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Sphingosine-1-Phosphate Attenuates Lipopolysaccharide-Induced Pericyte Loss via Activation of Rho-A and MRTF-A.
Abdel Rahman, Farah; d'Almeida, Sascha; Zhang, Tina; Asadi, Morad; Bozoglu, Tarik; Bongiovanni, Dario; von Scheidt, Moritz; Dietzel, Steffen; Schwedhelm, Edzard; Hinkel, Rabea; Laugwitz, Karl Ludwig; Kupatt, Christian; Ziegler, Tilman.
Afiliação
  • Abdel Rahman F; Klinik & Poliklinik für Innere Medizin I, Klinikum Rechts der Isar, TU Munich, Munich, Germany.
  • d'Almeida S; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
  • Zhang T; Klinik & Poliklinik für Innere Medizin I, Klinikum Rechts der Isar, TU Munich, Munich, Germany.
  • Asadi M; Klinik & Poliklinik für Innere Medizin I, Klinikum Rechts der Isar, TU Munich, Munich, Germany.
  • Bozoglu T; Klinik & Poliklinik für Innere Medizin I, Klinikum Rechts der Isar, TU Munich, Munich, Germany.
  • Bongiovanni D; Klinik & Poliklinik für Innere Medizin I, Klinikum Rechts der Isar, TU Munich, Munich, Germany.
  • von Scheidt M; Klinik & Poliklinik für Innere Medizin I, Klinikum Rechts der Isar, TU Munich, Munich, Germany.
  • Dietzel S; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
  • Schwedhelm E; DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
  • Hinkel R; Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
  • Laugwitz KL; Walter-Brendl-Center for Experimental Medicine, LMU Munich, Munich, Germany.
  • Kupatt C; Center for Experimental Medicine, Institute of Clinical Pharmacology and Toxicology, Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Ziegler T; Klinik & Poliklinik für Innere Medizin I, Klinikum Rechts der Isar, TU Munich, Munich, Germany.
Thromb Haemost ; 121(3): 341-350, 2021 Mar.
Article em En | MEDLINE | ID: mdl-33011963
ABSTRACT
The high mortality seen in sepsis is caused by a systemic hypotension in part owing to a drastic increase in vascular permeability accompanied by a loss of pericytes. As has been shown previously, pericyte retention in the perivascular niche during sepsis can enhance the integrity of the vasculature and promote survival via recruitment of adhesion proteins such as VE-cadherin and N-cadherin. Sphingosine-1-phosphate (S1P) represents a lipid mediator regulating the deposition of the crucial adhesion molecule VE-cadherin at sites of interendothelial adherens junctions and of N-cadherin at endothelial-pericyte adherens junctions. Furthermore, in septic patients, S1P plasma levels are decreased and correlate with mortality in an indirectly proportional way. In the present study, we investigated the potential of S1P to ameliorate a lipopolysaccharide-induced septic hypercirculation in mice. Here we establish S1P as an antagonist of pericyte loss, vascular hyperpermeability, and systemic hypotension, resulting in an increased survival in mice. During sepsis S1P preserved VE-cadherin and N-cadherin deposition, mediated by a reduction of Src and cadherin phosphorylation. At least in part, this effect is mediated by a reduction of globular actin and a subsequent increase in nuclear translocation of MRTF-A (myocardin-related transcription factor A). These findings indicate that S1P may counteract pericyte loss and microvessel disassembly during sepsis and additionally emphasize the importance of pericyte-endothelial interactions to stabilize the vasculature.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Esfingosina / Lisofosfolipídeos / Transativadores / Sepse / Pericitos / Proteína rhoA de Ligação ao GTP Limite: Animals Idioma: En Revista: Thromb Haemost Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Esfingosina / Lisofosfolipídeos / Transativadores / Sepse / Pericitos / Proteína rhoA de Ligação ao GTP Limite: Animals Idioma: En Revista: Thromb Haemost Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha