Role of advanced glycation end products in hypertension and cardiovascular risk: human studies

Reactive derivatives of nonenzymatic glucose-protein condensation reactions, as well as lipids and nucleic acids exposed to reducing sugars, form a heterogeneous group of irreversible adducts called "advanced glycation endproducts" (AGEs). Numerous studies have investigated the role of the AGEs in diabetic subjects; however, the role on hypertension and the cardiovascular system has been less intensively investigated in clinical studies. This review summarizes clinical data on AGEs and its action on the receptor of AGEs (RAGE) with respect to blood pressure and vascular disease to update the clinician on this important pathway. In summary, clinical data on the AGE-RAGE axis at the moment does not provide evidence for a role in hypertension but for vascular disease, including macrocirculation as well as microcirculation. Potential causes, such as local deposition or signaling pathways are discussed in context with the literature. Finally, the small number of interventional studies is summarized, pointing to a need for more interventional trials with respect to AGEs and vascular disease. Animal data are explicitly excluded to strengthen the clinical focus and to increase the relevance for clinicians.