Potential intervention target of atherosclerosis: Ferroptosis (Review)

Abstract

Atherosclerosis (AS) is a chronic inflammatory disease of the blood vessels, which is mainly characterized by the form of atherosclerotic plaques and vascular endothelial injury. Its formation involves abnormal lipid metabolism, oxidative stress and inflammation, as well as other processes. AS is the direct cause of various acute cardiovascular and cerebrovascular diseases, such as acute myocardial infarction and acute ischemic stroke. Early intervention in the atherosclerotic inflammatory process and lesion progression is beneficial, and has been associated with the primary prevention of a range of related diseases. Ferroptosis is a non-apoptotic form of cell death different from cell necrosis and autophagy, which has been shown to participate in atherogenesis and atherosclerotic progression through numerous signaling pathways. The main characteristic of ferroptosis is the formation of high levels of cellular iron catalytic free radicals, unsaturated fatty acid accumulation and iron-induced lipid reactive oxygen species accumulation, which can cause oxidative stress, and subsequent DNA, protein and lipid damage. There are numerous hypotheses about the pathogenesis of AS. At present, it has been suggested that ferroptosis can accelerate the progression of AS and that inflammation is associated with the whole process of AS. The mechanisms and signaling pathways related to the involvement of neuroinflammation and ferroptosis in the progression of AS, and therapeutic targets associated with ferroptosis have not yet been elucidated. The present review article evaluated the involvement of ferroptosis in the progression of AS from the perspectives of ferroptotic cell death, the pathogenesis of AS and nervous system inflammation, with the aim of exploring new therapeutic targets for AS. Contents1. Introduction 2. Iron and ferroptosis 3. Ferroptosis is involved in the formation and progression of AS 4. Ferroptosis accelerates the progression of AS, leading to ischemic stroke 5. Conclusion and future perspectives

Transcriptomics Analysis Revealed Key Genes Associated with Macrophage Autophagolysosome in Male ApoE−/− Mice Aortic Atherosclerosis

“…They may contribute to inflammation and endothelial dysfunction by participating in many signaling pathways. 34 Ferroptosis is a non-apoptotic form of cell death, different from cell necrosis and autophagy. It is characterized by high levels of iron-catalyzed free radicals and the accumulation of lipid reactive oxygen species induced by iron, resulting in oxidative stress and subsequent DNA, protein, and lipid damage.…”

Vascular Progenitor Cells: From Cancer to Tissue Repair

“…The organization of the vascular wall is well structured and consists of three different main functional layers: the intima, a single layer of endothelial cells, which provides an interface between blood and smooth muscle and contains vascular stem cells which are CD34 and c-kit-positive; the media, including smooth muscle cells, collagen and elastin; and the adventitia composed of undifferentiated dendritic cells, connective tissue, vasa vasorum and other cells including fibroblasts, pericytes, and cells CD34, Sca-1, c-kit, NG2 and GII1-positive. This well-organized vascular structure can deal with injuries that are often caused by several acute and chronic diseases including hypertension [ 2 ], atherosclerosis [ 3 ], diabetes [ 4 , 5 ], trauma [ 6 ], occlusions [ 7 ], hypoxia [ 8 ], primary cancerous lesions, and metastases [ 9 ] as well as catheter interventions [ 10 , 11 ].…”

Visualization of the Ferroptosis in Atherosclerotic Plaques with Nanoprobe Engineered by Macrophage Cell Membranes

“…35,36 Hence, inhibition of the ferroptosis of macrophages may become the potential target in AS. 37 X-ray computed tomography (CT), positron emission tomography (PET), ultrasonography (US), and magnetic resonance imaging (MRI) are applied for the identification of AS plaques in the clinic. 38−40 However, neither of these imaging techniques allows early-stage AS detection with the restriction of long scanning and postprocessing times.…”

“…Inhibition of ferroptosis may provide a new promising therapeutic approach for the treatment of AS. The death of macrophage foam cells including ferroptosis is a major contributor to the formation of lipid-rich necrotic core and a marked feature of plaque destabilization. , Hence, inhibition of the ferroptosis of macrophages may become the potential target in AS …”