Saxagliptin but Not Sitagliptin Inhibits CaMKII and PKC via DPP9 Inhibition in Cardiomyocytes.

Some oral anti-hyperglycemic drugs, including gliptins that inhibit dipeptidyl peptidase 4 (DPP4), have been linked to the increased risk of heart failure (HF) in type-2 diabetic patients. While the cardiovascular safety trial, TECOS, revealed no link between sitagliptin and the risk of HF, a substantial 27% increase in the hospitalization for HF was observed in type-2 diabetic patients treated with saxagliptin within the SAVOR-TIMI 53 trial. A previous study revealed that saxagliptin impairs the Ca/calmodulin-dependent protein kinase II (CaMKII)-phospholamban (PLB)-sarcoplasmic reticulum Ca-ATPase 2a axis and protein kinase C (PKC) activity in cardiomyocytes leading to impaired cardiac contractility and electrophysiological function.

Association of myeloperoxidase with total and cardiovascular mortality in individuals undergoing coronary angiography--the LURIC study.

Background: The phagocytic enzyme myeloperoxidase (MPO) acts as a front-line defender against microorganisms. However, increased MPO levels have been found to be associated with complex and calcified atherosclerotic lesions and incident cardiovascular disease. Therefore, this study aimed to investigate a predictive role of MPO, a biomarker of inflammation and oxidative stress, for total and cardiovascular mortality in patients referred to coronary angiography.

15-deoxy-Δ¹²,¹⁴-PGJ₂ promotes inflammation and apoptosis in cardiomyocytes via the DP2/MAPK/TNFα axis.

Background: Prostaglandins (PGs), lipid autacoids derived from arachidonic acid, play a pivotal role during inflammation. PGD₂ synthase is abundantly expressed in heart tissue and PGD₂ has recently been found to induce cardiomyocyte apoptosis. PGD₂ is an unstable prostanoid metabolite; therefore the objective of the present study was to elucidate whether its final dehydration product, 15-deoxy-Δ¹²,¹⁴-PGJ₂ (15d-PGJ₂, present at high levels in ischemic myocardium) might cause cardiomyocyte damage.