Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease.
Francisco Rodríguez-EsparragónLaura B Torres-MataSara E Cazorla-RiveroJaime A Serna GómezJesús M González MartínÁngeles Cánovas-MolinaJosé A Medina-SuárezAyose N González-HernándezLidia Estupiñán-QuintanaMaría C Bartolomé-DuránJose Carlos Rodriguez-PerezBernardino Clavo VarasPublished in: International journal of molecular sciences (2023)
ANRIL (Antisense Noncoding RNA in the INK4 Locus), also named CDKN2B-AS1, is a long non-coding RNA with outstanding functions that regulates genes involved in atherosclerosis development. ANRIL genotypes and the expression of linear and circular isoforms have been associated with coronary artery disease (CAD). The CDKN2A and the CDKN2B genes at the CDKN2A/B locus encode the Cyclin-Dependent Kinase inhibitor protein (CDKI) p16INK4a and the p53 regulatory protein p14ARF, which are involved in cell cycle regulation, aging, senescence, and apoptosis. Abnormal ANRIL expression regulates vascular endothelial growth factor (VEGF) gene expression, and upregulated Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis by activating the NF-κB signaling pathway. Here, we explored associations between determinations of the linear, circular, and linear-to-circular ANRIL gene expression ratio, CDKN2A, VEGF and its receptor kinase insert domain-containing receptor (KDR) and cardiovascular risk factors and all-cause mortality in high-risk coronary patients before they undergo coronary artery bypass grafting surgery (CABG). We found that the expression of ANRIL isoforms may help in the prediction of CAD outcomes. Linear isoforms were correlated with a worse cardiovascular risk profile while the expression of circular isoforms of ANRIL correlated with a decrease in oxidative stress. However, the determination of the linear versus circular ratio of ANRIL did not report additional information to that determined by the evaluation of individual isoforms. Although the expressions of the VEFG and KDR genes correlated with a decrease in oxidative stress, in binary logistic regression analysis it was observed that only the expression of linear isoforms of ANRIL and VEGF significantly contributed to the prediction of the number of surgical revascularizations.
Keyphrases
- vascular endothelial growth factor
- coronary artery disease
- poor prognosis
- coronary artery bypass grafting
- long non coding rna
- oxidative stress
- endothelial cells
- gene expression
- cell cycle
- signaling pathway
- binding protein
- cardiovascular risk factors
- percutaneous coronary intervention
- dna methylation
- genome wide
- cardiovascular events
- dna damage
- cell proliferation
- coronary artery bypass
- end stage renal disease
- cardiovascular disease
- chronic kidney disease
- adipose tissue
- ejection fraction
- minimally invasive
- healthcare
- high resolution
- coronary artery
- endoplasmic reticulum stress
- mass spectrometry
- ionic liquid
- transcatheter aortic valve replacement
- lps induced
- insulin resistance
- prognostic factors
- toll like receptor
- diabetic rats
- social media
- immune response
- ischemia reperfusion injury
- drug induced
- epithelial mesenchymal transition
- heat stress
- cell cycle arrest