Abstract
Atherosclerosis with associated cardiovascular diseases remains one of the main causes of disability and death worldwide, requiring development of new solutions for prevention and treatment. Macrophages are the key effectors of a series of events involved in atherogenesis, such as inflammation, plaque formation, and changes in lipid metabolism. Some of these events were shown to be associated with mitochondrial dysfunction and excessive mitochondrial DNA (mtDNA) damage. Moreover, macrophages represent a promising target for novel therapeutic approaches that are based on the expression of various receptors and nanoparticle uptake. Lipid‐based gene delivery to mitochondria is considered to be an interesting strategy for mtDNA damage correction. To date, several nanocarriers and their modifications have been developed that demonstrate high transfection efficiency and low cytotoxicity. This review discusses the possibilities of lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy.
Highlights
Atherosclerosis is a multifactorial disease, which is characterized by the formation of fatty plaques in the arterial wall and chronic inflammatory response
The aim of this review is to summarize current knowledge on the use of lipid-based nanocarriers for targeted gene delivery to macrophage mitochondria and assess its role in future atherosclerosis therapy
Macrophage mitochondria, in particular, appear to be interesting from the point of view of future therapies development, as mitochondrial DNA (mtDNA) damage is associated with the pathology development
Summary
Atherosclerosis is a multifactorial disease, which is characterized by the formation of fatty plaques in the arterial wall and chronic inflammatory response. Atherosclerosis leads to narrowing of the lumen of the affected vessel and increases the risk of thrombosis, which can be followed by lethal events, such as ischemic stroke and sudden cardiac death.[1,2]. It is well-known that atherosclerosis development can be a result of acquired and inherited factors. Among the risk factors of atherosclerosis are dyslipidemia, arterial hypertension, diabetes mellitus, and old age.[3]. Monocytes and macrophages play leading roles at all stages of atherosclerosis development, contributing to the local inflammatory response, cholesterol accumulation, and plaque growth.[4]
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