Advanced glycation endproducts and plaque instability: a link beyond diabetes

Abstract

This editorial refers to ‘Higher levels of advanced glycation endproducts in human carotid atherosclerotic plaques are associated with a rupture-prone phenotype’[†][1], by N.M.J. Hanssen et al. , on page 1137 Despite clear advances in the treatment of vascular disease, we are still far from the understanding and valid assessment of the natural history of atherosclerotic plaque. Several studies have shown that the vulnerable plaque is the main culprit for ischaemic cardiac and cerebral events, but reliable indicators of plaque instability remain elusive in clinical practice.1 This aspect deserves attention since rupture of carotid plaques explains at least 15–20% of all ischaemic strokes or transient ischaemic attacks.2 Over 15 million people per year suffer strokes worldwide, resulting in 5 million deaths, and an additional 5 million remain permanently disabled.2 Treatment of carotid artery stenosis by endoarterectomy or stenting can significantly reduce stroke risk, but it is also accompanied by surgery-related morbidity and mortality.1,2 Moreover, not all carotid artery plaques become symptomatic and result in ischaemic events. In this perspective, the identification of carotid plaques at high risk for neurological events is fundamental to the selection of patients for vascular interventions. Different processes involved in the progression of atherosclerotic lesions have been associated with plaque vulnerability.3 Previous seminal investigations have clearly shown that inflammation, proteolysis, and apoptosis are major drivers of plaque complexity and fragility.3 Pathological features of unstable plaques are represented by an atheromatous thin fibrous cap, large necrotic core, infiltration of inflammatory cells, and scarce calcification. Despite available imaging techniques providing an exhaustive macroscopic characterization of the plaque, the inner mechanisms involved remain to be largely elucidated and characterization of the molecular processes is achieved only at post-operative or post-mortem examination.1 The assessment of early markers of plaque vulnerability is an attractive … [1]: #fn-2