Role of somatic mutations in vascular disease formation

Abstract

Coronary artery disease, cerebrovascular disease, pulmonary artery hypertension and Alzheimer’s disease all lead to substantial morbidity and mortality, and we currently lack effective treatments for these vascular diseases. Since the discovery, decades ago, that atherosclerotic lesions display clonal growth, atherosclerosis and other vascular diseases have been postulated to be neoplastic processes, arising through a series of critical somatic mutations. There is conflicting evidence supporting this but studies of DNA damage and mutagenesis, both genomic and mitochondrial, in atherosclerotic and vascular lesions, have yielded evidence that somatic mutations are involved in atherogenesis and vascular disease development. The roles of mitochondrial DNA damage, oxidative stress and signaling by members of the TGF-β receptor family are implicated. With the increasing convenience and cost-effectiveness of genome sequencing, it is feasible to continue to seek specific genetic targets in the pathogenesis of these devastating diseases, with the hope of developing personalized genomic medicine in the future.

Keywords::

• atherosclerosis
• human genome project
• mitochondrial DNA
• pulmonary artery hypertension
• somatic mutation

Financial & competing interests disclosure

This work was partially supported by grants (R01HL083471, T32HL083774, and K08HL076345) from the NIH and by the Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.