Search Results (644)

Objective: While Sanzi Sijun Formula (SSF) has exhibited preliminary efficacy against metabolic dysfunction-associated steatotic liver disease (MASLD), its mode of action remains undefined. This study therefore aimed to unravel its core therapeutic mechanisms. Methods: UPLC-MS was employed to characterize the major components of SSF. Male C57BL/6J mice were fed a high-fat diet combined with high-fructose/glucose drinking water (HFD-HF/G) for 10 weeks to establish a MASLD model, followed by SSF intervention. After 8-week treatment, body and liver weight, hepatic histopathological alterations, serum levels of lipids, transaminase, and inflammatory cytokines were detected, and transcriptomic sequencing was performed on mouse liver tissues for mechanistic exploration. AML12 hepatocytes stimulated with palmitic acid (PA) were treated with SSF alone or in combination with AMPK or SIRT1 specific inhibitors. RT-qPCR and Western blotting were used to detect the expression or activation levels of AMPK, SIRT1, and key lipid metabolism-related molecules. Results: A total of 77 active components were identified in SSF by UPLC-MS analysis. In MASLD model mice, SSF significantly reduced body and liver weight, serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and alanine aminotransferase (ALT), suppressed the pro-inflammatory cytokines including TNF-α and IL-6, and elevated adiponectin levels. Histopathological staining demonstrated that SSF effectively alleviated hepatic steatosis, ballooning, and inflammatory cell infiltration. Transcriptomic profiling analysis verified the major regulatory effect of SSF on lipid metabolism and identified the AMPK/SIRT1 signaling pathway as a potential mechanism. Further experiments confirmed that SSF restored the levels of AMPK/ACC phosphorylation and SIRT1 expression, thereby modulating downstream lipid metabolism-related genes in liver tissues. In PA-induced AML12 cells, SSF significantly reduced intracellular accumulation of lipid and reactive oxygen species (ROS), which were partially abrogated by the inhibitors of AMPK or SIRT1. Conclusions: SSF exerts prominent effects against MASLD in both in vivo and in vitro models. Modulation of the AMPK/SIRT1 signaling pathway primarily contributes to its therapeutic mechanism against lipid metabolism disorder and lipotoxic liver injury. These findings provide experimental evidence to support the clinical application of SSF for MASLD treatment. Full article

Lipoprotein(a) (Lp(a)) is increasingly recognized as a genetically determined and clinically relevant contributor to residual cardiovascular risk. Through pro-atherogenic, pro-inflammatory, pro-thrombotic, and pro-calcific mechanisms, Lp(a) appears to play a significant role in both coronary artery disease and aortic valve disease. In patients undergoing percutaneous coronary intervention, elevated Lp(a) has been associated with worse long-term outcomes, including recurrent ischemic events, repeat revascularization, and in-stent restenosis, even in the setting of controlled low-density lipoprotein cholesterol. In parallel, experimental, genetic, and clinical data support a role for Lp(a) in the initiation and progression of calcific aortic stenosis, while its prognostic significance after transcatheter aortic valve interventions remains less clearly defined. Current guidelines now recognize Lp(a) as a relevant risk-enhancing factor, and emerging targeted therapies are achieving substantial reductions in circulating levels. Overall, Lp(a) should be regarded as both a meaningful biomarker and a promising therapeutic target, although ongoing outcome trials are needed to determine whether selective Lp(a) lowering translates into clinical benefit across interventional cardiovascular settings. The aim of this narrative review is to provide a single, comprehensive account of lipoprotein(a) [Lp(a)] in interventional cardiology, following this lipoprotein from its biology and pathophysiology through to its clinical impact and to the therapies that are now reaching the clinic, with a specific focus on the two most frequent catheter-based procedures in which it may carry prognostic weight: percutaneous coronary intervention (PCI) and transcatheter aortic valve implantation (TAVI). PCI and TAVI are deliberately addressed within the same review since they share a common upstream biology: Lp(a) contributes both to the atherosclerotic process that underlies coronary disease and to the calcific process that underlies aortic valve disease, and the corresponding patient populations overlap considerably in everyday interventional practice. Covering them together offers the interventional cardiologist a single, practical reference on how a patient with elevated Lp(a) may be approached in both scenarios. Full article

