cGMP in atherosclerosis: genetic and mechanistic insights

Ischemic heart disease is the leading cause of death worldwide. In addition to traditional risk factors as hypertension or hypercholesterolemia, a positive family history increases the risk to suffer from coronary artery disease and myocardial infarction. Among the common variants which are responsible for this observation and which were identified in the past 20 years, several variants are located at gene loci that harbor genes involved in nitric oxide-cGMP signaling. Here, we discuss novel genetic and mechanistic insights regarding the role of cGMP in atherosclerosis. We investigate the role of platelet cGMP in atherosclerosis and possible therapeutic implications. Furthermore, we provide evidence for a role of phosphodiesterase 5A in atherosclerosis based on private mutations and common genetic variation. Finally, we will discuss phenotypic consequences of altered nitric oxide-cGMP signaling in coronary artery disease using phenome-wide analyses.