Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Del, Gaudio, I; Rubinelli, L; Sasset, L; Wadsack, C; Hla, T; Di, Lorenzo, A.
Endothelial Spns2 and ApoM Regulation of Vascular Tone and Hypertension Via Sphingosine-1-Phosphate.
J Am Heart Assoc. 2021; 10(14): e021261
Doi: 10.1161/JAHA.121.021261
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- Führende Autor*innen der Med Uni Graz
- Del Gaudio Ilaria
- Co-Autor*innen der Med Uni Graz
- Wadsack Christian
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- Abstract:
- 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. Mice lacking endothelial S1P receptor 1 are hypertensive, suggesting a vasculoprotective role of S1P signaling. This study investigates the role of endothelial-derived S1P and ApoM-bound S1P in regulating vascular tone and blood pressure. Methods and Results ApoM knockout (ApoM KO) mice and mice lacking endothelial Spinster-2 (ECKO-Spns2) were infused with angiotensin II for 28 days. Blood pressure, measured by telemetry and tail-cuff, was significantly increased in both ECKO-Spns2 and ApoM KO versus control mice, at baseline and following angiotensin II. Notably, ECKO-Spns2 presented an impaired vasodilation to flow and blood pressure dipping, which is clinically associated with increased risk for cardiovascular events. In hypertension, both groups presented reduced flow-mediated vasodilation and some degree of impairment in endothelial NO production, which was more evident in ECKO-Spns2. Increased hypertension in ECKO-Spns2 and ApoM KO mice correlated with worsened cardiac hypertrophy versus controls. Conclusions Our study identifies an important role for Spinster-2 and ApoM-HDL in blood pressure homeostasis via S1P-NO signaling and dissects the pathophysiological impact of endothelial-derived S1P and ApoM of HDL-bound S1P in hypertension and cardiac hypertrophy.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Anion Transport Proteins - biosynthesis, genetics
- Apolipoproteins M - biosynthesis, genetics
- Disease Models, Animal - administration & dosage
- Endothelium, Vascular - metabolism, physiopathology
- Gene Expression Regulation - administration & dosage
- Hypertension - genetics, metabolism, physiopathology
- Lysophospholipids - biosynthesis, genetics
- Male - administration & dosage
- Mice - administration & dosage
- Mice, Knockout - administration & dosage
- RNA - genetics
- Sphingosine - analogs & derivatives, biosynthesis, genetics
- Vascular Stiffness - physiology
- Find related publications in this database (Keywords)
- apolipoprotein
- high blood pressure
- hypertension
- vascular tone regulation