Development of heart failure (HF) after myocardial infarction (MI) is responsible for premature death. Complex cellular and molecular mechanisms are involved in this process. A number of studies have linked the epitranscriptomic RNA modification N6-methyladenosine (m6A) with HF, but it remains unknown how m6A affects the risk of developing HF after MI. We addressed the regulation of m6A and its demethylase fat mass and obesity-associated (FTO) after MI and their association with HF. Using liquid chromatography coupled to mass spectrometry, we observed an increase of m6A content in the infarcted area of rat hearts subjected to coronary ligation and a decrease in blood. FTO expression measured by quantitative PCR was downregulated in the infarcted hearts. In whole blood samples collected at the time of reperfusion in MI patients, m6A content was lower in patients who developed HF as attested by a 4-month ejection fraction (EF) of ≤40% as compared to patients who did not develop HF (EF > 50%). M6A content was higher in females. These results show that m6A measured in blood is associated with HF development after MI and motivate further investigation of the potential role of m6A as a novel epitranscriptomics biomarker and therapeutic target of HF.

Background/Objectives: Cardiovascular disease (CVD) remains the leading cause of death worldwide and requires a deeper understanding of its pathogenesis for effective prevention and treatment. Familial hypercholesterolemia (FH), characterized by high levels of LDL cholesterol, is a significant risk factor for CVD. FH background remains unexplained despite advances in genetic testing. The aim was identification early changes in the plasma lipidome of individuals at high cardiovascular risk (HCVR) using liquid chromatography coupled with mass spectrometry. Methods: The lipidomic analysis examined over 400 compounds. Twenty individuals with suspected FH, very high cardiovascular risk (VHCVR), and undetectable mutations in the LDLR, APOB, or PCSK9 genes were compared to control group in a qualitative-quantitative analysis. Results: Multivariate analyses revealed statistically significant alterations in glycerophospholipids (GC), with a notable increase in phosphatidylcholines ((O-36:0/16:0), OR (95% CI): 1.246 (1.042–1.490), p = 0.0157), phosphatidylethanolamines ((O-40:7/22:6), OR (95% CI): 1.119 (1.039–1.205), p = 0.0028), and phosphatidylglycerol ((40:8/20:4), OR (95% CI): 1.053 (1.008–1.101), p = 0.0219) only in patients with HCVR. These changes, particularly in major classes of GC, underscored their potential as biomarkers for early assessment of cardiovascular risk. Lipidomic profiling revealed associations between specific lipid species and the comorbidities of arterial hypertension, atherosclerosis, and insulin resistance, implicating their role in atherosclerotic cardiovascular disease (ASCVD). Conclusions: This study points early changes in the plasma lipidome in individuals at HCVR, underline potential biomarkers, therapeutic targets for ASCVD, and offer opportunities to improve ASCVD diagnosis, therapy, and risk management strategies through detailed personalized medical approach.

Background/Objectives: Having serum biomarkers available for cardiac transthyretin amyloidosis (ATTR-CA) would be beneficial for diagnosis and prognosis. This study aimed to identify potential ATTR-CA biomarkers through proteomic analysis. Patients and Methods: Serum proteomic analyses were conducted on 15 ATTR-CA patients before receiving treatment, 11 ATTR-CA patients who had received tafamidis treatment for at least six months, and 13 patients with suspected cardiac amyloidosis who were later ruled out. All patients underwent blood tests, standard 12-lead electrocardiography, transthoracic echocardiography, and ^99mTc-DPD scintigraphy. Results: Proteomic analysis revealed significant differences in protein levels among the study groups. Key findings revealed increased levels of several proteins, including ceruloplasmin, apolipoprotein E, SERPINA1, and cDNA FLJ54111 (which is highly similar to serum transferrin), in ATTR-CA patients before receiving specific treatment. There was also a reduction in prothrombin, transferrin, CD14, and alpha-2-macroglobulin. In the ATTR-CA group treated with tafamidis, elevated levels of SERPINA1, paraoxonase 1, and complement C2 were observed. Notably, levels of cDNA FLJ54111 and SERPINA3 were reduced in this group. Compared to the control group, patients with ATTR-CA exhibited higher levels of ceruloplasmin, SERPINA3, and VCAM1, as well as lower levels of ApoA-I, ApoA-II, clusterin, and gelsolin. Controls exhibited elevated levels of transthyretin and prothrombin. Conclusions: This study identified candidate serum biomarkers for diagnosing ATTR-CA and monitoring the effectiveness of tafamidis treatment.

Familial hypercholesterolemia (FH) is caused by an impaired ability to clear circulating low-density lipoprotein (LDL-C) particles due to a defective low-density lipoprotein receptor (LDLR). FH significantly increases cardiovascular risk (CVR). Although conventional lipid parameters are essential for diagnosing FH, they do not fully capture the metabolic impact of inherited LDLR dysfunction. This study aimed to characterize the plasma lipidomic phenotype associated with pathogenic LDLR variants in individuals with suspected FH. Forty-four participants underwent genetic testing for LDLR, apolipoprotein B-100 (APOB), and protein convertase subtilisin/kexin type 9 (PCSK9). After excluding three carriers of the APOB p.Arg3527Gln variant, the comparative lipidomic analysis included 41 participants. The study included 17 carriers of pathogenic LDLR variants and 24 participants without a detected pathogenic variant in the tested panel. We performed plasma lipidomic profiling using flow-injection analysis coupled with high-resolution tandem mass spectrometry (FIA-MS/MSALL) without chromatographic separation. Lipid annotation and data processing were performed using LipidView software, and lipidomic measurements were expressed as relative signal abundances derived from mass spectrometry (MS) peak intensities. Statistical analyses included Mann–Whitney U tests with false discovery rate (FDR) correction across the analyzed lipid features. Exploratory multivariable logistic regression and receiver operating characteristic (ROC) analyses were also performed. There were no differences in conventional lipid parameters between genetically confirmed LDLR variant carriers and participants without a detected pathogenic variant in the tested panel. At the nominal level (unadjusted p < 0.05), lipidomic profiling revealed differences in glycerophospholipid (GP) related analytical features between groups. However, no individual lipid feature remained statistically significant after full-family FDR correction. Among (GPs), 69 feature records (16.3%) showed nominal between-group differences, predominantly lower abundance in LDLR variant carriers. The most consistent nominal alterations were observed in features annotated as phosphatidylinositol triphosphates (PIP3) and N-acyl phosphatidylethanolamines (NAPE). Among the analyzed fatty acyls (FAs), 72.7% showed nominally lower relative abundance in LDLR variant carriers. We used exploratory multivariable models to identify GP and FA-related features associated with the detected pathogenic LDLR variant status. The models showed within-cohort discrimination. However, these models were developed and evaluated in the same small cohort after data-driven variable selection. They were not externally validated. Therefore, the findings should be interpreted as hypothesis-generating and do not establish diagnostic performance, clinical utility, or functional pathway impairment. Further validation in larger cohorts using targeted lipidomics with chromatographic separation is necessary.