Search Results (568)

Background/Objectives: The efficacy of two-stent implantation with iStent inject W is well established for mild-to-moderate open-angle glaucoma (OAG), whereas evidence for three-stent implantation with iStent infinite in severe OAG remains limited. We compared 12-month outcomes of a severity-based surgical strategy, using two stents in mild-to-moderate OAG and three stents in severe OAG. Methods: This retrospective study included 100 eyes with OAG that were followed for at least 12 months after trabecular micro-bypass stent implantation. Eyes with mild-to-moderate disease, defined as visual field mean deviation (MD) of −12 dB or better, received two stents (iStent inject W), whereas eyes with severe disease, defined as MD worse than −12 dB, received three stents (iStent infinite). Outcomes included intraocular pressure (IOP), glaucoma medication burden, visual field parameters, corneal endothelial cell density (ECD), surgical success, and additional glaucoma surgery. Results: Baseline IOP and the number of glaucoma medications were higher in the three-stent group. At 12 months, mean IOP was similar between groups. Although the three-stent group showed a greater unadjusted reduction in IOP, this difference was not significant after adjustment for baseline IOP using analysis of covariance. Linear mixed-model analysis also showed no significant group effect or time-by-group interaction. Glaucoma medications decreased significantly in both groups, with a similar mean reduction, although the three-stent group had a greater medication burden at 12 months. Changes in visual field parameters and corneal ECD did not differ significantly between groups. Surgical success and the need for additional glaucoma surgery were also not significantly different between groups. Conclusions: In this retrospective cohort, three-stent implantation in severe OAG was associated with 12-month IOP outcomes similar to those observed in the two-stent group with mild-to-moderate OAG, although this was achieved with a greater residual medication burden. This approach appears feasible for patients with severe OAG. Full article

Disruptions in folate (vitamin B9) and vitamin B12 metabolism, including nutritional deficiency, folate receptor alpha (FRα) autoantibodies, and MTHFR/DHFR polymorphisms, impair one-carbon metabolism and produce measurable retinal structural, microvascular, and functional changes, offering a non-invasive window into systemic and cerebral metabolic dysfunction, particularly cerebral folate deficiency (CFD). This review synthesizes peer-reviewed evidence on retinal alterations linked to folate/B12 deficiency, hyperhomocysteinemia, FRα autoantibody syndromes, and MTHFR/DHFR variants, alongside artificial intelligence (AI) and machine learning (ML) approaches applied to retinal imaging for metabolic, anemic, and nutritional optic neuropathy detection. Three convergent phenotypes emerge: structural changes (retinal nerve fiber layer and ganglion cell complex thinning, optic disc pallor, chorioretinal atrophy), microvascular abnormalities (reduced vessel density, foveal avascular zone enlargement, capillary dropout), and functional deficits (centrocecal scotoma, dyschromatopsia, reduced contrast sensitivity); they arise from homocysteine-mediated endothelial toxicity, mitochondrial impairment, and eNOS uncoupling. Existing AI/ML models for anemia and optic neuropathy establish technical feasibility but do not target folate-specific phenotypes. We propose a dedicated multimodal ML framework integrating structural, perfusion, functional, and biochemical/genetic data as a research agenda for automated, non-invasive CFD detection. Given the established folate–autism spectrum disorder (ASD) risk association reported in FRAA-positive cohorts, such a framework, once validated, could support prenatal and neonatal screening in FRAA-positive or genetically high-risk pregnancies, enabling earlier leucovorin treatment and reducing neurodevelopmental risk. Full article

