Aging-Associated ALKBH5-mA Modification Exacerbates Doxorubicin-Induced Cardiomyocyte Apoptosis Via AT-Rich Interaction Domain 2.

Background: Chemotherapy-induced cardiovascular disease is a growing concern in the elderly population who have survived cancer, yet the underlying mechanism remains poorly understood. We investigated the role of ALKBH5 (AlkB homolog 5), a primary N-methyladenosine (mA) demethylase, and its involvement in mA methylation-mediated regulation of targets in aging-associated doxorubicin-induced cardiotoxicity.

Methods And Results: To validate the relationship between doxorubicin-induced cardiotoxicity and aging, we established young and old male mouse models.

HMGB1 mediates homocysteine-induced endothelial cells pyroptosis via cathepsin V-dependent pathway.

Endothelial cells injury and pro-inflammation cytokines release are the initial steps of hyperhomocysteinemia (HHcy)-associated vascular inflammation. Pyroptosis is a newly identified pro-inflammation form of programmed cell death, causing cell lysis and IL-1β release, and characterized by the caspases-induced cleavage of its effector molecule gasdermins (GSDMs). However, the effect of homocysteine (Hcy) on endothelial cells pyroptosis and the underlying mechanisms have not been fully defined.

NRP1 regulates HMGB1 in vascular endothelial cells under high homocysteine condition.

Endothelial inflammation plays an important role in hyperhomocysteinemia (HHcy)-associated vascular diseases. High mobility group box 1 (HMGB1) is a pro-inflammatory danger molecule produced by endothelial cells. However, whether HMGB1 is involved in vascular endothelial inflammation of HHcy is poorly understood.

Silent Information Regulator 1 Negatively Regulates Atherosclerotic Angiogenesis via Mammalian Target of Rapamycin Complex 1 Signaling Pathway.

Background: This study aimed to investigate the interactions between silent information regulator 1 (SIRT1) and mammalian target of rapamycin (mTOR) in intraplaque angiogenesis and their potential mechanisms through in vivo and in vitro studies.

Methods: An atherosclerosis model was established in 12 rabbits on a high-cholesterol diet. The rabbits were equally divided into 3 groups: a control group (high-lipid diet), RAP group (high-lipid diet supplemented with rapamycin) and RAP + NAM group (high-lipid diet supplemented with rapamycin and nicotinamide).