Transfection of Vein Grafts with Early Growth Response Factor-1 Oligodeoxynucleotide Decoy: Effects on Stem-Cell Genes and Toll-like Receptor-Mediated Inflammation

Abstract

The long-term patency of vein grafts is challenged by intimal hyperplasia. We sought to explore the intricate relationships between the transcription factor Egr-1, toll-like receptors (TLRs), and stem cell genes and also assessed oligodeoxynucleotide decoys (ODNs) as a strategy to prevent vein graft failures. A total of 42 New Zealand white rabbits were fed hyperlipidemic chow and classified into three groups. A double-stranded Egr-1 ODN was synthesized and infused in vein grafts prior to anastomosis with the common carotid artery. All vein grafts were retrieved at the conclusion of the predefined experimental period. Real-time quantitative polymerase chain reaction was performed to estimate expression patterns for several genes of interest. MYD88, TLR2-4, TLR8, NF-kB, TNF-α, IFNβ, and IFNγ; chemokines CCL4, CCL20, CCR2; numerous interleukins; and stem cell genes KFL4, NANOG, HOXA5, and HIF1α were universally downregulated in the ODN arm compared with the controls. By understanding these multifaceted interactions, our study offers actionable insights that may pave the way for innovative interventions in vascular reconstructions.

Myocardial Expression of Pluripotency, Longevity, and Proinflammatory Genes in the Context of Hypercholesterolemia and Statin Treatment

“…Consumption of a hypercholesterolemic diet results in notable suppression of the atheroprotective gene HOXA5 in the abdominal aorta [6]. HOXA5 downregulation also correlates with neo-intimal hyperplasia and aberrant angiogenesis [6,9,64]. This facilitates a proatherogenic milieu, characterized by modifications in the extracellular matrix and integrin dynamics, as well as a phenotypic shift in macrophages and VSMCs towards an inflammatory M1 phenotype [43].…”

“…NANOG, a key marker in primordial cellular regulation and pluripotency, has been implicated in vascular pathology by promoting osteopontin expression, VSMC phenotypic changes, cellular proliferation, migration, and survival, as well as by disrupting cell-cell adhesion through VE-cadherin displacement [65][66][67][68]. NANOG upregulation has also been shown to promote neointimal hyperplasia and thoracic aortic atherogenesis [6,9]. Our findings contribute to this body of literature by demonstrating that myocardial NANOG expression is upregulated in response to hyperlipidemic stimuli and is reduced following statin therapy.…”

“…Additional attention is directed towards proatherogenic pluripotency factors such as NANOG and HIF1α [1,[6][7][8]. Dysregulation of their expression has been implicated in various aspects of atherogenesis, including increased release of pro-inflammatory cytokines and chemokines, upregulation of adhesion molecules, migration and phenotypic switching of vascular smooth muscle cells (VSMCs), alterations in extracellular matrix, oxidative stress, and the development of neointimal hyperplasia [6,9,10].…”