Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

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.

Effects of Lipopolysaccharide-Binding Protein (LBP) Single Nucleotide Polymorphism (SNP) in Infections, Inflammatory Diseases, Metabolic Disorders and Cancers

“…As the leading cause of myocardial infarction and stroke (70), atherosclerosis (AS) is a complex disease and involves a series of pathophysiological processes such as inflammation and lipid metabolism (71). Hubacek et al demonstrated that the frequency of LBP 1306T>C (rs2232618) C allele (Leu436) homozygotes is about threefold in patients with myocardial infarction than in controls (60).…”

“…As the leading cause of myocardial infarction and stroke ( 70 ), atherosclerosis (AS) is a complex disease and involves a series of pathophysiological processes such as inflammation and lipid metabolism ( 71 ). Hubacek et al.…”

Targeting the Microenvironment of Vulnerable Atherosclerotic Plaques: An Emerging Diagnosis and Therapy Strategy for Atherosclerosis

“…With the development of genetics and molecular biology, growing evidence suggests that the pathogenesis of AS involves lipid metabolism, inflammation, oxidative stress, and innate and adaptive immune responses, which provide new perspectives for the treatment of atherosclerotic plaques. [118] Based on the microenvironment of vulnerable atherosclerotic plaques, the emergence of nanomedicine has brought numerous novel therapeutic strategies, achieving precise therapy for atherosclerotic plaques and boosting the efficacy of current plaque treatments (see Table 2)…”

Atherosclerosis as Mitochondriopathy: Repositioning the Disease to Help Finding New Therapies

“…It is therefore possible that mtDNA damage is the primary event that induces excessive ROS generation, violation of the mitochondrial membrane potential and mitochondrial dysfunction followed by the release of cytochrome C and activation of apoptotic pathways. In addition, damaged mtDNA can be recognized by the body as an endogenous damage-associated molecular pattern (DAMP), which provokes the inflammatory response ( 26 ).…”

“…Penetration through the outer and inner membranes of the mitochondria by these particles is ensured by the presence of hydrophobic and positively charged ligands that facilitate the process of endosomal transport. Lipid carriers are currently regarded as low toxic and highly selective transport systems ( 26 ).…”