Endothelial ZBTB16: a molecular shield against cardiac aging

Area of Science:

• Cardiovascular Biology
• Aging Research
• Epigenetics

Background:

• Aging increases cardiovascular disease risk via cardiac dysfunction.
• Endothelial cell (EC) impairment in aging is poorly understood.
• This study focuses on epigenetics in EC-dependent cardiac aging, highlighting ZBTB16.

Purpose of the Study:

• Investigate epigenetically regulated mechanisms of EC-dependent cardiac aging.
• Identify the role of zinc finger and BTB domain-containing protein 16 (ZBTB16) in cardiac aging.
• Determine if ZBTB16 can mitigate aging-associated cardiac dysfunction.

Main Methods:

• Chromatin accessibility (snATAC-seq) and transcriptomic (snRNA-seq) analyses of aged hearts.
• Functional studies using genetic models (Zbtb16 deletion, knockout) in mice.
• In vitro assays on EC senescence, secretory profiles, and effects of ZBTB16 deficiency.

Main Results:

• Aged hearts show reduced chromatin accessibility and ZBTB16 expression.
• Zbtb16 deletion in mice caused premature aging, diastolic dysfunction, and pro-fibrotic/inflammatory factor secretion.
• ZBTB16 overexpression reversed aging effects, reduced dysfunction, and suppressed nuclear receptor-interacting protein 1.

Conclusions:

• ZBTB16 maintains endothelial integrity and vascular niche homeostasis, protecting against cardiac aging.
• Loss of ZBTB16 promotes EC senescence and cardiac fibrosis.
• Restoring ZBTB16 expression is a potential therapeutic strategy for aging-related cardiovascular disease.