Patients with autoimmune rheumatic diseases, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), experience excess cardiovascular risk that is not fully captured by conventional lipid measurements. In active RA, lower cholesterol may coexist with higher vascular risk, a pattern known as the lipid paradox. We propose that systemic inflammation can uncouple lipid concentration from lipoprotein function and organize the evidence along five mechanistic axes. Inflammatory cytokines, mainly interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), IL-1β, IL-17/IL-23 and type I interferons, remodel lipoprotein metabolism. High-density lipoproteins (HDL) lose protective functions and may become pro-inflammatory. Apolipoprotein-B particles are oxidized or otherwise modified, linking lipid metabolism to autoimmunity. Macrophage cholesterol imbalance and cholesterol crystals activate inflammasome pathways in experimental atherosclerosis, while immune-cell metabolic rewiring may amplify cytokine output; these mechanisms are treated as extrapolated when direct rheumatic-disease evidence is limited. The pathways converge on endothelial dysfunction and thrombo-inflammation. RA and SLE are the mechanistic anchors, whereas psoriatic disease, axial spondyloarthritis, systemic sclerosis, vasculitides and antiphospholipid syndrome are weighted by evidence category. Standard lipid panels may therefore underestimate risk in selected contexts, especially during active inflammatory disease. Full article

MicroPulse laser trabeculoplasty (MLT) lowers intraocular pressure (IOP) with subthreshold pulses that spare the surrounding tissue, yet its effect on the corneal endothelium is far less studied than that of selective laser trabeculoplasty, and almost unstudied in treatment-naïve eyes. We retrospectively reviewed 70 treatment-naïve glaucoma patients (one eye each) treated with a 577 nm yellow laser (Easyret^®) in micropulse mode (300 µm, 300 ms, 1000 mW, 360°). Endothelial cell density, mean cell area, hexagonality, the coefficient of variation in cell size, and central corneal thickness were recorded by specular microscopy (SP-1P, Topcon), and IOP by Goldmann applanation, at baseline and 1, 3, and 6 months. Linear mixed-effects models used every available observation, so no patient was excluded for a missed visit. IOP fell from 25.9 ± 2.5 mmHg to 20.6 and 21.0 mmHg at one and three months (−5.32 and −5.00 mmHg, roughly 20%; both p < 0.001), then returned to 24.8 mmHg by six months, and the proportion reaching a 20% reduction fell from 62.5% to 4.6%. Endothelial cell density, mean cell area, and central corneal thickness held steady, and every morphological change stayed within the device’s repeatability limits on equivalence testing. MLT lowered IOP early but transiently; over six months no clinically meaningful change in corneal endothelial morphology was detected. Full article

Background/Objectives: To evaluate the association between demographic, ocular biometric, and systemic comorbidity variables with corneal endothelial morphometric parameters in a Caucasian adult population undergoing cataract surgery. Methods: Cross-sectional study in a large cohort of patients who were candidates for cataract surgery with no other concomitant ocular pathology. Endothelial cell density (ECD), hexagonality (HEX), the coefficient of variation (CV), and the presence of guttae were assessed using specular microscopy (Tomey EM-4000). Biometric parameters were obtained by partial coherence interferometry (IOLMaster 700), and systemic comorbidities were recorded. Multiple linear regression models adjusted for age and sex were applied, along with stratified analyses according to axial length (AL). Results: A total of 1032 eyes from 1032 patients were included. The mean age was 75.9 ± 9.3 years. The cohort comprised 366 men (35.5%) and 666 women (64.5%). The mean ECD was 2113 ± 544 cells/mm², HEX 42.7 ± 21.6%, and CV 43.2 ± 9.6%. The prevalence of guttae was 15.4% (159 eyes). ECD correlated negatively with age (r = −0.148; p < 0.001) and positively with central corneal thickness (r = 0.091; p = 0.004) and anterior chamber depth (r = 0.064; p = 0.030). In the multivariate model, age was independently associated with lower ECD (β = −8.40 cells/mm²/year; p < 0.001), whereas male sex was associated with higher ECD and lower CV. No significant associations were found with AL, keratometry, or systemic comorbidities. Stratified analysis by AL group showed consistent patterns with no relevant differences. Conclusions: Corneal endothelial morphometry in Caucasian adults is primarily associated with age, sex, central corneal thickness, and anterior chamber depth, with no significant association with axial length or systemic comorbidities. 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

