Related Experiment Video
Updated: Dec 9, 2025
Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System
Published on: October 22, 2020
Beclin1 Haploinsufficiency accentuates second-hand smoke exposure -induced myocardial Remodeling and contractile
Fangpeng Liu1, Yandong Liu2, Zhiqiang Zhuang3
1Department of Respiration, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
Abstract:
Second-hand smoking evokes inflammation and cardiovascular diseases. Recent evidence has revealed a pivotal role for deranged autophagy in smoke exposure-induced cardiac anomalies. This study evaluated the impact of haploinsufficiency of the mTOR-independent autophagy protein Beclin1 on side-stream smoke exposure-induced cardiac anomalies and mechanism(s) involved. Adult WT and Beclin1 haploinsufficiency (Becn+/-) mice were exposed to cigarette smoke for 1 h daily for 90 days. Echocardiographic, cardiomyocyte function, intracellular Ca2+, autophagy, mitophagy, apoptosis and inflammation were examined. DHE staining was employed to evaluate O2- level. Our data revealed that Beclin1 deficiency exacerbated smoke exposure-induced myocardial anomalies in geometry, fractional shortening, cardiomyocyte function, intracellular Ca2+ handling, TEM ultrastructure, and inflammation along with pronounced apoptosis and O2- production. Side-stream smoke provoked excessive autophagy/mitophagy, mtDNA release, and activation of innate immune response signals cyclic GMP-AMP synthase (cGAS) and its effector - stimulator of interferon genes (STING), the effect was abolished or unaffected by Becn haploinsufficiency. STING phosphorylation was overtly promoted by smoke exposure in Becn+/- mice. Smoke exposure also suppressed phosphorylation of mTOR although it facilitated that of ULK1 in both groups. In vitro data revealed that inhibition of cGAS or STING failed to affect smoke extract-induced mitophagy although they abrogated smoke extract-induced cardiomyocyte dysfunction except cGAS inhibition in Becn+/- mice. These data suggest that Beclin1 is integral in the maintenance of cardiac homeostasis under side-stream smoke exposure via a STING-mediated mechanism.
Insights
Beclin1 deficiency worsens heart damage from secondhand smoke by disrupting cellular repair pathways and increasing inflammation. This highlights Beclin1
Area of Science:
- Cardiovascular Biology
- Cellular Autophagy
- Toxicology
Background:
- Secondhand smoke exposure is a significant risk factor for cardiovascular diseases.
- Autophagy, a cellular recycling process, plays a critical role in maintaining cardiac health, and its derangement is implicated in smoke-induced cardiac anomalies.
- Beclin1 is a key protein regulating mTOR-independent autophagy, crucial for cellular homeostasis.
Purpose of the Study:
- To investigate the impact of Beclin1 haploinsufficiency on cardiac anomalies induced by side-stream smoke exposure.
- To elucidate the underlying mechanisms, including autophagy, mitophagy, apoptosis, inflammation, and innate immune signaling, involved in smoke-induced cardiac dysfunction.
- To determine the role of Beclin1 in mediating cardiac protection against environmental toxins.
Main Methods:
- Adult wild-type (WT) and Beclin1 haploinsufficiency (Becn+/-) mice were exposed to cigarette smoke daily for 90 days.
- Cardiac function was assessed using echocardiography and cardiomyocyte contractility measurements.
- Mechanistic investigations included analysis of intracellular calcium handling, autophagy/mitophagy markers, apoptosis, oxidative stress (O2-), and innate immune signaling pathways (cGAS-STING).
Main Results:
- Beclin1 deficiency exacerbated smoke-induced cardiac anomalies, including impaired geometry, reduced fractional shortening, and compromised cardiomyocyte function.
- Smoke exposure led to increased apoptosis, oxidative stress, and inflammation in Becn+/- mice compared to WT.
- While smoke induced excessive autophagy/mitophagy and activated cGAS-STING signaling, Beclin1 haploinsufficiency modulated STING phosphorylation and partially affected smoke-induced cardiomyocyte dysfunction, suggesting a complex interplay.
- Inhibition of cGAS or STING abrogated smoke extract-induced cardiomyocyte dysfunction, except in Becn+/- mice, indicating Beclin1's role in this pathway.
Conclusions:
- Beclin1 haploinsufficiency significantly worsens cardiac dysfunction and pathology induced by secondhand smoke exposure.
- The STING-mediated innate immune response is a key mechanism through which Beclin1 influences cardiac homeostasis during smoke exposure.
- These findings underscore the protective role of Beclin1 in maintaining cardiac health against environmental insults like secondhand smoke.
Related Concept Videos
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation
01:21Myocarditis I: Introduction
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...