Two Subpopulations of Human Monocytes That Differ by Mitochondrial Membrane Potential

Area of Science:

• Immunology
• Cell Biology
• Cardiovascular Disease

Background:

• Atherosclerosis involves chronic arterial wall inflammation.
• Altered proinflammatory activity of circulating monocytes is observed in atherosclerosis patients.
• Mitochondrial DNA (mtDNA) mutations in monocytes are linked to atherosclerosis progression.

Purpose of the Study:

• To investigate changes in mitochondrial function of circulating monocytes in atherosclerosis.
• To test the hypothesis that atherosclerosis is associated with altered monocyte mitochondrial function.

Main Methods:

• Live staining of mitochondria in CD14+ monocytes from healthy donors and atherosclerosis patients using MitoTracker Orange CMTMRos dye.
• Assessment of mitochondrial membrane potential and functional activity.
• Evaluation of the proportion of MitoTracker-low monocytes and their correlation with lipopolysaccharide (LPS)-induced proinflammatory activation and intima-media thickness.

Main Results:

• A subset of monocytes, termed MitoTracker-low monocytes, exhibited reduced mitochondrial functional activity.
• These MitoTracker-low monocytes showed partially preserved mitochondrial function.
• An increased proportion of MitoTracker-low monocytes was associated with the presence of atherosclerotic plaques.
• Higher numbers of MitoTracker-low monocytes correlated with reduced proinflammatory activation of cells.

Conclusions:

• Circulating monocytes with mitochondrial dysfunction are present in atherosclerosis.
• The proportion of these dysfunctional monocytes is associated with chronic inflammation and atherosclerosis development.
• Mitochondrial dysfunction in monocytes may play a role in modulating the inflammatory response in atherosclerosis.