Molecular Dysfunctions of Mitochondria‐Associated Endoplasmic Reticulum Contacts in Atherosclerosis

Wang, Xiaojiao; Luo, Di; Wu, Sisi

doi:10.1155/2021/2424509

Cited by 11 publications

(9 citation statements)

References 89 publications

(100 reference statements)

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“…In this proteomics study, we observed several inflammatory-related GO BPs (e.g., innate immune response, response to cytokines) that are upregulated in ECs during inflammation which are potentially impacted during atherosclerosis and may serve as targets of interest. Atherosclerosis also has a significant impact on metabolic-related processes [ 45 , 46 , 47 , 48 ], and we identified additional BPs that alter the reactive oxygen species, reactive nitrogen species and lipid production in ECs (e.g., the positive regulation of reactive oxygen species, metabolic process, nitric oxide biosynthetic process, response to lipid). Thus, the current study characterizes a number of underlying processes and associated proteins that occur during inflammation and encourages future proteomic studies of EC dysfunction during vascular disease progression, such as atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach

Rossi

Langston

Singh

et al. 2022

IJMS

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A key aspect of cytokine-induced changes as observed in sepsis is the dysregulated activation of endothelial cells (ECs), initiating a cascade of inflammatory signaling leading to leukocyte adhesion/migration and organ damage. The therapeutic targeting of ECs has been hampered by concerns regarding organ-specific EC heterogeneity and their response to inflammation. Using in vitro and in silico analysis, we present a comprehensive analysis of the proteomic changes in mouse lung, liver and kidney ECs following exposure to a clinically relevant cocktail of proinflammatory cytokines. Mouse lung, liver and kidney ECs were incubated with TNF-α/IL-1β/IFN-γ for 4 or 24 h to model the cytokine-induced changes. Quantitative label-free global proteomics and bioinformatic analysis performed on the ECs provide a molecular framework for the EC response to inflammatory stimuli over time and organ-specific differences. Gene Ontology and PANTHER analysis suggest why some organs are more susceptible to inflammation early on, and show that, as inflammation progresses, some protein expression patterns become more uniform while additional organ-specific proteins are expressed. These findings provide an in-depth understanding of the molecular changes involved in the EC response to inflammation and can support the development of drugs targeting ECs within different organs. Data are available via ProteomeXchange (identifier PXD031804).

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Section: Discussionmentioning

confidence: 99%

Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach

Rossi

Langston

Singh

et al. 2022

IJMS

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“…One candidate could be protein pair VAP-PTPI51, which modulates the tightness of membrane connection and mediates substance flow, including lipids and ions at the ER-MT MCSs (or MAM). Loss of VAP-PTPI51 loosens the connection and induces basal autophagy in a Ca 2+ -dependent manner, whereas its overexpression tightens the connection and impairs this autophagy process (Wang et al, 2021). It is worth exploring whether VAPB-PTPI51 directly influences atherosclerosis by alternating macrophage autophagy or cholesterol transportation.…”

Section: Role Of Mcss In Atherosclerosis Developmentmentioning

confidence: 99%

Membrane contact sites orchestrate cholesterol homeostasis that is central to vascular aging

Pang

Jin

et al. 2023

WIREs Mechanisms of Disease

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Chronological age causes structural and functional vascular deterioration and is a well‐established risk factor for the development of cardiovascular diseases, leading to more than 40% of all deaths in the elderly. The etiology of vascular aging is complex; a significant impact arises from impaired cholesterol homeostasis. Cholesterol level is balanced through synthesis, uptake, transport, and esterification, the processes executed by multiple organelles. Moreover, organelles responsible for cholesterol homeostasis are spatially and functionally coordinated instead of isolated by forming the membrane contact sites. Membrane contact, mediated by specific protein–protein interaction, pulls opposing organelles together and creates the hybrid place for cholesterol transfer and further signaling. The membrane contact‐dependent cholesterol transfer, together with the vesicular transport, maintains cholesterol homeostasis and has intimate implications in a growing list of diseases, including vascular aging‐related diseases. Here, we summarized the latest advances regarding cholesterol homeostasis by highlighting the membrane contact‐based regulatory mechanism. We also describe the downstream signaling under cholesterol homeostasis perturbations, prominently in cholesterol‐rich conditions, stimulating age‐dependent organelle dysfunction and vascular aging. Finally, we discuss potential cholesterol‐targeting strategies for therapists regarding vascular aging‐related diseases.This article is categorized under: Cardiovascular Diseases > Molecular and Cellular Physiology

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“…Vascular smooth muscle cells (VSMCs) are also involved in this process. Being activated by PDGF (platelet-derived growth factor) appeared to be associated with reduced Mfn2, while fission inhibition decreased VSMC proliferation [ 64 ]. The suppression of Drp1 was shown to significantly decrease VSMC proliferation and migration, as well as the formation of neointima.…”

Section: Mitochondrial Dynamics In Atherosclerosis and Strokementioning

confidence: 99%

Mitochondrial Implications in Cardiovascular Aging and Diseases: The Specific Role of Mitochondrial Dynamics and Shifts

Poznyak

Кириченко

Borisov

et al. 2022

IJMS

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Cardiovascular disease has been, and remains, one of the leading causes of death in the modern world. The elderly are a particularly vulnerable group. The aging of the body is inevitably accompanied by the aging of all its systems, and the cardiovascular system is no exception. The aging of the cardiovascular system is a significant risk factor for the development of various diseases and pathologies, from atherosclerosis to ischemic stroke. Mitochondria, being the main supplier of energy necessary for the normal functioning of cells, play an important role in the proper functioning of the cardiovascular system. The functioning of each individual cell and the organism as a whole depends on their number, structure, and performance, as well as the correct operation of the system in removing non-functional mitochondria. In this review, we examine the role of mitochondria in the aging of the cardiovascular system, as well as in diseases (for example, atherosclerosis and ischemic stroke). We pay special attention to changes in mitochondrial dynamics since the shift in the balance between fission and fusion is one of the main factors associated with various cardiovascular pathologies.

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Molecular Dysfunctions of Mitochondria‐Associated Endoplasmic Reticulum Contacts in Atherosclerosis

Cited by 11 publications

References 89 publications

Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach

Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach

Membrane contact sites orchestrate cholesterol homeostasis that is central to vascular aging

Mitochondrial Implications in Cardiovascular Aging and Diseases: The Specific Role of Mitochondrial Dynamics and Shifts

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