11 research outputs found
The comprehensive effects of hyperlipidemia and hyperhomocysteinemia on pathogenesis of atherosclerosis and DNA hypomethylation in ApoE-/- mice
Pathway-Guided Deep Neural Network toward Interpretable and Predictive Modeling of Drug Sensitivity
Association between blood pressure and DNA methylation of retrotransposons and pro-inflammatory genes
Effects of homocysteine on adipocyte differentiation and CD36 gene expression in 3T3-L1 adipocytes
Folic acid inhibits tau phosphorylation through regulation of PP2A methylation in SH-SY5Y cells
Relationship between plasma homocysteine level and lipid profiles in a community-based Chinese population
PPAR alpha: an emerging therapeutic target in diabetic microvascular damage
The global pandemic of diabetes mellitus portends an alarming rise in the prevalence of microvascular complications, despite advanced therapies for hyperglycemia, hypertension and dyslipidemia. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is expressed in organs affected by diabetic microvascular disease (retina, kidney and nerves), and its expression is regulated specifically in these tissues. Experimental evidence suggests that PPAR alpha activation attenuates or inhibits several mediators of vascular damage, including lipotoxicity, inflammation, reactive oxygen species generation, endothelial dysfunction, angiogenesis and thrombosis, and thus might influence intracellular signaling pathways that lead to microvascular complications. PPAR alpha has emerged as a novel target to prevent microvascular disease, via both its lipid-related and lipid-unrelated actions. Despite strong experimental evidence of the potential benefits of PPAR alpha agonists in the prevention of vascular damage, the evidence from clinical studies in patients with diabetes mellitus remains limited. Promising findings from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study on microvascular outcomes are countered by elevations in participants' homocysteine and creatinine levels that might potentially attenuate the benefits of PPAR alpha activation. This Review focuses on the role of PPAR alpha activation in diabetic microvascular disease and highlights the available experimental and clinical evidence from studies of PPAR alpha agonists