Publications by authors named "Luisa Rubinelli"
Background: Growing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in atherosclerosis.
View Article and Find Full Text PDFDisruption of sphingolipid homeostasis and signaling has been implicated in diabetes, cancer, cardiometabolic, and neurodegenerative disorders. Yet, mechanisms governing cellular sensing and regulation of sphingolipid homeostasis remain largely unknown. In yeast, serine palmitoyltransferase, catalyzing the first and rate-limiting step of sphingolipid de novo biosynthesis, is negatively regulated by Orm1 and 2.
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- The study investigates the role of the sphingolipid ceramide in heart failure, focusing on the protein Nogo-A's impact on sphingolipid metabolism in heart cells under stress.
- It finds that Nogo-A negatively regulates the enzyme SPT, crucial for ceramide production, thereby reducing ceramide accumulation during stress, which could otherwise lead to harmful heart changes.
- Ultimately, the research concludes that Nogo-A helps maintain heart health by preserving important cellular functions, preventing the development of heart failure in stressful conditions.
Background Most of the circulating sphingosine-1-phosphate (S1P) is bound to ApoM (apolipoprotein M) of high-density lipoprotein (HDL) and mediates many beneficial effects of HDL on the vasculature via G protein-coupled S1P receptors. HDL-bound S1P is decreased in atherosclerosis, myocardial infarction, and diabetes mellitus. In addition to being the target, the endothelium is a source of S1P, which is transported outside of the cells by Spinster-2, contributing to circulating S1P as well as to local signaling.
View Article and Find Full Text PDFCeramides are sphingolipids that modulate a variety of cellular processes via 2 major mechanisms: functioning as second messengers and regulating membrane biophysical properties, particularly lipid rafts, important signaling platforms. Altered sphingolipid levels have been implicated in many cardiovascular diseases, including hypertension, atherosclerosis, and diabetes mellitus-related conditions; however, molecular mechanisms by which ceramides impact endothelial functions remain poorly understood. In this regard, we generated mice defective of endothelial sphingolipid de novo biosynthesis by deleting the Sptlc2 (long chain subunit 2 of serine palmitoyltransferase)-the first enzyme of the pathway.
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- Hypercholesterolemia and hypertension significantly contribute to coronary artery diseases, a leading cause of death in industrialized nations.
- Current animal models fail to effectively mimic human coronary issues, but recent research using ApoE-/- mice shows that high-pressure exposure can induce relevant coronary lesions.
- The study finds that after transverse aortic constriction (TAC), most ApoE-/- mice develop coronary lesions, with many experiencing myocardial events like thrombosis, offering a promising model for studying coronary diseases similar to those in humans.