This prospective multicenter study evaluated the safety and clinical performance of ultra-high Dk (180 ISO/Fatt) Tisilfocon A orthokeratology (Ortho-K) lenses to treat myopia. We enrolled 67 participants aged 8–49 years with myopia up to 8.00 D. Participants were followed for 36 weeks to assess uncorrected visual acuity (UCVA), axial length (AL), and corneal endothelial cell density (ECD). From the first week, UCVA significantly improved and remained stable through week 36. AL elongation was statistically significant overall, driven primarily by age-appropriate physiological growth in younger participants; adults and individuals with high myopia showed no significant axial elongation. Safety evaluations showed high biocompatibility with no adverse events exceeding Grade 2 corneal staining. ECD remained stable after 36 weeks of lens wear, demonstrating that the ultra-high oxygen permeability of Tisilfocon A supports corneal health and prevents hypoxic stress during overnight wear. Overall, these findings suggest that ultra-high Dk Tisilfocon A Ortho-K lenses are a safe and effective clinical solution for myopia management across diverse patients, providing long-term corneal integrity and stable visual outcomes. ECD remained stable over the 36-week observation period, providing reassuring short- to mid-term evidence that the ultra-high oxygen permeability of Tisilfocon A may help limit hypoxic stress during overnight wear. Overall, these findings suggest that ultra-high Dk Tisilfocon A Ortho-K lenses are well tolerated and clinically effective across diverse patients during this period; however, in the absence of a concurrent control group and given the relatively short follow-up, these results should be regarded as preliminary, and longer-term controlled studies are needed to confirm the durability of axial length control and corneal endothelial safety. Full article

Apolipoprotein A1 (APOA1) and paraoxonase 1 (PON1) are key proteins of high-density lipoproteins (HDL). The aim of the present study was to obtain and characterize an in vitro model for endogenous APOA1 and PON1 longstanding upregulation in hepatocytes that can be further used to decipher the mechanisms of their protective action. Cultured human hepatocytes (HuH-7 cell line) were transfected with CRISPR/dCas9 activation plasmids targeting APOA1/PON1 genes. Following selection with specific antibiotics, RNA sequencing was used for the transcriptomic characterization of the transfected hepatocytes. The functionality of the secreted APOA1/PON1 was evaluated as the capacity of the conditioned medium (CM) from transfected HuH-7 to modulate the oxidative and inflammatory stress in TNFα-activated primary human umbilical endothelial cells (HUVEC). The results showed that: (1) a robust, longstanding upregulation (46 days) of endogenous APOA1/PON1 was obtained after CRISPR/dCas9 transfection and antibiotics selection; (2) APOA1/PON1 upregulation led to a modified transcriptomic profile and increased the expression of several antioxidant genes in transfected hepatocytes as demonstrated by RNAseq analysis; (3) secreted APOA1/PON1 were functional as demonstrated by the CM ability to reduce the levels of reactive oxygen species and inflammatory markers (VCAM-1, MCP-1) in TNFα-activated HUVEC. In conclusion, we achieved an experimental model of successful longstanding upregulation of endogenous APOA1 and PON1 in human hepatocytes. The targeted proteins are secreted in a functional form and can be used for deciphering their complex mechanism of protective action in various pathological conditions. Full article

