BackgroundAccelerated atherosclerosis is the leading cause of morbidity and mortality in diabetic patients. Hyperglycemia is a recognized independent risk factor for heightened atherogenesis in diabetes mellitus (DM). However, our understanding of the mechanisms underlying glucose damage to the vasculature remains incomplete.Methodology/Principal FindingsHigh glucose and hyperglycemia reduced upregulation of the NF-κB inhibitory and atheroprotective protein A20 in human coronary endothelial (EC) and smooth muscle cell (SMC) cultures challenged with Tumor Necrosis Factor alpha (TNF), aortae of diabetic mice following Lipopolysaccharide (LPS) injection used as an inflammatory insult and in failed vein-grafts of diabetic patients. Decreased vascular expression of A20 did not relate to defective transcription, as A20 mRNA levels were similar or even higher in EC/SMC cultured in high glucose, in vessels of diabetic C57BL/6 and FBV/N mice, and in failed vein grafts of diabetic patients, when compared to controls. Rather, decreased A20 expression correlated with post-translational O-Glucosamine-N-Acetylation (O-GlcNAcylation) and ubiquitination of A20, targeting it for proteasomal degradation. Restoring A20 levels by inhibiting O-GlcNAcylation, blocking proteasome activity, or overexpressing A20, blocked upregulation of the receptor for advanced glycation end-products (RAGE) and phosphorylation of PKCβII, two prime atherogenic signals triggered by high glucose in EC/SMC. A20 gene transfer to the aortic arch of diabetic ApoE null mice that develop accelerated atherosclerosis, attenuated vascular expression of RAGE and phospho-PKCβII, significantly reducing atherosclerosis.ConclusionsHigh glucose/hyperglycemia regulate vascular A20 expression via O-GlcNAcylation-dependent ubiquitination and proteasomal degradation. This could be key to the pathogenesis of accelerated atherosclerosis in diabetes.

Lyme disease can have cardiac involvement and can subsequently present with various types of atrio ventricular (AV) block. Sinus node dysfunction (SND) and accelerated junctional rhythm are highlighted in this case as an uncommon presentation for Lyme Carditis. This case highlights the importance of having a high index of suspicion for cardiac involvement with Lyme disease when atypical arrhythmias are present.

Multimodality imaging, particularly echocardiography, is paramount in planning and guiding structural heart disease interventions. Transesophageal echocardiography remains unique in its ability to provide real-time 2D and 3D imaging of valvular heart disease and anatomic cardiac defects, which directly impacts the strategy and outcome of these procedures. This review summarizes the role of transesophageal echocardiography in patients undergoing the most common structural heart disease interventions.