Gene Expression of Protein Tyrosine Phosphatase 1B and Endoplasmic Reticulum Stress During Septic Shock
Protein Tyrosine Phosphatase 1B (PTP1B) and endoplasmic reticulum stress (ERS) are involved in the septic inflammatory response. Their inhibition is associated with improved survival in murine models of sepsis. In a recent publication in Frontiers in Medicine Dr Clavier et al showed in a study of 40 patients with septic shock that gene expression variation in blood samples of PTPN1 and ATF6 partly correlate with the evolution of septic organ failure and with markers of endothelial dysfunction. The recent identification of PTP1B as a novel negative regulator of host defense against sepsis may have potential therapeutic implications. However, further studies are needed to better understand PTP1B and ERS implication during sepsis in humans.
This autumn four PhD students have defended their thesis in our laboratory:
- Mouad Hamzaoui
- Bérénice Colleville
- Frédéric Roca
- Matthieu Leuillier
Dr Mouad Hamzaoui (Dir. Dominique Guerrot)
"Rôle de la dysfonction endothéliale dans les complications cardiovasculaires et rénales de la polykystose rénale autosomique dominante: intérêt d’une modulation pharmacologique par agonistes dopaminergiques"
Dr Bérénice Colleville (Dir. Eric Durand)
"Identification de nouvelles cibles thérapeutiques dans le rétrécissement aortique"
Dr Frédéric Roca (Dir Robinson Joannides)
"Évaluation in vivo de la viscosité pariétale des artères de conductance : impact du vieillissement, de la dysfonction endothéliale et de la réduction pharmacologique de la fréquence cardiaque"
Dr Matthieu Leuillier (Dir. Jeremy Bellien)
"Rôle de l'activité phosphatase de l'époxyde hydrolase soluble dans la régulation de l'homéostasie métabolique et cardiovasculaire"
Arterial wall viscosity is regulated by endothelium-derived NO and epoxyeicosatrienoic acids (EETs) under baseline physiological conditions. Whether these factors regulate arterial viscosity during blood flow increase and whether this mechanism is affected in patients with essential hypertensive have remained unknown.
In a recent publication in Atherosclerosis Dr Roca et al showed in a study of 18 untreated hypertensive patients and 14 normotensive controls that baseline arterial viscosity was increased in hypertensive patients. Whereas pharmacological inhibition of NO and/or EETs increased arterial viscosity in response to flow-mediated dilatation, these inhibitors did not modify the arterial viscosity in hypertensive patients.
Thus, the release of NO and EETs maintains a stable arterial wall viscosity during flow increase and this endothelial adaptive regulation is lost during essential hypertension, which may promote excessive viscous energy dissipation and cardiovascular uncoupling. Restoration of EETs availability with inhibitors of soluble epoxide hydrolase could thus constitute a promising pharmacological approach to restore the endothelial adaptive regulation of AWV.
Our publication demonstrating the benefits of PTP1B gene deletion on the cardiovascular consequences of aging published in Am J Physiol PMID: 29569957