Cardiovascular disease (CVD) is closely linked to metabolic disorders such as obesity, dyslipidemia, and hepatic steatosis. This study investigated the anti-thrombotic and metabolic effects of KoreaGinseng F Max (KGF), a standardized extract rich in ginsenosides, in high-fat diet (HFD)-induced obese rats, and complementary in silico analyses were used to explore putative molecular targets and pathways. The extract was standardized to contain 36.97 mg/g of ginsenosides Rg1, Rb1, and Rf. Male rats were administered KGF (50, 100, or 200 mg/kg) orally for six weeks. KGF significantly improved lipid profiles by reducing serum triglycerides, total cholesterol, and low-density lipoprotein (LDL) levels. Histological analysis revealed a dose-dependent reduction in hepatic steatosis and adipocyte size. Potential anti-thrombotic activity was evaluated using a FeCl₃-induced carotid artery thrombosis model, with aspirin (30 mg/kg) included as a positive control. KGF200 delayed thrombus formation and produced a carotid blood flow pattern comparable to that observed in the aspirin-treated group, without significant alterations in serum ALT, AST, BUN, or creatinine levels. To further generate mechanistic hypotheses, complementary in silico analyses, including target prediction, GO/KEGG enrichment, network analysis, and molecular docking, were performed using the marker compounds. Eight overlapping genes, including STAT3, PTAFR, VEGFA, FGF2, HPSE, IL2, HSP90AA1, and LGALS3, associated with thrombotic regulation were identified. Pathway analysis suggested that PI3K–Akt signaling, calcium signaling, Th17 cell differentiation, and proteoglycan/ECM-related signaling may represent putative pathway-level mechanisms underlying the observed protective effects. Molecular docking suggested possible interactions between the marker ginsenosides and several predicted hub targets. Collectively, these findings suggest that KGF may have potential for further investigation as a natural product-derived material for improving HFD-associated metabolic and thrombotic dysfunction, while the predicted multi-target and multi-pathway effects require further experimental validation. Full article

Obesity is a global metabolic disease closely associated with dyslipidemia, insulin resistance, hepatic steatosis, and chronic oxidative stress. Cydonia oblonga Miller (COM, Quince) from Xinjiang Uygur Autonomous Region of China is a traditional medicinal and edible plant rich in polyphenols, flavonoids, polysaccharides, and other bioactive constituents. Our previous studies suggested that total polyphenols of Cydonia oblonga Miller (TPCOM) may exert promising anti-obesity effects. Objective: This study aimed to investigate the therapeutic effects of TPCOM on high-fat diet-induced obese C57BL/6 mice and to explore its underlying molecular mechanisms related to glycolipid metabolism. Methods: TPCOM was extracted and purified from Xinjiang Cydonia oblonga fruits, and its total polyphenol content was determined using the Folin–Ciocalteu method. C57 mice were randomly divided into normal diet, model, and TPCOM intervention groups. After 12 weeks of high-fat diet feeding and 6 weeks of TPCOM treatment, body weight was monitored continuously. Serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total antioxidant capacity (T-AOC) were measured using commercial kits. Hepatic pathological changes were observed by hematoxylin–eosin (HE) staining. Bioinformatics analyses including GO and KEGG were performed to predict key targets and pathways related to lipid metabolism. The protein expression levels of PPARGC1A, FFAR1, KLF15, Adipolin, GLUT4, and phosphorylated p38 MAPK in liver tissues were detected by Western blotting. Results: TPCOM intervention significantly reduced body weight gain in obese mice in a dose-dependent manner. Serum biochemical assays showed that TPCOM decreased TC, TG, and LDL-C levels, increased HDL-C levels, and markedly enhanced total antioxidant capacity (T-AOC). Bioinformatics analysis suggested that PPARG and FFAR1 were highly expressed in liver tissue and may participate in glucose and lipid metabolism regulation. Western blot results confirmed that TPCOM significantly upregulated the expression of PPARGC1A, FFAR1, KLF15, Adipolin, GLUT4, and phosphorylated p38 MAPK in the liver of obese mice. Conclusions: TPCOM effectively ameliorates obesity, dyslipidemia, hepatic steatosis, and oxidative stress in high-fat diet-induced obese mice. The underlying mechanism may be related to the regulation of glycolipid metabolism, mitochondrial function, insulin sensitivity, and antioxidant signaling via activating the FFAR1–PPARG–p38 MAPK axis and downstream targets including PPARGC1A, KLF15, Adipolin, and GLUT4. This study provides a scientific basis and theoretical support for the development and application of TPCOM as a natural functional ingredient in the prevention and adjuvant treatment of obesity and related metabolic disorders. Full article