Introduction: Endothelial dysfunction (ED) is a key pathogenetic mechanism underlying cardiovascular and cerebrovascular diseases and is increasingly recognized as a common link between ischemic heart pathology and cerebral vascular impairment. In addition to postnatal risk factors, adverse intrauterine conditions, particularly prenatal hypoxia (PH), may program long-term endothelial alterations. The aim of this study was to investigate the structural and molecular features of ED in the myocardial and cerebral vessels in experimental chronic heart failure (CHF) and PH, as well as to evaluate the endothelioprotective potential of pharmacological agents targeting the nitric oxide system. Methods: This study was conducted on Wistar rats using experimental models of CHF (doxorubicin administration, cumulative dose 15 mg/kg) and PH (sodium nitrite 50 mg/kg administered to pregnant females on gestational days 16–21). The endothelial status of cerebral and myocardial vessels was assessed using immunohistochemistry, ELISA, morphometric analysis, and real-time PCR. Key markers of endothelial function, inflammation, nitric oxide metabolism, oxidative stress, and angiogenesis were evaluated. The endothelioprotective potential of nitric oxide-modulating pharmacological agents was also evaluated. Results: CHF and PH induced pronounced structural and functional endothelial alterations in the microcirculatory and muscular-type vessels of the heart and brain. These changes were characterized by reduced endothelial cell density, suppressed eNOS expression, increased iNOS expression, nitric oxide deficiency, elevated nitrotyrosine levels, and activation of proinflammatory cytokines. VEGF levels were significantly decreased, while apoptotic features of endothelial cells were intensified. Angiolin and Hypertril demonstrated the most pronounced endothelioprotective effects among the tested agents. Conclusions: CHF and PH induce persistent ED in cerebral and myocardial vessels through disruption of the nitric oxide system, oxidative stress, and inflammatory activation. PH may act as an early trigger increasing susceptibility to cardiovascular and cerebrovascular diseases later in life. These findings support the rationale for targeted endothelioprotective therapy in ischemic cardiovascular pathology. Full article

Endothelial dysfunction is an early event in the development of cardiovascular diseases and is characterized by impaired barrier function, inflammatory activation of endothelial cells (ECs), and alterations in lipid metabolism. In addition to typical (mononuclear) endothelial cells (TECs), multinucleated variant endothelial cells (MVECs) are present within the vascular wall; however, their functional role remains poorly understood. The aim of the present study was to investigate the molecular and functional characteristics of MVECs and their potential contribution to the development of endothelial dysfunction. Primary human umbilical vein endothelial cells (HUVECs) were used, and multinucleated cells were generated by polyethylene glycol-induced fusion. Cells were incubated under control conditions or exposed to low-density lipoproteins (LDL; 100 µg/mL, 24 h). A comprehensive analysis was performed, including transcriptomic and proteomic (secretome) profiling using gene set enrichment analysis (GSEA), as well as functional assays assessing transendothelial LDL transport, intracellular cholesterol accumulation, macrophage migration, and the expression and secretion of pro-inflammatory cytokines (IL-6, IL-8). MVECs exhibited pronounced differences compared to TECs. GSEA revealed reduced enrichment of pathways related to canonical nuclear factor kappa B (NF-κB) signaling and negative regulation of NF-κB transcription factor activity, actin cytoskeleton organization, focal adhesion assembly, basement membrane organization, and vesicle-mediated transport in MVECs relative to TECs, indicating impaired cytoskeletal integrity, altered cell–matrix interactions, dysregulated inflammatory signaling, and reduced vesicular trafficking activity. Functionally, MVECs demonstrated an increased capacity for cholesterol accumulation and enhanced transendothelial migration of macrophages. Notably, transendothelial LDL transport across the MVEC monolayer was not increased, suggesting a predominance of intracellular lipid accumulation. MVECs also exhibited a pronounced pro-inflammatory phenotype, characterized by elevated expression and secretion of IL-6 and IL-8. Taken together, these findings indicate that MVECs represent a functionally altered endothelial phenotype with impaired barrier function, dysregulated lipid metabolism, and enhanced inflammatory activity. Local accumulation of MVECs within the vascular wall may contribute to the formation of pro-atherogenic regions and play a role in the initiation and progression of endothelial dysfunction. Full article

