DNA modifications in atherosclerosis: from the past to the future.
The role of DNA damage in the pathogenesis of atherosclerosis has been extensively investigated in recent decades. There is now clear that oxidative stress is an important inducer of both DNA damage and telomere attrition which, in turn, can gives rise to genome instability and vascular senescence. This review discusses the role of the DNA damage response, including the key DNA repair pathways (base excision repair, nucleotide excision repair, homologous recombination and non-homologous end joining), deregulated cell cycle and apoptosis in atherosclerosis. We also highlight emerging evidence suggesting that epigenetic changes (DNA methylation and microRNA-mediated mechanisms), not associated with alterations in DNA sequences, may play a critical role in the regulation of the DNA damage response. Nevertheless, further investigation is still required to better understand the complexity of DNA repair and DNA damage response in atherosclerosis, making this topic an exciting and promising field for future investigation. Unraveling these molecular mechanisms provide the rationale for the development of novel efficient therapies to combat the vascular aging process.
CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa, Italy. Electronic address: aborghini@ifc.cnr.it.
Andrea
A
Borghini
Tiziana
T
Cervelli
Alvaro
A
Galli
Maria Grazia
MG
Andreassi
D000818:Animals; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D044127:Epigenesis, Genetic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D016615:Telomere / Q000648:ultrastructure
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D004247:DNA
Atherosclerosis; DNA damage and repair; Environmental contaminants; Epigenetic mechanisms; Telomere shortening