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, and lowering low-density lipoprotein cholesterol (LDL-C) remains a cornerstone of cardiovascular prevention. Statins are among the most extensively studied and widely prescribed medications and have demonstrated substantial benefits in reducing major adverse cardiovascular events in both primary and secondary prevention settings. Nevertheless, the effectiveness of statin therapy in routine clinical practice is frequently compromised by poor adherence, treatment discontinuation, concerns regarding adverse effects, and persistent residual cardiovascular risk. This narrative review synthesises contemporary evidence relating to the mechanisms of action of statins, their role in primary and secondary prevention, determinants of medication adherence, statin-associated muscle symptoms (SAMSs), and emerging developments in precision cardiovascular medicine. Current evidence indicates that although statins remain highly effective in reducing cardiovascular risk, long-term treatment success is strongly influenced by behavioural, psychological, social, and healthcare system factors. Increasing attention has also been directed towards the multifactorial nature of SAMSs and the contribution of nocebo effects to perceived statin intolerance. Emerging approaches involving pharmacogenomics, artificial intelligence, digital health technologies, and multidimensional risk assessment offer opportunities for more individualised prevention strategies, although important limitations relating to cost, accessibility, and external validity remain. Overall, contemporary cardiovascular prevention requires a patient-centred approach that integrates biological, behavioural, and social determinants of health to optimise treatment adherence and improve long-term cardiovascular outcomes. Full article

Background: The highly heterogeneous and dynamically evolving tumor microenvironment leads to the development of drug resistance and recurrence in traditional therapies. Although immunotherapy demonstrates unique advantages, its clinical utility remains constrained by the suboptimal immunogenicity and the limited effect of monotherapy. Herein, a hybrid drug delivery system based on a spatiotemporal hierarchical controlled-release strategy was proposed to achieve dual immunotherapy with immune checkpoint blockade (ICB) and immunogenic cell death (ICD) to promote synergistic anti-tumor therapy. Methods: A liposome–micelle hybrid drug delivery system (RUT-RPP-LP) was constructed using a lipid bilayer composed of dioleoyl phosphatidylethanolamine/hemisuccinyl cholesterol to encapsulate rutin (RUT) and to form an inner cavity-encapsulated resveratrol micelle (RPP). RUT-RPP-LP was characterized, and its pH sensitivity and release behavior were investigated. Subsequently, a colon cancer tumor-bearing mouse model was constructed to evaluate the in vivo targeted anti-tumor effect and biological safety. On this basis, the combined mechanism of ICB and ICD was preliminarily explored. Results: RUT-RPP-LP possessed excellent formulation characteristics, stability, and biocompatibility, achieving graded controlled release of drugs via responding to the TME and lysosomal acidity, respectively. Obviously, RUT-RPP-LP could specifically target the tumor site, induce the occurrence of ICD, and simultaneously block the PD-1/PD-L1 immune checkpoint signaling pathway, thereby enhancing the function of T cells and inducing apoptosis of tumor cells. Conclusions: The RUT-RPP-LP based on the hierarchical controlled-release strategy exerted a spatiotemporally coordinated enhancement of anti-tumor immunity, and may provide a novel combinatorial approach to overcome the low response of immunotherapy in solid tumors. Full article

