J Physiol
Department of Medicine, Division of Cardiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Published: February 2023
Microvascular dysfunction predicts adverse cardiovascular events despite absence of large vessel disease. A shift in the mediator of flow-mediated dilatation (FMD) from nitric oxide (NO) to mitochondrial-derived hydrogen peroxide (H O ) occurs in arterioles from patients with coronary artery disease (CAD). The underlying mechanisms governing this shift are not completely defined. Lipid phosphate phosphatase 3 (LPP3) is a transmembrane protein that dephosphorylates lysophosphatidic acid, a bioactive lipid, causing a receptor-mediated increase in reactive oxygen species. A single nucleotide loss-of-function polymorphism in the gene coding for LPP3 (rs17114036) is associated with elevated risk for CAD, independent of traditional risk factors. LPP3 is suppressed by miR-92a, which is elevated in the circulation of patients with CAD. Repression of LPP3 increases vascular inflammation and atherosclerosis in animal models. We investigated the role of LPP3 and miR-92a as a mechanism for microvascular dysfunction in CAD. We hypothesized that modulation of LPP3 is critically involved in the disease-associated shift in mediator of FMD. LPP3 protein expression was reduced in left ventricle tissue from CAD relative to non-CAD patients (P = 0.004), with mRNA expression unchanged (P = 0.96). Reducing LPP3 expression (non-CAD) caused a shift from NO to H O (% maximal dilatation: Control 78.1 ± 11.4% vs. Peg-Cat 30.0 ± 11.2%; P < 0.0001). miR-92a is elevated in CAD arterioles (fold change: 1.9 ± 0.01 P = 0.04), while inhibition of miR-92a restored NO-mediated FMD (CAD), and enhancing miR-92a expression (non-CAD) elicited H O -mediated dilatation (P < 0.0001). Our data suggests LPP3 is crucial in the disease-associated switch in the mediator of FMD. KEY POINTS: Lipid phosphate phosphatase 3 (LPP3) expression is reduced in heart tissue patients with coronary artery disease (CAD). Loss of LPP3 in CAD is associated with an increase in the LPP3 inhibitor, miR-92a. Inhibition of LPP3 in the microvasculature of healthy patients mimics the CAD flow-mediated dilatation (FMD) phenotype. Inhibition of miR-92a restores nitric oxide-mediated FMD in the microvasculature of CAD patients.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10979460 | PMC |
http://dx.doi.org/10.1113/JP283923 | DOI Listing |
J Sci Food Agric
January 2025
College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China.
Background: Dietary supplementation for beef cattle, using natural plant extracts, such as oregano essential oil (OEO), has proven effective in enhancing growth performance, beef production quantity and quality, and ensuring food safety. However, the precise mechanisms underlying these effects remain unclear. This study investigated the impact of OEO on carcass traits, muscle fiber structure, meat quality, oxidative status, flavor compounds, and gene regulatory mechanisms in the longissimus thoracis (LT) muscles of beef cattle.
View Article and Find Full Text PDFIntensive Care Med Exp
January 2025
Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, O&N1 Box 503, 3000, Louvain, Belgium.
Background: Sepsis-induced cardiomyopathy (SICM) often occurs in the acute phase of sepsis and is associated with increased mortality due to cardiac dysfunction. The pathogenesis remains poorly understood, and no specific treatments are available. Although SICM is considered reversible, emerging evidence suggests potential long-term sequelae.
View Article and Find Full Text PDFCurr Microbiol
January 2025
Institute of Agricultural Environmental Resources, Yunnan Academy of Agricultural Sciences, Kunming, 650205, People's Republic of China.
A novel phosphate-solubilizing and zinc-solubilizing actinobacterium strain YIM S08009 was isolated from rhizosphere soil collected from Pinus yunnanensis in Wuliangshan National Nature Reserve, Pu'er City, Yunnan Province, southwest PR China. Cells of strain YIM S08009 were Gram-stain-positive, non-motile, irregular rods to cocci, and formed yellow and white colonies on nutrient agar. Growth was observed at 10-40 °C (optimum 25-35 °C), pH 6.
View Article and Find Full Text PDFNat Commun
January 2025
Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
School of Tropical Agriculture and Forestry & Sanya Institute Breeding and Multiplication, Hainan University, Haikou/Sanya 570228/572025, China.
Stylo () exhibits excellent tolerance to low-phosphate (Pi) availability, but the underlying mechanisms responsible for improving the phosphorus (P) utilization efficiency (PUE) remain unclear. This study employed metabolomics, lipidomics, and gene expression analyses to investigate the differential responses to low-Pi stress between the high-PUE genotype CF047827 and the cultivar Reyan No. 2.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!
© LitMetric 2025. All rights reserved.