The Role of Pioglitazone in Vascular Transcriptional Remodeling

• Status: Not yet recruiting
• Trial end date: 2023-12-20
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Campinas, Brazil
• Treatments: Pioglitazone

Criteria

Inclusion Criteria:

• Male individuals

• Individuals undergoing CABG surgery for coronary artery disease

• Be over 40 years of age

• BMI between 20 and 34.9kg/m2

Exclusion Criteria:

• Diabetes, BMI greater than 35 kg/m2, steatohepatitis, chronic kidney disease, systemic vasculitis, conditions that induce systemic inflammation such as psoriasis and systemic lupus erythematosus

• contraindications to the use of pioglitazone hydrochloride (heart failure, liver failure - AST or ALT > 2.5x upper normal limit, history of bladder cancer or macroscopic hematuria without investigation)

• moderate or severe valve disease

• need for concomitant use of other hypoglycemic therapies during hospitalization, particularly insulin

• peripheral edema

• recent hospitalization

• known allergy to any study drug

• polyuria, polydipsia, weight loss, or other clinical signs of volume depletion or diabetes, difficult-to-control systemic arterial hypertension, defined as individuals taking 4 or more drugs

• those who withdraw the Informed Consent Form (TCLE), or who, for some reason, are not able to sign or understand the TCLE

• history of gastrointestinal disorders that may interfere with study drug absorption

• research participant who is participating in other clinical trials or whose participation ended less than six months ago

• Research participant who has left ventricular dysfunction