BRD7 mediates hyperglycaemia-induced myocardial apoptosis via endoplasmic reticulum stress signalling pathway

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Endocrinology

Background:

• Diabetic cardiomyopathy (DCM) involves endoplasmic reticulum (ER) stress-induced apoptosis, but the underlying mechanisms remain unclear.
• Bromodomain-containing protein 7 (BRD7) is a tumor suppressor regulating apoptosis and cell cycle.
• The role of BRD7 in high glucose (HG)-induced cardiomyocyte apoptosis in DCM is not well understood.

Purpose of the Study:

• To investigate the role of BRD7 in high glucose (HG)-induced apoptosis of cardiomyocytes.
• To elucidate the molecular mechanism by which BRD7 influences ER stress and apoptosis in the context of hyperglycemia.

Main Methods:

• A type 1 diabetic rat model was established using streptozotocin (STZ).
• Lentivirus-mediated short hairpin RNA (shRNA) was used to inhibit BRD7 expression in vivo and in vitro (H9c2 cardiomyoblasts).
• Key molecular markers of ER stress (XBP-1s, CHOP) and apoptosis were assessed.

Main Results:

• Diabetic rats exhibited myocardial remodeling, fibrosis, cardiac dysfunction, and apoptosis, with up-regulated BRD7 expression.
• BRD7 inhibition ameliorated diabetes-induced heart damage.
• High glucose treatment increased BRD7 levels, activated ERK1/2, and promoted ER stress-induced apoptosis via XBP-1s and CHOP.
• Down-regulating BRD7 attenuated HG-induced CHOP expression by inhibiting XBP-1s nuclear translocation.

Conclusions:

• BRD7 plays a critical role in high glucose-induced cardiomyocyte apoptosis.
• Inhibition of BRD7 protects against hyperglycemia-induced cardiac damage by suppressing the ER stress signaling pathway.
• Targeting BRD7 may represent a novel therapeutic strategy for diabetic cardiomyopathy.