Beclin-1-dependent autophagy protects perivascular adipose tissue function from hyperaldosteronism effects

Area of Science:

• Cardiovascular Physiology
• Metabolic Research
• Cellular Biology

Background:

• Hyperaldosteronism (HA) causes cardiovascular damage and perivascular adipose tissue (PVAT) dysfunction.
• Aldosterone (Aldo) is known to impair autophagy in various tissues.
• The specific role of Beclin-1 (BCN1)-dependent autophagy in PVAT under HA remains unclear.

Purpose of the Study:

• To investigate whether HA impairs autophagic flux in PVAT via BCN1.
• To determine if BCN1-dependent autophagy protects PVAT from inflammation and dysfunction.
• To explore the therapeutic potential of activating BCN1-dependent autophagy in HA.

Main Methods:

• Aldosterone infusion in wild-type and BCN1 knock-in mice.
• Assessment of vascular function, blood pressure, PVAT inflammation, and oxidative stress.
• Pharmacological modulation of autophagy using spermidine and TB peptide.

Main Results:

• HA disrupted PVAT autophagic flux, reduced BCN1 activity, and impaired PVAT's anticontractile function in wild-type mice.
• BCN1 knock-in mice were protected from PVAT dysfunction and inflammation, showing preserved homeostasis.
• Pharmacological autophagy activation improved PVAT function, and BCN1 knock-in mice showed partial protection against hypertension.

Conclusions:

• Activation of autophagy, particularly BCN1-dependent pathways, protects against HA-induced PVAT inflammation, dysfunction, and hypertension.
• Disrupted autophagy in PVAT contributes to oxidative stress and vascular dysfunction in HA.
• Targeting BCN1-dependent autophagy represents a promising therapeutic strategy for mitigating cardiovascular effects of HA.