Targeting Chromatin Remodeling to Prevent Cardiovascular Disease in Diabetes

Title:Targeting Chromatin Remodeling to Prevent Cardiovascular Disease in Diabetes

Volume: 16 Issue: 6

Author(s): Sarah Costantino, Francesco Paneni and Francesco Cosentino

Affiliation:

Keywords: Cardiovascular disease, chromatin modifying agents, diabetes, metabolic memory epigenetics, pharmacological reprogramming.

Abstract: Diabetes is a major cause of cardiovascular morbidity and mortality and its prevalence is rapidly increasing worldwide. Despite clear advances in developing effective glucose-lowering drugs, clinical trials have recently shown that intensive glycemic control failed to reduce cardiovascular events in the diabetic population. These findings support the concept that the hyperglycemic environment may be remembered in the cardiovascular system. This phenomenon has been recently defined as “metabolic memory” and may contribute to explain the progression of diabetic vascular complications despite achievement of target HbA_1c levels. In this regard, epigenetic changes of DNA/histone complexes are emerging as important modulators of oxidant and inflammatory genes, thus leading to persistent cardiac and vascular dysfunction. Over the last few years, the rapid development of many compounds (i.e. histone deacetylase and histone acetyltransferase inhibitors) able to erase adverse chromatin signatures led to the perception that reverting hyperglycemic damage might be possible and represents an attractive challenge. Here we critically discuss recent evidence supporting the concept that chromatin alterations are key drivers of cardiovascular disease and describe the emerging potential of chromatin modifying agents for the reprogramming of detrimental epigenetic signatures in patients with cardiometabolic disturbances.

Cite this article as:

Costantino Sarah, Paneni Francesco and Cosentino Francesco, Targeting Chromatin Remodeling to Prevent Cardiovascular Disease in Diabetes, Current Pharmaceutical Biotechnology 2015; 16 (6) . https://dx.doi.org/10.2174/138920101606150407113644