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Atherosclerosis is a progressive and chronic condition that belongs to the group of Cardiovascular Diseases (CVDs) which represents the first cause of death worldwide. Although recent advances in strategies for studying the mechanisms underlying the disease progression have led to better understanding of the pathological phases, there is still a lot that needs to be done in order to have a complete knowledge of the molecular factors implicated in the pathophysiology of atherosclerosis. In particular, considering the complexity of atherosclerosis, understanding the processes involved in the advancement from early to advanced plaque phenotype, constitutes an essential step towards monitoring the disease progression. Noncoding RNAs, including small noncoding RNAs (miRNAs) and long noncoding RNAs (lncRNAs), have been characterised as important molecules involved in the regulation of physiological cellular processes and the pathology of diseases. MiR-143/145 is a conserved microRNA cluster involved in the maintenance of vascular smooth muscle cells (vSMCs), whose dysregulation can affect the vSMC phenotype. This is one of the key cellular components involved in the pathophysiology of vascular disease, and specifically in atherosclerosis. Studies have shown that the dysregulation of miR-143/145 affects vSMC function during vascular injury and repair, leading to vSMC phenotypical transition towards a pro-pathological state. CARMN is a conserved lncRNA host gene for miR-143/145, whose role was not explored in vSMC phenotypic transition. In this project, CARMN axis role, including CARMN and miR-143/145, was explored in dysregulated vSMC in vitro and in vivo during atherosclerosis. Key findings of this study have shown the downregulation of CARMN and miR-143/145 during the advancement from early to advanced plaque, in both human and mouse atherosclerosis. Functional studies performed in vSMC, identified dysregulated pathways, - following CARMN axis depletion, which were mostly involved in the regulation of vSMC proliferation, migration, inflammation, and lipid homeostasis. In addition, the expression of miR-143/145 was affected following CARMN depletion. In this study, CARMN downregulation was identified as primary regulator of vSMC proliferation independently from the regulation of miR-143/145, whereas the dysregulation of miR-143/145 expression was found involved in the modulation of vSMC migration and de-differentiation towards a macrophage-like phenotype. Herein, CARMN axis role was also explored in an atherosclerotic mouse model of the disease. In particular, the genetic depletion of CARMN, and associated miR-143/145, induced a more advanced plaque phenotype characterised by increased plaque volume and area versus wild type controls. In addition, the knock-out of CARMN enhanced the content of pro-inflammatory cells, increased cell proliferation of cells within the plaque and reduced the collagen content compared to wild type mice. Collectively, this study identified CARMN loss as a detrimental key event occurring in early plaques, which primes vSMC to a dysregulated phenotype in vitro, and leading to more advanced lesions in vivo.