Voltage-gated ion channels (VGICs) are traditionally associated with electrically excitable cells; however, increasing evidence indicates that they are also expressed in non-excitable cells, including vascular endothelial cells. This review aims to summarize the current knowledge on the expression, regulation, and functional role of VGICs in the vascular endothelium, and to highlight their potential contribution to endothelial signaling. We examined the molecular structure, biophysical properties, and functional roles of voltage-gated Na⁺ (Na_V), Ca²⁺ (Ca_V), and K⁺ (K_V) channels in vascular endothelial cells. Particular attention was given to studies investigating VGIC activity in native endothelium and to emerging mechanisms regulating their activation. Endothelial cells express multiple VGIC subtypes at low densities, which are insufficient to generate action potentials but can modulate membrane potential (V_M) and Ca²⁺-dependent signaling. The dynamic regulation of the endothelial V_M, through the interplay between hyperpolarizing and depolarizing conductances, emerges as a key determinant of VGIC availability and activation. VGICs contribute to essential endothelial functions, including angiogenesis, vasomotor responses, blood–brain barrier permeability, and inflammation. Dysregulated VGIC expression and/or activity may be implicated in several pathological conditions, such as atherosclerosis, calcific aortic stenosis, and tumor vascularization. VGICs represent an unexpected but functionally relevant component of endothelial signaling. Elucidating their role in native vascular beds and disease contexts may uncover novel mechanisms of endothelial regulation and identify new therapeutic targets in cardiovascular and cancer biology. Full article

Atherosclerosis (AS) is the primary underlying cause of cardiovascular and cerebrovascular diseases. The occurrence and development of AS are closely related to lipid deposition, chronic inflammation, phenotypic modulation of vascular smooth muscle cells (VSMCs), and extracellular matrix (ECM) remodeling. Numerous studies indicate that low-density lipoprotein receptor-associated protein 1 (LRP1), as a multifunctional receptor, contributes to vascular homeostasis in AS and vascular remodeling by regulating lipid handling, inflammatory responses, transforming growth factor beta (TGFβ) signaling, and platelet-derived growth factor receptor beta (PDGFRβ) trafficking. Rather than treating the LRP1-TGFβ-PDGFRβ relationship as a fully established linear pathway, this review distinguishes demonstrated mechanisms from inferred cross-talk and proposes an integrated, cell- and stage-dependent regulatory model. This article systematically elaborates on the structure and function of LRP1; LRP1-mediated regulation of TGFβ and PDGFRβ in AS and vascular remodeling; the possible relationship among LRP1, TGFβ, and PDGFRβ; and cell-specific effects in VSMCs, macrophages, endothelial cells, and pericytes. Meanwhile, this article summarizes potential translational strategies such as lipid-lowering, anti-inflammatory therapy, PDGFRβ inhibitor repositioning, TGFβ pathway modulation, biomarker-based stratification, and LRP1-targeted delivery. A deeper understanding of the cell-specificity and stage-dependence of the LRP1-TGFβ-PDGFRβ signaling network may help elucidate the progression mechanism of AS and provide new ideas for risk stratification and precise intervention. Full article

Objective: Restless leg syndrome (RLS) has been associated with an increased risk of vascular disorders, which suggests that endothelial dysfunction plays an important role in the pathogenesis of RLS. In this study, we aimed to evaluate coronary endothelial dysfunction in RLS patients using coronary flow velocity reserve (CFVR) and compared it with healthy controls. Methodology: In this study, the participants were divided into two groups as group RLS (n = 42) and group HC (n = 41). The primary outcome was the CFVR compared between groups. The number of participants with a CFVR value below 2.0 was also evaluated. In addition, a correlation between the international restless legs scale (IRLS) and CFVR, white-blood-cell-count (WBC), and C-reactive protein (CRP) was analyzed. Secondary outcomes were the WBC, hemoglobin, CRP, blood glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and creatinine compared between the two groups. Results: In the group RLS, CFVR was measured lower than healthy controls (p < 0.001). When the groups were compared in terms of the number of participants with a CFVR less than 2.0, the difference between the groups was significant (p < 0.001, 0/41 in group HC and 14/42 in group RLS). Patients with RLS had higher WBC and CRP values. There was a negative correlation between CFVR and IRLS (p < 0.001). The relationship between WBC, CRP, and IRLS was not statistically significant (p = 0.691). Conclusions: In this exploratory study, RLS patients had lower CFVR compared with healthy controls and a negative correlation was observed between RLS severity and CFVR. These findings warrant confirmation in larger, prospectively designed studies with multivariable adjustment. Therefore, we think that it may be beneficial to follow-up patients with RLS in terms of coronary heart disease. Clinical trial number: not applicable. Full article

