Biology of cardiometabolic diseases
New interfaces in the biology of cardiometabolic diseases
Cardiovascular diseases linked to diabetes, atherosclerosis, obesity or liver diseases such as NASH are on the rise in France as in all developed countries; they are now grouped under the concept of cardiometabolic diseases. There are scientific bases for this concept consisting of the many interfaces between metabolism and organs: microbiota, adipose tissue, immune system. Yes Good that today‘hiu cardiovascular disease and metabolic can no longer be consideredare like the disease of an organ but require approaches multi–organs, systemics, taking Also taking into account the environment, nutrition and the activity physical.
Cholesterol
Historically, cholesterol metabolism is the first interface described between metabolism and cardiovascular diseases, particularly those linked to atherosclerosis responsible for the formation of atherosclerotic plaque in the lumen of vessels. For many years, the IHU teams have been studying the transport of cholesterol from its digestive absorption, its metabolism in the liver and up to its exchanges with the body’s cells. Their work has helped to establish the athero-protective role of HDL particles, known as “the good cholesterol”. The precise knowledge of cholesterol transport and metabolism has made it possible to identify new biomarkers, for example, to predict the evolution after a myocardial infarction and new therapeutic targets.
Adipose tissue
Fat tissue is one of the main interfaces between the metabolism and the organs in general, the heart and the vessels in particular. We distinguish the cutaneous fatty tissue from the visceral tissue around the organs, in particular the heart and the vessels. The latter has many biological functions, in the first place it is a source of fatty acids necessary for the metabolism, for example of the heart muscle. Visceral fatty tissue secretes numerous peptides which act locally or remotely like hormones, on the inflammatory state or the oxidative stress of the tissues.
The IHU ICAN teams were pioneers in describing the role played by fatty tissue around the heart in the risk of occurrence of the most common cardiac arrhythmia, atrial fibrillation. They showed that this fatty tissue could in certain circumstances promote fibrosis of the atrial myocardium, a mechanism of arrhythmias.
They identified the origin of this cardiac fatty tissue, which comes from the differentiation of resident progenitor cells in the outer layer of the heart, the epicardium. The recruitment of progenitor cells and their differentiation into fat cells occur during various cardiac stresses: work overload or metabolic stress These discoveries have opened up new perspectives for research on cardiac arrhythmias and in particular on the impact of metabolic diseases, obesity, syndrome metabolic, diabetes, on the accumulation of cardiac fatty tissue and its biological activity (Chua W et al. BMC Cardiovasc Disord. 2019).
The microbiota
The teams specializing in nutrition at the IHU have contributed to the identification of the relationships between cardiovascular diseases and the intestinal microbiota and in particular how intestinal dysbiosis promotes metabolic diseases. Microbial genetic richness is lowered during obesity and metabolic diseases conversely, high microbial richness is associated with healthy eating habits (Dao Front Physiol 2019). The Métacardis cohort set up within the framework of a European FP7 project and co-financed by the IHU ICAN, has made it possible to show that treatment with a statin improves the reduction in microbial genetic diversity in patients with cardiometabolic diseases (Vieira-Silva S et al Nature 2020). Imidazole propionate from bacterial metabolism from certain nutrients is increased in type 2 diabetic patients and associated with the presence of microbial dysbiosis (Molinaro et al Nature communication 2020).
Liver
The liver is at the center of the metabolic syndrome and is involved in the metabolism of carbohydrates and lipids. NASH (metabolic steatopathy) is one of the hepatic manifestations of insulin resistance, with consequences not only at the level of the liver (progression of fibrosis, cirrhosis and its complications) but also at the level of cardiometabolic risk factors (cardiovascular diseases, diabetes, etc.).
As a result, the liver is at the heart of ICAN’s topics of interest in a cross-cutting approach that links the various pathologies linked to the metabolic syndrome and cardiovascular diseases. ICAN is the promoter of an innovative, complex and multidisciplinary care circuit dedicated to patients with NASH ( the NASH Clinic ) thus allowing precision phenotyping and a personalized therapeutic approach adapted to each patient.
ICAN actively supports the development of new molecules to treat NASH. ICAN participates in several European consortia around NASH – LITMUS and EU-PEARL (IMI2 and EFPIA funding). The hepatology team within the IHU ICAN has carried out important work focused on the natural history of NASH (Pais J Hepatol 2013), the relationship with cardiovascular diseases (Pais J Hepatol 2016, Pais Hepatology 2019 and the CORO-NASH project) and more recently, in collaboration with the AP-HP, the relationship between the liver and COVID-19 (STRAT-COVID project). Finally, the IHU is involved in fundamental work aimed at exploring the pathophysiological mechanisms involved in NASH and the progression of fibrosis (ceramides, sphingolipids, apoptosis pathways and cell death) (work C Housset, F Foufelle, J Gautheron, HumanHepCell).