Mitochondrial bioenergetics and therapeutic intervention in cardiovascular disease
1University of Glasgow, Institute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, 126 University Place, Glasgow G12 8TA, United Kingdom.
Insights
Cardiovascular disease, a leading cause of death, is linked to atherosclerotic plaque rupture. Mitochondrial dysfunction and ATP loss in vascular smooth muscle cells (VSMCs) may drive this vulnerability, suggesting new therapeutic targets.
Area of Science:
- Cardiovascular Medicine
- Cellular Biology
- Mitochondrial Biology
Background:
- Cardiovascular disease (CVD) is the leading cause of mortality globally, with atherosclerosis accounting for a significant portion of these deaths.
- Atherosclerotic plaque rupture, often due to vascular smooth muscle cell (VSMC) cap integrity loss, is a critical event leading to adverse outcomes.
- Mitochondrial DNA damage and dysfunction have emerged as potential contributors to VSMC vulnerability and plaque instability.
Purpose of the Study:
- To investigate the role of mitochondrial dysfunction in vascular smooth muscle cell (VSMC) viability and its contribution to atherosclerotic plaque rupture.
- To explore therapeutic strategies targeting mitochondrial dysfunction and ATP synthesis for mitigating plaque vulnerability.
Main Methods:
- Analysis of mitochondrial DNA damage and reactive species production in atherosclerotic plaques.
- Assessment of ATP levels and cellular energetic status in VSMCs under stress conditions.
- Evaluation of therapeutic interventions aimed at restoring mitochondrial function and energy production.
Main Results:
- Mitochondrial dysfunction and associated reactive species production contribute to DNA damage and cellular senescence in VSMCs within atherosclerotic plaques.
- Reduced ATP levels due to mitochondrial dysfunction impair VSMC function and compromise plaque stability.
- Strategies enhancing ATP synthesis through energetic reconfiguration show potential in delaying plaque rupture kinetics.
Conclusions:
- Mitochondrial dysfunction is a key factor in VSMC vulnerability and atherosclerotic plaque rupture.
- Targeting mitochondrial health and cellular energetics represents a promising therapeutic avenue for managing cardiovascular disease.
- Further research into energetic reconfiguration strategies could offer novel treatments for preventing plaque rupture.
Abstract:
Cardiovascular disease remains the commonest form of mortality and morbidity in the Western World. It accounts for more deaths than the combined incidence of all cancers. There remains an urgency to identify and translate therapies to reduce the effects of this disease and its associated co-morbidities. Atherosclerotic disease accounts for over two thirds of all cardiovascular related deaths. Arterial vessel wall plaques rupture and cause death due to loss of integrity of the overlaying vascular smooth muscle cell (VSMC) cap. Although plaques contain a heterogeneous pool of different cell types, it is the VSMCs that by their nature are responsible for rupture. VSMC are the primary source of extracellular matrix and collagen and it has been suggested that loss of viability and vitality of these cells contributes to plaque vulnerability and rupture. While DNA damage has long been associated with atherosclerotic plaques only relatively recently has the contribution of mitochondrial DNA damage been suggested to play a role. The mitochondrial respiratory chain is a source of ATP that the cell requires for all its energetic functions but is also a source of free radicals that produce reactive species (RS). While these RS exacerbate DNA damage and attack lipids and proteins, it is the loss of ATP that may ultimately be more detrimental. Therapeutic intervention for mitochondria dysfunction is one route on alleviating this burden. Finding alternative sources of ATP synthesis by energetic reconfiguration may also provide a vital link in delaying the kinetics of plaque rupture.
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
01:45Mitochondrial Membranes
01:37Mitochondria