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

Hyperaldosteronism (HA), characterized by excessive production of aldosterone (Aldo), contributes to cardiovascular damage and perivascular adipose tissue (PVAT) dysfunction. Previous studies have shown that Aldo can impair autophagy in various tissues. However, it remains unclear whether this impairment occurs specifically in PVAT and whether it involves disruption of autophagic flux through Beclin-1 (BCN1), a key regulator of autophagosome formation and maturation. We hypothesize that BCN1-dependent autophagy plays a protective role in PVAT by limiting inflammation and preserving its anticontractile function in the context of HA. Male and female C57BL/6J [wild type (WT)] and BCN1 knock-in mice, aged 10-12 wk, underwent 14-day aldosterone infusion (600 µg/kg/day) using an osmotic minipump. Vascular function was assessed in PVAT-intact thoracic aortae, and blood pressure was monitored via radiotelemetry. HA disrupted PVAT autophagic flux, leading to the accumulation of LC3II/I and p62 proteins and reduced BCN1 expression/activity. In WT mice, PVAT exhibited an anticontractile effect, which was abolished by HA. In contrast, BCN1-knock-in mice were protected from this loss of PVAT function. HA also induced oxidative stress and inflammation in PVAT, as evidenced by increased reactive oxygen species generation and elevated mRNA levels of TNF-α, IL-6, IL-1β, and IL-17. These proinflammatory and prooxidative changes were not observed in BCN1-knock-in mice, indicating preserved PVAT homeostasis. Furthermore, pharmacological induction of autophagy via spermidine and activation of BCN1 with TB peptide improved PVAT function in HA-treated WT mice. Finally, BCN1-knock-in mice exhibited partial protection against HA-induced hypertension, highlighting the systemic vascular benefits of enhanced autophagic flux. In summary, our findings demonstrate that the activation of autophagy provides protection against HA-induced PVAT inflammation, dysfunction, and hypertension. Consequently, the activation of BCN1 could serve as a pharmacological strategy to prevent the harmful cardiovascular effects associated with HA.<b>NEW & NOTEWORTHY</b> Elevated aldosterone levels, as seen in primary hyperaldosteronism, obesity, and hypertension, impair autophagic flux in perivascular adipose tissue (PVAT), leading to increased inflammation and loss of anticontractile function. The Beclin-1-dependent autophagic pathway plays a key role in maintaining PVAT homeostasis and vascular tone. Disrupted autophagy contributes to oxidative stress and hypertension. Activating this pathway may offer a novel therapeutic strategy to mitigate aldosterone's harmful vascular effects in hypertension by restoring PVAT function and vascular inflammation.