Linas Černiauskas

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with atherosclerosis representing its principal pathological basis. High-density lipoproteins (HDL) and extracellular vesicles (EVs) are abundant circulating particles implicated in lipid metabolism, vascular inflammation, intercellular communication, and thrombotic processes relevant to atherosclerosis. Although HDLs and EVs differ in origin, structure, biogenesis, and canonical function, they share overlapping physicochemical and molecular features. Their density ranges substantially overlap, and small EV populations may approach the upper size range of HDL particles, making their separation from plasma technically challenging. As a result, common isolation workflows may generate HDL-enriched or EV-enriched fractions rather than fully particle-specific preparations, complicating the interpretation of proteomic, lipidomic, nucleic acid, and functional studies. This review compares the structural and biophysical characteristics, biogenesis pathways, molecular cargo, and atherosclerosis-related functions of HDLs and EVs. We highlight how both particle classes contribute to endothelial activation, inflammation, cholesterol handling, foam cell formation, plaque progression, and thrombosis, while also emphasizing their distinct biological roles. Finally, we discuss whether HDL–EV overlap should be interpreted solely as methodological co-isolation or may also reflect biologically relevant interactions within circulating nanoparticle networks in atherosclerosis.

Despite increasing efforts to improve cardiovascular disease (CVD) risk evaluation and management, it remains a leading cause of mortality and morbidity worldwide. This has driven interest in high-density lipoprotein (HDL)-related biomarkers as indicators of oxidative stress and atherogenic processes not fully captured by traditional lipid measurements. In this study, we examined specific paraoxonase 1 (PON1) activity and its relationship with anthropometric, blood pressure, and lipid metabolism measures in 100 middle-aged Lithuanian individuals at high cardiovascular risk. HDL fractions were isolated using iodixanol-based density gradient centrifugation. PON1 concentration and arylesterase activity were measured, and specific activity was defined as arylesterase activity normalized to PON1 concentration. No significant associations were observed between specific PON1 activity and age, body mass index, waist circumference, blood pressure, smoking status, or statin use. Specific PON1 activity was independently associated with lower risk-weighted apolipoprotein B and lower low-density lipoprotein cholesterol levels. These exploratory findings suggest that higher specific PON1 activity may reflect a less atherogenic lipid profile in individuals at high cardiovascular risk, as indicated by its association with LDL-C and with risk-weighted apolipoprotein B. Because direct oxidative stress and inflammatory markers were not measured, interpretations regarding oxidative burden should be considered indirect and hypothesis-generating. Given the cross-sectional nature of the study and the relatively small sample size, these results should be interpreted as exploratory and hypothesis-generating. Further longitudinal studies in larger populations are needed to confirm these observations.

Introduction: High-density lipoprotein (HDL) particles are key participants in reverse cholesterol transport. Cholesterol efflux capacity (CEC) and apolipoprotein A1 (Apo A1) are HDL-related biomarkers often used to evaluate HDL particle functionality and quantity. This study aimed to assess the correlation between CEC and Apo A1 concentrations and explore whether methodological aspects influence the correlation results. Materials and methods: This meta-analysis was prospectively registered in the PROSPERO database (registration number CRD42024552535). Three databases, PubMed, Web of Science, and Cochrane Library, were screened for the studies published between January 2000 and May 2024. The correlation results were analyzed using a random-effects model, and sensitivity and subgroup analyses were performed. Results: A total of 19 studies with 4967 participants were included. This meta-analysis’s results indicated a statistically significant positive moderate strength correlation between CEC and Apo A1 concentrations. A high level of study heterogeneity was observed among the included studies. Further exploration into this heterogeneity revealed that different cell culture lines and cholesterol acceptors used to evaluate CEC impact the overall result of the pooled correlation estimate. The methods used to evaluate Apo A1 did not significantly affect the correlation estimate between CEC and Apo A1 concentrations. Conclusions: The correlation between CEC and Apo A1 lacks strength and consistency for Apo A1 being used as a surrogate marker for HDL function in a clinical setting. Currently, there is a high need for the standardization of CEC measurement methodologies that impact the overall results and comparability of the studies that have already been conducted.

Background and Objectives: Cuticular drusen are a rare form of early-onset drusen maculopathy, which falls within the spectrum of age-related macular degeneration. Previous research suggests that cuticular drusen can result from monogenic inheritance of pathogenic variants in the complement factor H coding CFH gene. These variants impair regulation of the alternative complement pathway, leading to increased central retinal inflammation, progressive tissue damage, and ultimately, vision loss. This study aims to assess the pathogenic potential of the variant NM_000186.4(CFH):c.1318C>T, previously classified as a variant of unknown significance. Materials and Methods: Eight individuals from three generations of a single family underwent ophthalmologic evaluation, including biomicroscopy, ophthalmoscopy, optical coherence tomography, and optical coherence tomography angiography. Subsequently, whole-exome sequencing of the proband‘s DNA sample was performed. Sanger sequencing was used to validate the whole-exome sequencing results and to assess segregation of the identified variant in the family. The individuals’ clinical, instrumental, and genetic data were collected and stored in the database iGENLIT. Results: the heterozygous NM_000186.4(CFH):c.1318C>T variant was detected in six family members. Of these, five have been clinically diagnosed with cuticular drusen. Three affected individuals are currently in their 40s and maintain good visual acuity. In two family members, the drusen progressed to choroidal neovascularization, fibrosis, and atrophy, resulting in profound visual loss at the ages of 54 and 62. One 21-year-old individual also carries the variant, but currently shows no evidence of drusen, likely due to age. Conclusion: In this study, we demonstrated a genotype–phenotype relationship in individuals with the NM_000186.4(CFH):c.1318C>T variant, which suggests its pathogenic role in the development of cuticular drusen and associated complications.

Cardiovascular diseases are the leading cause of mortality worldwide. Since atherosclerosis, an inflammatory, lipid-driven disease, is an underlying basis for the development of cardiovascular disease, it is important to understand its relationship with confounding factors, such as oxidative lipid degradation. In contrast, circulating antioxidants prevent oxidative lipid damage, and therefore, may be associated with reduced development of atherosclerosis. We aimed to assess oxidative lipid degradation biomarker malondialdehyde (MDA) and antioxidant defense system components, total antioxidant capacity (TAC) and superoxide dismutase (SOD) inhibition rate levels, in healthy women and evaluate their relationships with age, anthropometric measures, and lipid metabolism biomarkers. The study included 86 healthy middle-aged women. MDA in human serum samples was evaluated by HPLC, and the TAC and SOD inhibition rates were measured by photometric methods. MDA was found to be associated with age, total cholesterol, non-HDL cholesterol, apolipoprotein B and triacylglycerols. TAC was shown to be associated with age, BMI, and waist circumference, as well as lipid metabolism biomarkers apolipoprotein B and triacylglycerol, while SOD inhibition rate was only associated with total cholesterol, apolipoprotein B and triacylglycerols. In conclusion, the association of oxidative status indices, MDA, TAC and SOD, with cardiovascular risk factors suggests that they could be additional useful biomarkers in the research of aging, obesity, and atherosclerosis pathogenesis.