Excess adiposity increases cardiovascular and cardiometabolic risks, while aquatic exercise may reduce mechanical barriers to participation. This systematic review and meta-analysis examined aquatic exercise training in individuals with overweight or obesity. PubMed, Web of Science, and the Cochrane Library were searched through to June 2026. Eight randomized controlled trials involving 295 participants were included. Random-effects meta-analyses showed increased VO₂ max (MD 3.70 mL·kg⁻¹·min⁻¹, 95% CI 2.49–4.90; p < 0.001) and lower resting heart rate (MD −1.47 beats/min, 95% CI −2.73 to −0.21), systolic blood pressure (MD −4.50 mmHg, 95% CI −7.05 to −1.94), diastolic blood pressure (MD −2.17 mmHg, 95% CI −4.11 to −0.22), triglycerides (MD −15.75 mg/dL, 95% CI −23.12 to −8.39), and fasting glucose (MD −7.82 mg/dL, 95% CI −12.48 to −3.16). No significant pooled effects were observed for total cholesterol, HDL cholesterol, LDL cholesterol, BMI, or body fat percentage. Evidence certainty ranged from low to very low. Aquatic exercise may improve selected cardiovascular and metabolic outcomes, although small samples and heterogeneity limit confidence. Future research must focus on high-quality RCTs to further confirm these findings. PROSPERO: CRD420261340445. Full article

Background/Objectives: Cholesterol homeostasis is often framed as a dietary problem, but circulating low-density lipoprotein (LDL) biology is governed largely by endogenous sterol handling, with the liver acting as the principal integrative organ for cholesterol synthesis, LDL receptor-mediated clearance, very-low-density lipoprotein (VLDL) export, bile acid production, and biliary sterol disposal. This narrative review evaluates the hepatic basis of cholesterol regulation, statin pharmacology, gut microbial sterol metabolism, chronic hepatic inflammation, and a proposed oral–gut–liver–artery axis in atherogenesis. The aim of this narrative review is to clarify which elements of the proposed axis are established, which are supported but incomplete, and which remain hypothesis-generating. Methods: Mechanistic, translational, clinical, and review literature were synthesized to separate established mechanisms from emerging and speculative links. PubMed/MEDLINE, Scopus, and Google Scholar were searched from January 2000 through May 2026. Primary search terms included: cholesterol homeostasis, LDL receptor, SREBP2, statin pleiotropic effects, statin-associated muscle symptoms, gut microbiota cholesterol, bile salt hydrolase, MASLD, Porphyromonas gingivalis liver, phosphorylated dihydroceramides, serine dipeptide lipids Bacteroidetes, ceramide atherosclerosis, and oral–gut–liver–artery axis. Results: LDL/apoB causality and hepatic statin mechanism are well-established. Gut microbiota can alter cholesterol absorption, coprostanol formation, bile acid pools, and portal signaling, but these effects are context-dependent. Hepatic free cholesterol loading and lysosomal sterol stress are strongly implicated in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). Periodontal pathogens, especially Porphyromonas gingivalis, may contribute to liver and vascular inflammation through bacteremia, oral–gut translocation, innate immune activation, and bioactive bacterial sphingolipids. Phosphorylated dihydroceramides (PDHCs) and Bacteroidetes-derived serine dipeptide lipids have been detected in human arterial specimens and shown to enter host ceramide pools, providing a direct lipid metabolic pathway linking microbial community composition to vascular disease. Viridans streptococci and the Streptococcus anginosus group are inflammatory cofactors rather than proven causes of hepatic cholesterol overproduction. Conclusions: The strongest model involves microbial amplification of hepatic cholesterol dysmetabolism, endothelial activation, foam-cell formation, and plaque vulnerability acting on a host-derived LDL/apoB scaffold. This model is testable and should complement guideline-based LDL-lowering therapy. Full article

