Diabetes and Its Cardiovascular Complications: Potential Role of the Acetyltransferase p300

Abstract

Diabetes has been shown to accelerate vascular senescence, which is associated with chronic inflammation and oxidative stress, both implicated in the development of endothelial dysfunction. This condition represents the initial alteration linking diabetes to related cardiovascular (CV) complications. Recently, it has been hypothesised that the acetyltransferase, p300, may contribute to establishing an early vascular senescent phenotype, playing a relevant role in diabetes-associated inflammation and oxidative stress, which drive endothelial dysfunction. Specifically, p300 can modulate vascular inflammation through epigenetic mechanisms and transcription factors acetylation. Indeed, it regulates the inflammatory pathway by interacting with nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) or by inducing its acetylation, suggesting a crucial role of p300 as a bridge between NF-κB p65 and the transcriptional machinery. Additionally, p300-mediated epigenetic modifications could be upstream of the activation of inflammatory cytokines, and they may induce oxidative stress by affecting the production of reactive oxygen species (ROS). Because several in vitro and in vivo studies shed light on the potential use of acetyltransferase inhibitors, a better understanding of the mechanisms underlying the role of p300 in diabetic vascular dysfunction could help in finding new strategies for the clinical management of CV diseases related to diabetes.

Latent inter-organ mechanism of idiopathic pulmonary fibrosis unveiled by a generative computational approach

“…3). Moreover, other IPF-related diseases found in this study such as Alzheimer's disease, obesity, cardiovascular diseases, systemic lupus erythematosus are linked to diabetes [35][36][37][38][39] . Furthermore, the two signaling nodes in the inter-organ mechanism of IPF proposed in our study (Fig.…”

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“…One key epigenetic modification in NASH is the acetylation of histone proteins, particularly influenced by enzymes like p300, a histone acetyltransferase [ [8] , [9] , [10] ]. The activity of p300 alters the structure of chromatin, influencing the accessibility of transcription factors to DNA and thereby regulating the transcription of numerous genes involved in lipid metabolism, inflammation, and fibrosis, which are the core features of NASH [ [13] , [14] , [15] ].…”

“…Within the family of histone acetyltransferases, p300 plays a pivotal role in multiple cellular processes, including apoptosis, proliferation, and differentiation, by regulating histone acetylation-dependent chromatin compactness and accessibility [ 8 ]. Lines of evidence suggests that abnormal p300 expression contributes to the pathophysiology of cancers [ 8 ], cognitive and neurodegenerative diseases [ 9 ], and cardiovascular diseases [ 10 ]. Recently, we demonstrated that the administration of garcinol, a natural p300 inhibitor, can ameliorate cisplatin-evoked nephrotoxicity in mice by effectively restraining oxidative stress, inflammation, and apoptosis [ 11 ].…”

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