PAC1 Agonist Maxadilan Reduces Atherosclerotic Lesions in Hypercholesterolemic ApoE-Deficient Mice

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13245 - 13245

Опубликована: Дек. 10, 2024

A possible involvement of immune- and vasoregulatory PACAP signaling at the PAC1 receptor in atherogenesis plaque-associated vascular inflammation has been suggested. Therefore, we tested agonist Maxadilan selective antagonist M65 on plaque development lumen stenosis ApoE−/− atherosclerosis model for effects atherogenesis. Adult male mice were fed a cholesterol-enriched diet (CED) or standard chow (SC) treated with Maxadilan, Sham. Effects treatment atherosclerotic plaques, stenosis, apoptosis pro-inflammatory signatures analyzed brachiocephalic trunk (BT). The percentage exhibiting plaques under SC CED was lower than that Sham indicating opposite M65. application inhibited compared to mice. In spite increased cholesterol levels, Maxadilan-treated similar SC. contrast, did not reveal significant influence stenosis. significantly reduced TNF-α-immunoreactive (TNF-α+) area CED, but IL-1β+ after remained unchanged caspase-3 immunoreactive (caspase-3+) tunica media both, without affecting lipid content plaques. Despite persistent hypercholesterolemia, reduces TNF-α driven inflammation. Our data suggest provides atheroprotection by acting downstream hypercholesterolemia-induced This implicates potential PAC1-specific drugs against even beyond statins PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors.

Язык: Английский

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Colchicine reduces neointima formation and VSMC phenotype transition by modulating SRF-MYOCD activation and autophagy

Acta Pharmacologica Sinica, Год журнала: 2024, Номер unknown

Опубликована: Дек. 11, 2024

Язык: Английский

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New insights into the relationship of mitochondrial metabolism and atherosclerosis

Cellular Signalling, Год журнала: 2024, Номер 127, С. 111580 - 111580

Опубликована: Дек. 27, 2024

Язык: Английский

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Dimethyl Fumarate Mediates Sustained Vascular Smooth Muscle Cell Remodeling in a Mouse Model of Cerebral Aneurysm

Antioxidants, Год журнала: 2024, Номер 13(7), С. 773 - 773

Опубликована: Июнь 27, 2024

Cerebral aneurysms (CA) are a type of vascular disease that causes significant morbidity and mortality with rupture. Dysfunction the smooth muscle cells (VSMCs) from circle Willis (CoW) vessels mediates CA formation, as they major cell arterial wall play role in maintaining vessel integrity. Dimethyl fumarate (DMF), first-line oral treatment for relapsing-remitting multiple sclerosis, has been shown to inhibit VSMC proliferation reduce formation mouse model. Potential unwanted side effects DMF on function have not investigated yet. The present study characterizes impact using single-cell RNA-sequencing (scRNA-seq) CoW following induction further explores its mitochondrial vitro cultures. Two weeks impaired transcription glutathione redox system downregulated respiration genes VSMCs. In vitro, increased lactate enhanced production reactive oxygen species (ROS). These rendered VSMCs vulnerable oxidative stress led dysfunction enhancement apoptosis. Taken together, our data support concept DMF-mediated antiproliferative effect is linked disturbed antioxidative functions resulting altered metabolism. This negative may be preexisting alterations cerebrovascular due renal hypertension. Therefore, before severe adverse emerge, it would clinically relevant develop indices or biomarkers this monitor patients undergoing treatment.

Язык: Английский

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冠脉钙化与老年肿瘤患者的心血管病风险评估与干预

Scientia Sinica Vitae, Год журнала: 2024, Номер unknown

Опубликована: Авг. 1, 2024

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