Background/Objectives: Lipid peroxidation is a relevant oxidative–inflammatory mechanism in essential hypertension and cardiovascular disease. Plasma thiobarbituric acid reactive substances (TBARS), commonly reported as malondialdehyde-equivalent values, provide an operational index of lipid peroxidation-related aldehydic reactivity, but blood-based assessment is limited by venipuncture and preanalytical handling requirements. Urine is an attractive non-invasive matrix for redox biomarker development, although whether urinary TBARS reflect plasma lipid peroxidation in hypertensive patients remains insufficiently characterized. This study aimed to evaluate whether matrix-specific normalization—total cholesterol for plasma TBARS and creatinine for urinary TBARS—reveals a measurable intra-individual relationship between these matrices in essential hypertension. Methods: In this paired observational study, plasma and urine samples were obtained from 39 treated patients with essential hypertension under standardized fasting conditions. TBARS were quantified using a colorimetric thiobarbituric acid reaction assay. Plasma TBARS were normalized to total cholesterol and expressed as TBARSp, while urinary TBARS were normalized to creatinine and expressed as TBARSu. Associations were assessed using Spearman’s rank correlation, exploratory receiver operating characteristic (ROC) analyses based on internally derived plasma TBARS percentile thresholds, and Bayesian bootstrap inference. Results: Cholesterol-normalized plasma TBARS and creatinine-normalized urinary TBARS showed a moderate-to-strong positive monotonic association (Spearman’s ρ = 0.717, p < 0.001). Bayesian bootstrap analysis supported this relationship, with a 95% credible interval of 0.57–0.83 and a Bayes factor > 300 for ρ ≥ 0.5. Urinary TBARS showed exploratory within-cohort discriminatory capacity for identifying elevated plasma TBARS using internally derived thresholds, with an AUC of 0.892 for the median-based classification. Conclusions: Creatinine-normalized urinary TBARS showed a moderate-to-strong association with cholesterol-normalized plasma TBARS in treated essential hypertension. These findings provide hypothesis-generating paired-sample evidence that urinary TBARS may serve as a low-burden, non-invasive proxy of plasma lipid peroxidation-related redox alterations. Further validation in larger and clinically diverse cohorts, ideally including more specific lipid peroxidation markers and renal-function-aware analyses, is required to define their translational and clinical utility. Full article

Lipoprotein(a) [Lp(a)] has emerged as a major genetically determined cardiovascular risk factor that extends beyond the traditional low-density lipoprotein cholesterol (LDL-C)-centred model of atherosclerotic disease. Despite optimal LDL-C lowering, a substantial proportion of patients continue to experience cardiovascular events, highlighting the clinical relevance of residual cardiovascular risk. This review summarizes current evidence regarding the epidemiology, genetics, pathophysiology and therapeutic implications of Lp(a) in cardiovascular disease. Epidemiological, genetic, and Mendelian randomization studies consistently demonstrate an independent and likely causal association between elevated Lp(a) and atherosclerotic cardiovascular disease, ischemic stroke, calcific aortic valve stenosis, heart failure, and recurrent cardiovascular events, even in patients with well-controlled LDL-C levels. Lp(a) promotes atherosclerosis through proatherogenic, proinflammatory, and prothrombotic mechanisms, largely mediated by oxidized phospholipids and the structural homology of apolipoprotein(a) with plasminogen. Current guidelines increasingly recognize Lp(a) as a risk-enhancing factor capable of refining cardiovascular risk stratification beyond traditional algorithms, thus recommending measuring Lp(a) at least once in a lifetime in all adults. Accurate measurement and standardization of Lp(a) remain essential in clinical practice due to apo(a) isoform size variability; reporting in molar concentrations (nmol/L) is preferred as it better reflects particle number being less affected by isoform size variations and improves the reliability of cardiovascular risk stratification. Collectively, these findings support the integration of Lp(a) into precision-based cardiovascular prevention strategies and suggest a paradigm shift from an exclusively LDL-centric approach toward genetically informed risk assessment and treatment. Full article

