The Role of Pioglitazone in Vascular Transcriptional Remodeling
NCT05775380 · Status: RECRUITING · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 20
Last updated 2024-01-12
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, the role of pioglitazone hydrochloride 45mg/day for five days in volunteers undergoing coronary artery bypass grafting (BVR) will be investigated in order to verify the vascular expression of SPhk1, transcriptome and vascular proteome remodeling, as well as S1P content in HDL.
Conditions
- Myocardial Reperfusion Injury
Interventions
- DRUG
-
Pioglitazone 45 mg
We investigated the role of pioglitazone hydrochloride 45mg/day for five days in patients admitted for coronary artery bypass grafting (CABG) in order to investigate vascular SPhk1 expression, vascular transcriptome and proteome remodeling, as well as S1P content in HDL
Sponsors & Collaborators
-
University of Campinas, Brazil
lead OTHER
Principal Investigators
-
Andrei Sposito, Professor · University of Campinas, Brazil
Study Design
- Allocation
- RANDOMIZED
- Purpose
- PREVENTION
- Masking
- QUADRUPLE
- Model
- PARALLEL
Eligibility
- Min Age
- 40 Years
- Max Age
- 70 Years
- Sex
- MALE
- Healthy Volunteers
- No
Timeline & Regulatory
- Start
- 2023-06-15
- Primary Completion
- 2024-06-28
- Completion
- 2024-12-22
Countries
- Brazil
Study Locations
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