The interplay of LDLR, PCSK9, and lncRNA- LASER genes expression in coronary artery disease: Implications for therapeutic interventions

• Published in: Prostaglandins & other lipid mediators Vol. 177; p. 106969
• Main Authors: Ghiasvand, Tayebe, Karimi, Jamshid, Khodadadi, Iraj, Yazdi, Amirhossein, Khazaei, Salman, kichi, Zahra Abedi, Hosseini, Seyed Kianoosh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2025
• Subjects: Aged; Atherosclerosis; Case-Control Studies; Coronary artery disease; Coronary Artery Disease - blood; Coronary Artery Disease - drug therapy; Coronary Artery Disease - genetics; Coronary Artery Disease - metabolism; Female; Gene Expression Regulation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Leukocytes, Mononuclear - metabolism; LncRNA -LASER; Low-density lipoprotein cholesterol; Low-density lipoprotein receptor; Male; Middle Aged; PCSK9; Proprotein Convertase 9 - blood; Proprotein Convertase 9 - genetics; Proprotein Convertase 9 - metabolism; Receptors, LDL - genetics; Receptors, LDL - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; PCSK9; Low-density lipoprotein receptor; Coronary artery disease; LncRNA -LASER; Low-density lipoprotein cholesterol; Atherosclerosis
• DOI: 10.1016/j.prostaglandins.2025.106969
• ISSN: 1098-8823

Coronary artery disease (CAD) is defined as stenosis of coronary arteries due to atherosclerosis. The etiology of atherosclerosis can be attributed to a disruption in lipid metabolism, specifically cholesterol and low-density lipoprotein cholesterol (LDL-C). PCSK9 is an enzyme that controls the metabolism of LDL-C by degrading the low-density lipoprotein receptor (LDLR), which in turn affects the metabolism of LDL-C. A newly discovered Long Non-coding RNA named LASER, which affects the homeostasis of cholesterol, has been identified through the evaluation of bioinformatics. The objective of this study was to assess the levels of gene expression related to cholesterol balance, specifically LDLR, PCSK9, and LASER, in peripheral blood mononuclear cells (PBMCs) of Iranian CAD patients in comparison to controls. This case-control study included 49 CAD patients, with 81.63 % receiving statins, compared to 40 control subjects, of whom 40 % received statins. The qRT-PCR was used to analyze the expression levels of LDLR, PCSK9, and LASER in PBMCs. Additionally, the ELISA method was employed to determine the blood concentration of PCSK9. CAD patients demonstrated a significant reduction in PBMC gene expression levels of LDLR (P < 0.01) and a significant rise in gene expression of PCSK9 and LASER, as well as blood concentration of PCSK9 (P < 0.05) compared to controls. The gene expression of PCSK9 showed a strong positive relationship with LDLR expression in patients (P = 0.0003). Furthermore, a strong correlation was seen between PCSK9 and LASER, as well as LASER and LDLR expression (P < 0.0001) in two groups. PCSK9 and LASER are potential therapeutic targets for atherosclerosis-related disorders, including CAD. Given that patients receiving statins were twice that of the control subjects, and the effect of statins on the LDLR, PCSK9 and LASER, further research is required to delineate the distinct effects of coronary artery disease conditions and statin usage on the expression of the aforementioned genes. [Display omitted] •LDLR, PCSK9, and LASER expression levels were analysed via qRT-PCR.•LDLR gene expression was reduced and PCSK9/LASER gene expression were increased in CAD patients compared to controls.•CAD patients have a positive correlation between PCSK9 and LDLR expression, Unlike controls.•In both groups, a positive and significant relationship between LDLR genes and LASER, as well as PCSK9 and LASER, was observed.