This study investigated the metabolic regulatory effects and underlying microbial mechanisms of Deinococcus radiodurans extract (DRE), using high-fat diet (HFD)-induced obese mice as the primary mechanistic model and naturally overweight felines. In the mouse model, a 1.5% DRE supplementation mitigated HFD-induced obesity, reduced serum total cholesterol and low-density lipoprotein levels, and markedly ameliorated hepatic steatosis. Fecal 16S rRNA gene sequencing revealed that DRE effectively reversed murine microbial dysbiosis by significantly restoring core commensals depleted by the HFD, notably Ureaplasma and the short-chain fatty acid (SCFA)-producer Odoribacter, while concurrently suppressing the overgrowth of obesity-associated taxa including Alloprevotella and Phascolarctobacterium. As a translational complement, a 28-day DRE intervention in felines under isocaloric maintenance conditions, with no significant change in body weight, body condition score, or fecal score, validated these systemic benefits, significantly enhancing serum total antioxidant capacity by 16.1% and reducing the systemic inflammatory marker serum amyloid A by 27.8%, indicating that the antioxidant and anti-inflammatory effects of DRE are independent of weight change. Concurrently, feline fecal microbiota profiling demonstrated a parallel ecological remodeling, characterized by the enrichment of potent SCFA producers (Oscillibacter and the [Eubacterium]_hallii_group) and the profound suppression of the pro-inflammatory pathogen Fusobacterium. Collectively, by integrating deep mechanistic insights from mice with translational evidence from felines, this study demonstrates that DRE exerts comprehensive anti-obesity and anti-inflammatory effects by regulating lipid metabolism and reshaping the gut microbiota, establishing its robust potential as a novel functional ingredient for metabolic health in companion animals. Full article

Objectives: This study aimed to examine the cross-sectional associations between serum folate concentrations and four lipid abnormality subtypes among community-dwelling adults in Zhejiang Province, China. Methods: This population-based cross-sectional study included 3254 adults from Zhejiang Province, China. Serum folate concentrations were analyzed both as quartiles and per 1-standard deviation (SD) increments. Multivariable logistic regression models were used to evaluate the associations of serum folate with hypercholesterolemia, hypertriglyceridemia, high low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C). Restricted cubic spline (RCS) regression models were further applied to assess dose–response patterns. Additional RCS analyses using continuous lipid parameters were also performed. False discovery rate (FDR) correction, exploratory subgroup analyses, and sensitivity analyses were additionally conducted. Results: The prevalences of hypercholesterolemia, hypertriglyceridemia, high LDL-C, and low HDL-C were 7.87%, 17.12%, 4.30%, and 4.46%, respectively. In the fully adjusted model, each 1-SD increment in serum folate was associated with lower odds of hypertriglyceridemia (OR = 0.82, 95% CI: 0.73–0.92) and low HDL-C (OR = 0.63, 95% CI: 0.49–0.81). Compared with the lowest quartile, participants in the highest serum folate quartile had lower odds of hypertriglyceridemia (OR = 0.62, 95% CI: 0.46–0.82) and low HDL-C (OR = 0.38, 95% CI: 0.22–0.64), with significant trends across quartiles (both p for trend < 0.001). No significant associations were observed for hypercholesterolemia or high LDL-C. These findings remained significant after FDR correction. RCS analyses suggested an overall inverse association between serum folate and hypertriglyceridemia, with no evidence of nonlinearity (p for overall = 0.001; p for nonlinearity = 0.212), whereas the association with low HDL-C showed evidence of nonlinearity (p for overall < 0.001; p for nonlinearity = 0.009). Additional RCS analyses using continuous lipid parameters showed broadly consistent findings for TG and HDL-C. Exploratory subgroup and sensitivity analyses showed generally similar results. Conclusions: Higher serum folate concentrations were cross-sectionally associated with lower odds of hypertriglyceridemia and low HDL-C among community-dwelling adults in Zhejiang Province, China, whereas no significant associations were observed for hypercholesterolemia or high LDL-C. Further prospective cohort studies are warranted to verify these cross-sectional findings and to explore underlying mechanisms. Full article

