Fight Aging!

Atherosclerosis is the growth of fatty lesions in blood vessel walls, ultimately leading to a heart attack or stroke when an unstable lesion ruptures. Atherosclerosis is primarily a condition of macrophage dysfunction, in which these cells fail to keep up with their task of removing excess cholesterol from blood vessel walls in order to return it to to the bloodstream for transport back to the liver. The local excess of cholesterol is largely the proximate cause of this macrophage dysfunction, so as the amount of cholesterol grows, macrophages become ever less capable of dealing with it. They die, adding their mass to the lesion, while signaling for reinforcements that will suffer the same fate.

That said, this is a description of how atherosclerosis progresses once it gets started. How do the initial small excesses of cholesterol form in the first place? Most of the underlying root causes of aging are involved in the growing inability of macrophages to keep up with the task of cholesterol transport. Further, altered behavior of other cell populations with advancing age, in the liver and blood vessel walls, may be capable of disrupting cholesterol transport from the liver to the rest of the body, leading to excess deposits in blood vessels. In today's open access paper, researchers focus in on the age-related decline in mitochondrial function in the context of atherosclerosis: would improving mitochondrial function help?

Effects of mitochondrial dysfunction on cellular function: Role in atherosclerosis

Atherosclerosis is the basis of a large proportion of fatal cardiovascular events, and a significant number of cardiovascular-related deaths can be attributed to the rupture of atherosclerotic plaques. Thinning of the covered fibrous cap formed by vascular smooth muscle cells (VSMCs) results in cap rupture and erosion, which is responsible for the majority of cardiovascular-related deaths from myocardial infarction and stroke. Atherosclerosis is an age-associated disorder; however, with the development of non-invasive diagnostic methods and the accumulation of knowledge in postmortem research, asymptomatic lesions have been described in young adults, suggesting that atherosclerosis is a chronic disease that develops at a much younger age than previously thought.

Atherosclerosis is now widely accepted to begin with endothelial dysfunction and lipid deposits, which progress through macrophage infiltration. In atherosclerosis-prone areas, the chronic inflammatory response and impaired lipoprotein metabolism are among the major contributors to atherosclerotic lesion formation. The first idea linking mitochondria to atherosclerosis was reported in 1970, but it is only recently that increasing evidence has highlighted the key role of mitochondrial dysfunction in the pathogenesis of atherosclerosis. Mitochondrial dysfunction can induce high levels of oxidative stress and high rates of apoptosis, which can cause endothelial dysfunction and increase the vascular disease burden. The increase in reactive oxygen species (ROS) production in mitochondria, accumulation of mitochondrial DNA damage, and progressive respiratory chain dysfunction are all related to atherosclerosis.

Mitochondrial dysfunction is believed to result in an increase in reactive oxygen species, leading to oxidative stress, chronic inflammation, and intracellular lipid deposition, all of which can contribute to the pathogenesis of atherosclerosis. Critical cells, including endothelial cells, vascular smooth muscle cells, and macrophages, play an important role in atherosclerosis. Mitochondrial function is also involved in maintaining the normal function of these cells. To better understand the relationship between mitochondrial dysfunction and atherosclerosis, this review summarizes the findings of recent studies and discusses the role of mitochondrial dysfunction in the risk factors and critical cells of atherosclerosis.