Effect of statin treatment on metabolites, lipids and prostanoids in patients with Statin Associated Muscle Symptoms (SAMS).

BackgroundBetween 5-10% of patients discontinue statin therapy due to statin-associated adverse reactions, primarily statin associated muscle symptoms (SAMS). The absence of a clear clinical phenotype or of biomarkers poses a challenge for diagnosis and management of SAMS. Similarly, our incomplete understanding of the pathogenesis of SAMS hinders the identification of treatments for SAMS. Metabolomics, the profiling of metabolites in biofluids, cells and tissues is an important tool for biomarker discovery and provides important insight into the origins of symptomatology. In order to better understand the pathophysiology of this common disorder and to identify biomarkers, we undertook comprehensive metabolomic and lipidomic profiling of plasma samples from patients with SAMS who were undergoing statin rechallenge as part of their clinical care.Methods and findingsWe report our findings in 67 patients, 28 with SAMS (cases) and 39 statin-tolerant controls. SAMS patients were studied during statin rechallenge and statin tolerant controls were studied while on statin. Plasma samples were analyzed using untargeted LC-MS metabolomics and lipidomics to detect differences between cases and controls. Differences in lipid species in plasma were observed between cases and controls. These included higher levels of linoleic acid containing phospholipids and lower ether lipids and sphingolipids. Reduced levels of acylcarnitines and altered amino acid profile (tryptophan, tyrosine, proline, arginine, and taurine) were observed in cases relative to controls. Pathway analysis identified significant increase of urea cycle metabolites and arginine and proline metabolites among cases along with downregulation of pathways mediating oxidation of branched chain fatty acids, carnitine synthesis, and transfer of acetyl groups into mitochondria.ConclusionsThe plasma metabolome of patients with SAMS exhibited reduced content of long chain fatty acids and increased levels of linoleic acid (18:2) in phospholipids, altered energy production pathways (β-oxidation, citric acid cycle and urea cycles) as well as reduced levels of carnitine, an essential mediator of mitochondrial energy production. Our findings support the hypothesis that alterations in pro-inflammatory lipids (arachidonic acid pathway) and impaired mitochondrial energy metabolism underlie the muscle symptoms of patients with statin associated muscle symptoms (SAMS)

Root hairs improve root penetration, root-soil contact, and phosphorus acquisition in soils of different strength

Root hairs are a key trait for improving the acquisition of phosphorus (P) by plants. However, it is not known whether root hairs provide significant advantage for plant growth under combined soil stresses, particularly under conditions that are known to restrict root hair initiation or elongation (e.g. compacted or high-strength soils). To investigate this, the root growth and P uptake of root hair genotypes of barley, 'Hordeum vulgare' L. (i.e. genotypes with and without root hairs), were assessed under combinations of P deficiency and high soil strength. Genotypes with root hairs were found to have an advantage for root penetration into high-strength layers relative to root hairless genotypes. In P-deficient soils, despite a 20% reduction in root hair length under high-strength conditions, genotypes with root hairs were also found to have an advantage for P uptake. However, in fertilized soils, root hairs conferred an advantage for P uptake in low-strength soil but not in high-strength soil. Improved root-soil contact, coupled with an increased supply of P to the root, may decrease the value of root hairs for P acquisition in high-strength, high-P soils. Nevertheless, this work demonstrates that root hairs are a valuable trait for plant growth and nutrient acquisition under combined soil stresses. Selecting plants with superior root hair traits is important for improving P uptake efficiency and hence the sustainability of agricultural systems