High levels of low-density lipoprotein cholesterol (LDL-c) have been recognized as the main causal factor of atherosclerotic cardiovascular disease (ASCVD) and are influenced by both genetic and environmental factors. Among genetic determinants, Familial Hypercholesterolemia (FH) is the most common monogenic disorder, caused by rare high-impact variants in genes involved in LDL uptake. Other monogenic causes of hypercholesterolemia include sitosterolemia, cerebrotendinous xanthomatosis and lysosomal acid lipase deficiency (LALD). However, monogenic disorders only account for a small proportion of inherited hypercholesterolemia. In many individuals, increased LDL-c levels are caused by the contemporary presence of different single-nucleotide polymorphisms (SNPs) with a moderate/low impact. These SNPs could be summarized through polygenic risk scores (PRS) that attribute relative weight to each of these. Another genetic determinant of hypercholesterolemic phenotypes is high levels of lipoprotein(a)—Lp(a). Lp(a) is an LDL particle modified by the binding of apolipoprotein(a)—apo(a)—which represents an independent risk factor for ASCVD. Lp(a) levels are mainly genetically determined by variation in the number of kringle IV type 2 (K-IV₂) repeats, as well as by several SNPs, and remain stable throughout life. The aim of this narrative review is to report an updated overview of the genetic mechanisms underlying hypercholesterolemia, including monogenic disorders, PRS and Lp(a), focusing on their potential repercussion in clinical practice by the integration into cardiovascular risk stratification beyond traditional clinical assessment. This integration could lead to a more comprehensive and individualized approach to cardiovascular prevention, with emerging perspectives including the possible use of artificial intelligence (AI). Full article

Modulation of cholesterol metabolism and reduction in serum cholesterol are key strategies for preventing cardiovascular diseases (CVDs). Functional foods enriched with dietary fiber and phytochemicals have attracted increasing attention for their potential health benefits. In this study, milk tablets containing kale and carrot (KC) were developed and preliminarily evaluated for their cholesterol-lowering potential. KC milk tablets were rich in dietary fiber, contained gallic acid, and exhibited antioxidant properties. They also supported the growth of Lactobacillus casei and Bifidobacterium longum in vitro, accompanied by increased SCFA production. In an open-label, pre–post exploratory study in hypercholesterolemic subjects, daily consumption for 6 weeks was associated with significantly increased HDL-C and reduced LDL-C levels. In addition, circulating ApoB100 and HMGCR levels were reduced, whereas ApoE and TNF-α remained unchanged. Therefore, these preliminary findings suggest that KC milk tablets may accomplish beneficial changes in lipid profiles and support the potential of dietary fiber–phenolic interactions with enhanced SCFA production which might modulate cholesterol metabolism. However, in further studies, randomized controlled trials are required to understand the precise underlying mechanism. Full article

Residual cardiovascular risk arises from dysregulated expression of genes encoding apolipoprotein(a) (LPA), apolipoprotein C-III (APOC3), angiopoietin-like gene 3 (ANGPTL3), and proprotein convertase subtilisin/kexin type 9 (PCSK9). RNA-based therapies, small interfering RNAs (siRNAs), and antisense oligonucleotides (ASOs) modulate these targets at the post-transcriptional level through RNA interference and RNase H-mediated degradation, respectively. This scoping review maps the molecular mechanisms, target involvement, and pharmacodynamic outcomes of RNA therapies for managing residual cardiovascular risk, with contextual comparison to traditional lipid-lowering agents. A systematic search of PubMed, Embase, Web of Science, and Scopus was performed from 2020 to February 2026. Of the 1088 records identified, 30 studies met the inclusion criteria. RNA therapies have demonstrated potential for engagement, with 80–98% reductions in Lp(a) (pelacarsen, olpasiran, zerlasiran, lepodisiran), 50–80% reductions in triglycerides (olezarsen, plozasiran, volanesorsen), and 36–44% reductions in low-density lipoprotein cholesterol (LDL-C). Mechanistically, siRNAs achieve gene silencing through RISC-mediated mRNA cleavage, with sustained pharmacodynamic effects (3–6 months) because of Argonaute-2 stability, while gapmer ASOs recruit RNase H1 for mRNA degradation. Conjugation with GalNAc allows for hepatocyte-specific delivery with a subcutaneous bioavailability of 70–85%. Safety profiles were favorable, with injection site reactions (4–12%) being the most common adverse event. This analysis maps the emerging molecular landscape of RNA therapies, highlighting their substantial precision for targeting residual cardiovascular risk pathways that cannot be addressed by traditional agents. Full article