Chronic HDAC6 Activation Induces Atrial Fibrillation Through Atrial Electrical and Structural Remodeling in...

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Pathophysiology

Background:

• Atrial fibrillation (AF) is a common complication of hypertension.
• Hypertension is known to induce cardiac Histone Deacetylase 6 (HDAC6) catalytic activity.
• The specific role of HDAC6 activation in hypertension-induced AF remains unclear.

Purpose of the Study:

• To investigate whether chronic cardiac HDAC6 activation leads to atrial remodeling and AF induction.
• To examine the effects of HDAC6 activation on atrial electrical and structural properties.

Main Methods:

• Created HDAC6 constitutively active transgenic (TG) mice overexpressing active HDAC6 in cardiomyocytes.
• Compared AF induction, atrial conduction velocity, atrial size, interstitial fibrosis, connexin expression, and interleukin 6 gene expression between HDAC6 active TG and non-transgenic (NTG) mice.
• Utilized left atrial burst pacing and steady-state atrial pacing protocols.

Main Results:

• HDAC6 active TG mice exhibited a significantly higher frequency of sustained AF compared to NTG mice.
• Atrial conduction velocity was decreased, and atrial interstitial fibrosis was increased in HDAC6 active TG mice.
• Heterogeneous distribution of CX40 and CX43, and increased interleukin 6 gene expression were observed in HDAC6 active TG atria.

Conclusions:

• Chronic cardiac HDAC6 activation induces atrial electrical and structural remodeling.
• HDAC6 activation contributes to sustained atrial fibrillation.
• HDAC6 catalytic activity in hypertension may be a critical factor in AF development.