into the development of clinically effective therapies for the prevention of AS. Full article