The Role of Pioglitazone in Vascular Transcriptional Remodeling
Status:
Not yet recruiting
Trial end date:
2023-12-20
Target enrollment:
Participant gender:
Summary
Acute myocardial infarction (AMI) remains the leading cause of death worldwide. In this
scenario, early coronary reperfusion is the main therapeutic strategy as it substantially
reduces mortality. Paradoxically, however, reperfusion triggers additional tissue damage that
accounts for about 50% of the infarcted heart mass, i.e., ischemia and reperfusion injury
(IRL). In this context, sphingosine-1-phosphate (S1P) is a sphingolipid synthesized by
sphingosine kinases (Sphk), carried in plasma bound to high-density lipoprotein (HDL) and
released after cellular damage such as LIR. Particularly, in animal models of AMI, therapies
targeting downstream S1P receptor signaling triggered by HDL/S1P are able to promote
endothelial barrier functions and attenuate secondary damage to LIR. Thus, the molecular
control of sphingosine kinase 1 (Sphk1) transcription during LIR in vivo or during
hypoxia/reoxygenation (H/R) in vitro may represent an important mechanism for maintaining
endothelial homeostasis since it promotes the generation of S1P and this may promote
subsequent HDL enrichment. Thus, we will investigate the role of pioglitazone hydrochloride
45mg/day for five days or placebo in volunteers undergoing coronary artery bypass grafting
(BVR) in order to investigate the vascular expression of SPhk1, transcriptome and vascular
proteome remodeling, as well as S1P content in HDL.