Interindividual variabilities between patients taking the anticoagulant rivaroxaban are a result of hepatic metabolism by CYP 450 enzymes. The objective of this study was to evaluate the impact of rivaroxaban on CYP4F2 and transcription factors’ activity in HUVECs. Rivaroxaban and its metabolites were detected by UPLC-ESI-MS and UPLC-QTOF-MS. CYP4F2, HNF4α, PXR and CAR expressions were determined in HUVECs by qPCR; CYP4F2 protein concentration was determined by ELISA. Rivaroxaban metabolites (M-1, M-2, M-5, M-8, M-10, M-11 and M-18) were detected in endothelial cells’ culture medium. Increasing concentrations of rivaroxaban determined lower 13-docosenamide concentrations. Rivaroxaban and dexamethasone reduced the expression of CYP4F2 when hsa-miR-24-3p—both CYP4F2 expression and CYP4F2 protein levels in HUVECs. The expression of the transcription factors HNF4α, PXR and CAR was not detected in HUVECs.

Background: Ischemic heart disease (IHD) is the most prevalent type of cardiovascular disease. The main cause of IHD is atherosclerosis, which is a multifactorial inflammatory disease of blood vessels. Studies show that bacteria might have a significant impact on the pathogenesis of atherosclerosis and plaque rupture. This study aimed to evaluate the complexity of interactions between bacteria and the human body concerning metabolites and bacterial genes in patients with ischemic heart disease. Methods: Bacterial 16S rDNA and wcaF, papC, and sdhC genes were detected in whole blood using a real-time PCR methodology. An enzyme-linked immunosorbent assay was used to measure the concentration of the LL-37 protein. An analysis of ARA in blood plasma was performed. Results: Bacterial 16S rDNA was detected in 31% of the study patients, and the genes wcaF and sdhC in 20%. Enterobacterales genes were detected more frequently in patients younger than 65 years than in patients aged 65 years and older (p = 0.018) and in patients with type 2 diabetes (p = 0.048). Concentrations of the human antimicrobial peptide LL-37 and 12S-HETE concentrations were determined to be higher if patients had 16S rDNA and biofilm-specific genes. Conclusions: The results of this study enhance the understanding that Enterobacterales bacteria may participate in the pathogenesis of atherosclerosis and IHD. Bacterial DNA and host metabolites in higher concentrations appear to be detected.

Background: Ischemic heart disease remains the leading cause of death worldwide, with coronary microvascular dysfunction (CMD) as a key complication after ST-elevation myocardial infarction (STEMI). Endothelial dysfunction contributes to CMD, impairing vascular tone and increasing inflammation. While angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) aid vascular health, their efficacy may improve with therapeutic ultrasound, which enhances drug delivery and endothelial response. This study explores the combined effects of ultrasound and pharmacological treatment on the ACE axis and inflammation in endothelial and renal cells. Methods: Human umbilical vein endothelial cells (HUVECs) and human renal proximal tubular epithelial cell line RPTEC/TERT1 were treated with captopril, losartan, and dexamethasone, alone or combined with low-frequency ultrasound (LFU). Cell viability and wound-healing assays assessed cellular function, while nitric oxide (NO) and reactive oxygen species (ROS) assays were used to evaluate redox signaling. Gene expression related to the ACE axis, inflammation, and vascular and renal cell function was analyzed via qPCR. Results: Captopril and losartan combined with LFU improved endothelial cell viability, wound healing, and NO production at various concentrations, whereas only losartan with LFU enhanced cell viability and wound healing in renal cells. Dexamethasone with LFU increased ROS levels and had variable effects on RPTEC/TERT1 cell survival. Gene expression analysis showed that LFU alone reduced pro-inflammatory markers VCAM-1, ICAM-1, and PTGS2 in captopril-treated HUVECs and similarly affected CYP4F2 in losartan-treated HUVECs. LFU also decreased PTGS2 expression at higher dexamethasone concentrations. In RPTEC/TERT1 cells, LFU alone did not impact SGLT2 or GGT1 expression, but captopril with LFU downregulated GGT1, and dexamethasone with LFU upregulated SGLT2 at higher concentrations. Conclusions: This study demonstrates that LFU enhances the effects of RAS inhibitors by promoting NO synthesis and reducing oxidative stress, while its combination with dexamethasone may have variable, potentially cytotoxic effects on renal cells. Gene expression patterns suggest LFU’s anti-inflammatory potential and its role in modulating drug efficacy.

Background and Objectives: This study aimed to determine the diagnostic yield of familial hypercholesterolemia (FH) genotyping and to describe the clinical phenotype and pharmacogenomic (PGx) implementation readiness of adults referred for clinically suspected FH at a Lithuanian tertiary cardiology center. The study was designed as a descriptive retrospective analysis of existing clinical and genetic test results generated using heterogeneous historical sequencing platforms. Materials and Methods: This single-center descriptive cohort included 48 adults with clinically suspected FH evaluated between February 2022 and June 2023. Patients were classified according to Dutch Lipid Clinic Network criteria before genetic testing. Historical targeted next-generation sequencing (NGS) and whole-exome sequencing (WES) results were reviewed. Genetic findings were interpreted using a three-tier reporting framework: diagnostic FH-associated findings, pharmacogenomic findings relevant to future implementation, and VUS, common polymorphisms, or other non-diagnostic findings. Because harmonized PGx star-allele/diplotype calling was not available across historical platforms, PGx findings were not analysed as a mutually exclusive patient-level category. Results: Pathogenic FH-associated variants were identified in 13 of 48 patients (27.1%), including eight LDLR and five APOB variant carriers. In the remaining 35 patients (72.9%), no pathogenic or likely pathogenic FH-associated variant was identified within the analytical scope of the historical test used. This non-diagnostic category could include VUS, common polymorphisms, exploratory findings, or no reportable variant. Patients carrying pathogenic LDLR variants had higher total cholesterol and LDL-C concentrations than patients without detected pathogenic variants. PGx-related findings were considered observations relevant to reporting and future implementation; they were not evaluated as predictors of statin response, statin intolerance, or LDL-C reduction. Conclusions: In this Lithuanian real-world cohort, pathogenic LDLR or APOB variants were identified in 27.1% of patients referred for suspected FH. Retrospective analyses of heterogeneous historical genetic results can inform diagnostic reporting and implementation planning but cannot establish PGx associations with statin efficacy or intolerance without harmonized diplotype calling and prospectively collected treatment outcomes.