NCT03980548

Targeting Mitochondrial Fusion and Fission to Prevent Atherosclerosis: Getting the Balance Right

Targeting Mitochondrial Fusion and Fission to Prevent Atherosclerosis: Getting the Balance Right - MITOFFA

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 200 (estimated)
• Sponsor: National Heart Centre Singapore · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Accepted

Summary

Our preliminary data suggests that pharmacological inhibition of the mitochondrial fission protein, Drp1, reduced atherosclerotic plaque volume and attenuated macrophage accumulation within the plaque in an ApoE-/- mouse model of wire-induced carotid arterial injury. Furthermore, we hypothesize that modulation of mitochondrial morphology and metabolism with Drp1 inhibition prevents atherosclerosis by reducing monocyte activation and migration. In this research proposal, our overall objective will be to investigate the role of Drp1 in human monocytes and macrophages as novel therapeutic targets for preventing atherosclerosis.

Detailed description

Study 1 (tissue sample study): To investigate the changes in mitochondrial function and pro-inflammatory markers in human arterial atherosclerotic plaques. Hypothesis: Macrophages from femoral artery atherosclerotic plaques in patients with peripheral artery disease will display upregulation of mitochondrial fission proteins and features of pro-inflammatory activation. Study 2 (white blood cell study): To investigate the changes in mitochondrial function and pro-inflammatory markers in white blood cells from patients with stable and unstable coronary artery didease (CAD). Hypothesis: Monocytes from patients with unstable CAD will display upregulation of Drp1 and features of pro-inflammatory activation, mitochondrial fission, impaired mitochondrial respiratory function, and perturbed metabolism, when compared to monocytes from patients with stable CAD.

Conditions

• CAD Patients

Interventions

Type	Name	Description
PROCEDURE	CABG	Patients undergoing coronary artery bypass graft and patient presented with ACS undergoing PCI

Timeline

• Start date: 2018-10-10
• Primary completion: 2020-03-31
• Completion: 2020-03-31
• First posted: 2019-06-10
• Last updated: 2019-06-10

Locations

1 site across 1 country: Singapore