The myocardium possesses one of the highest vascular densities in the body. The outermost wall layer of large and medium-sized vessels, the adventitia, forms a critical interface between the vasculature and the myocardium and serves as a reservoir for stem and progenitor cells capable of differentiating into all vascular wall lineages as well as innate immune cells, including macrophages. Current cardiac organoid models intrinsically develop networks of endothelial cords and small capillary-like structures that resemble cardiac microvessels. However, these microvessels mostly lack an adventitial compartment in vivo. Here, we present a potential alternative assembloid strategy that combines vascular segments from mouse and human origin with either cardiomyocytes or cardiac spheroids derived from human induced pluripotent stem cells, thereby incorporating large diameter vessels and the vascular adventitia into a cardiac tissue model. Within the assembloids, the myocardial component remained contractile and connected to the vascular adventitia, which displayed cellular sprouting toward the hiPSC-derived cardiac tissue. Immunostaining for vascular and immune markers revealed that the adventitia gave rise to endothelial sprouts and macrophage-like cells which integrated into the myocardial tissue. In summary, we present proof of concept for complex assembloids composed of vessel segments and human iPSC-derived cardiomyocytes which contain and maintain an in vivo-like adventitial compartment. We suggest this model may serve as a platform for investigating myocardial–stromal interactions, cardiac tissue repair, and functional remodeling under both physiological and pathological conditions. Furthermore, the incorporation of large-lumen vessel segments may enable future experimental perfusion, rendering the model particularly suitable for drug testing via intravascular delivery. Full article

In recent years, the study of interleukins (ILs), crucial cytokines involved in inflammation, has garnered significant attention within coronary artery disease including atherosclerosis. This review provides a detailed overview of anti-inflammatory ILs, elucidating their functions within the pathogenesis of atherosclerosis. We examine aspects of all the known anti-inflammatory ILs role in atherosclerosis, the direct impact of these ILs on the inflammation; endothelial, smooth vascular cells and macrophage’s function; and their interactions with signaling pathways and molecules. The potential for diagnostic possibilities and targeted drug therapy to modulate anti-inflammatory ILs activity in atherosclerosis was explored. Taken together, findings from recent studies suggest that the main pathways through which ILs exerts its anti-inflammatory effects are: (1) taking part in the regulation of cholesterol transport or oxidised low-density lipoprotein (oxLDL) phagocytosis (IL-1Ra and IL-36Ra—indirectly); (2) affecting different blood cells’ participation in the inflammation (monocytes, lymphocytes, macrophages); (3) taking place in the remodelation of the arterial wall (affecting smooth muscle and endothelium cells). Overall, IL-35, IL-37, and IL-38 appear to be the most promising for modulation of signaling pathways in experimental works and could be investigated as treatment targets. Recombinant IL-10 is investigated in experimental models as therapeutic tool. IL-1Ra is started being translated into clinical practice already. IL-13 and IL-19 are the least studied. It turns out that anti-inflammatory ILs are unlikely to serve as diagnostic markers for atherosclerosis due to their limited specificity and inconsistent associations with disease progression, as well as insufficient validation in large human cohorts. Moreover, key challenges related to delivery, dosing, and safety remain unresolved. Full article