Branched-chain amino acid catabolic defect in vascular smooth muscle cells drives thoracic aortic dissection via mTOR hyperactivation

Free Radical Biology and Medicine, Год журнала: 2023, Номер 210, С. 25 - 41

Опубликована: Ноя. 11, 2023

Язык: Английский

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Higher matrix stiffness promotes VSMC senescence by affecting mitochondria–ER contact sites and mitochondria/ER dysfunction

The FASEB Journal, Год журнала: 2023, Номер 37(12)

Опубликована: Ноя. 23, 2023

Abstract Abdominal aortic aneurysm (AAA) is a prevalent condition characterized by the weakening and bulging of abdominal aorta. This study aimed to investigate impact stiff matrix on vascular smooth muscle cells (VSMCs) in AAA development. Bioinformatics analysis revealed that differentially expressed genes (DEGs) VSMCs an mouse model were enriched cellular senescence related pathways. To simulate aging‐related changes, cultured matrices, compared those soft matrices exhibited senescence. Furthermore, mutual distance between mitochondria endoplasmic reticulum (ER) was increased, indicating altered mitochondria–endoplasmic contacts (MERCs). The observed upregulation reactive oxygen species (ROS) levels, antioxidant gene expression, decreased mitochondrial membrane potential suggested presence dysfunction matrix. Additionally, induction ER stress‐related indicated dysfunction. These findings collectively impaired functionality both Moreover, our data high lipid levels exacerbated effects stiffness senescence, MERC sites, mitochondria/ER Importantly, treatment with antilipemic agent CI‐981 effectively reversed these detrimental effects. provide insights into role stiffness, dysfunction, stress, metabolism development, suggesting therapeutic targets for intervention.

Язык: Английский

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Cannabidiol protects against acute aortic dissection by inhibiting macrophage infiltration and PMAIP1-induced vascular smooth muscle cell apoptosis

Journal of Molecular and Cellular Cardiology, Год журнала: 2024, Номер 189, С. 38 - 51

Опубликована: Фев. 20, 2024

Acute aortic dissection (AAD) progresses rapidly and is associated with high mortality; therefore, there remains an urgent need for pharmacological agents that can protect against AAD. Herein, we examined the therapeutic effects of cannabidiol (CBD) in AAD by establishing a suitable mouse model. In addition, performed human single-cell RNA sequencing bulk to elucidate potential underlying mechanism CBD. Pathological assays vitro studies were verify results bioinformatic analysis explore function β-aminopropionitrile (BAPN)-induced model, CBD reduced AAD-associated morbidity mortality, alleviated abnormal enlargement ascending aorta arch, suppressed macrophage infiltration vascular smooth muscle cell (VSMC) apoptosis. Bioinformatic revealed pro-apoptotic gene PMAIP1 was highly expressed samples, could inhibit Pmaip1 expression mice. Using VSMCs (HAVSMCs) co-cultured M1 macrophages, HAVSMCs mitochondrial-dependent apoptosis suppressing BAPN-induced overexpression macrophages. potentially mediates regulating Bax Bcl2 expression. Accordingly, mortality mitigated progression The CBD-induced mediated (primarily macrophages)-induced VSMC Our findings offer novel insights into macrophages interaction during progression, highlighting as candidate treatment.

Язык: Английский

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miRNA Regulation of Cell Phenotype and Parietal Remodeling in Atherosclerotic and Non-Atherosclerotic Aortic Aneurysms: Differences and Similarities

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2641 - 2641

Опубликована: Фев. 24, 2024

Aortic aneurysms are a serious health concern as their rupture leads to high morbidity and mortality. Abdominal aortic (AAAs) thoracic (TAAs) exhibit differences similarities in pathophysiological pathogenetic features. AAA is multifactorial disease, mainly associated with atherosclerosis, characterized by relevant inflammatory response calcification. TAA rarely atherosclerosis some cases genetic mutations such Marfan syndrome (MFS) bicuspid valve (BAV). MFS-related non-genetic or sporadic share degeneration endothelial-to-mesenchymal transition (End-Mt) fibrosis, whereas BAV TAA, calcification prevails. microRNA (miRNAs) contribute the regulation of aneurysmatic remodeling. miRNAs class non-coding RNAs, which post-transcriptionally regulate gene expression. In this review, we report involvement deregulated different remodeling characterizing AAAs TAAs. AAA, miRNA deregulation appears be involved parietal response, smooth muscle cell (SMC) apoptosis wall promotes End-Mt, SMC myofibroblastic phenotypic switching fibrosis glycosaminoglycan accumulation. sustains Those may support development more personalized therapeutic approaches.

Язык: Английский

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Innovation in pathogenesis and management of aortic aneurysm

World Journal of Experimental Medicine, Год журнала: 2024, Номер 14(2)

Опубликована: Июнь 13, 2024

Aortic aneurysm (AA) refers to the persistent dilatation of aorta, exceeding three centimeters. Investigating pathophysiology this condition is important for its prevention and management, given responsibility more than 25000 deaths in United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, immune system atherosclerosis have been implicated development. Inflammatory markers such as transforming growth factor β, interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-2 many may contribute phenomenon. Several genetic disorders Marfan syndrome, Ehler-Danlos syndrome Loeys-Dietz also associated with disease. Recent years has seen investigation novel management AA, exploring implication different suppressors, role radiation shrinkage prevention, well minimally invasive newly hypothesized surgical methods. In narrative review, we aim present new contributing factors involved AA. We highlighted methods that demonstrated promising benefits clinical outcomes

Язык: Английский

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