Pharmacology and Technologies for Cardiovascular Diseases (PROTECT)
PROTECT team researches and develops pharmacological strategies and technologies to reduce the consequences of cardiovascular events such as myocardial infarction, heart failure or cardiac arrest. This research is based on an integrated approach that evolves from cellular models to clinical evaluations and in-depth preclinical studies. This translational approach has led to several clinical trials and the transfer of innovations to the industrial sector.
Objectives of the team
1- research therapeutic approaches to limit the consequences of a cardiac arrest. In particular, we are studying an innovative hypothermia strategy using total liquid ventilation of the lungs during shock following resuscitation;
2- Studying molecules likely to reduce vascular permeability during myocardial infarction or heart failure. In particular, we are evaluating the modulation of myocardial oedema and coronary microcirculation by angiopoietin-like derivatives 4 ;
3- study the heme oxygenase and carbon monoxide pathway in myocardial ischemia, with a focus on inflammatory mechanisms and cellular bioenergetics.
4- to search for new anti-ischemic molecules by targeting the mitochondrial toxicity of cholesterol. The role of the ligands of its translocation protein (TSPO) is particularly evaluated.
The team’s areas of research relate to areas of high societal impact since ischemic cardiovascular disease is one of the leading causes of mortality in humans worldwide. This also corresponds to an important issue for the health of pets.
The team includes scientists, pharmacists, veterinarians and physicians, providing a wide range of expertise. This allows us to consider research from the “fundamental” to the transfer to the human or veterinary clinic.
Moreover, the development of original pharmacological strategies or medical devices is fully in line with a valorisation approach. It is therefore research that has a strong potential for transfer and economic impact.
The team is organized into three groups led by Bijan Ghaleh, Roberto Motterlini and Renaud Tissier.
The laboratories are located at the Faculty of Medicine of Créteil and at the National Veterinary School of Alfort.
Panel M et al., Small-molecule inhibitors of cyclophilins block opening of the mitochondrial permeability transition pore and protect mice from hepatic ischemia/reperfusion injury.Gastroenterology, 2019 ; 157 : 1368-1382.
Portal et al., The CO-releasing molecule CORM-3 protects adult cardiomyocytes against hypoxia-reoxygenation by modulating pH restoration.Eur J Pharmacol. 2019 ; 862 : 172636.
Kohlhauer M et al., Protection against cardiac ischemia-reperfusion injury by hypothermia and by inhibition of succinate accumulation and oxidation is additive.
Basic Res Cardiol. 2019 ; 114 : 24.
Tissier R et al, Early blood transcriptomic signature predicts patients’ outcome after out-of-hospital cardiac arrest.Resuscitation. 2019 ; 138 :222-232.
Braud L et al, Carbon monoxide-induced metabolic switch in adipocytes improves insulin resistance in obese mice.JCI Insight. 2018 ; 3 : pii 123485.
Jozwiak M et al. Ivabradine improves left ventricular twist and untwist during chronic hypertension.Int J Cardiol. 2017 ; 252 : 175-180.
Musman J et al. A Tspo ligand prevents mitochondrial sterol accumulation and dysfunction during myocardial ischemia-reperfusion in hypercholesterolemic rats.Biochem Pharmacol. 2017 ; 142 : 87-95.
Chetboul V et al. Short-term efficacy and safety of torasemide and furosemide in 366 dogs with degenerative mitral valve disease: The TesT study.J Vet Intern Med. 2017 ; 31 : 1629-1642.