Cardiac Autophagy in Sepsis

Abstract

Sepsis is a leading cause of death in intensive care units, and cardiac dysfunction is an identified serious component of the multi-organ failure associated with this critical condition. This review summarized the current discoveries and hypothesizes of how autophagy changes in the heart during sepsis and the underlying mechanisms. Recent investigations suggest that specific activation of autophagy initiation factor Beclin-1 has a potential to protect cardiac mitochondria, attenuate inflammation, and improve cardiac function in sepsis. Accordingly, pharmacological interventions targeting this pathway have a potential to become an effective approach to control sepsis outcomes. The role of autophagy during sepsis pathogenesis has been under intensive investigation in recent years. It is expected that developing therapeutic approaches with specificities targeting at autophagy regulatory factors may provide new opportunities to alleviate organ dysfunction caused by maladaptive autophagy during sepsis.

CD74 knockout protects against LPS‐induced myocardial contractile dysfunction through AMPK‐Skp2‐SUV39H1‐mediated demethylation of BCLB

“…Although antioxidants (such as metallothionein, insulin-like growth factor I and catalase), mitochondrial protein aldehyde dehydrogenase (ALDH2) and ER chaperones have shown some promise in the treatment of septic cardiomyopathy (Ceylan-Isik et al, 2010;Durand et al, 2017;Pang, Peng et al, 2019;Turdi et al, 2012), clinical validation has not been consolidated for antioxidants and mitochondrial drugs in sepsis and septic hearts. More recent findings from our group and others depicted a rather pivotal role for autophagy dysregulation in the onset and development of septic cardiomyopathy (Pang, Peng, et al, 2019;Pang, Zheng, et al, 2019;Piquereau et al, 2013;Ren et al, 2016;Sun et al, 2018), although the mechanism behind sepsis-induced autophagy dysregulation is still unclear.…”

“…CD74 is a non‐polymorphic type II transmembrane glycoprotein, participating in T‐cell and B‐cell development, dendritic cell motility and macrophage inflammation in inflammatory diseases including liver fibrosis, diabetes mellitus, systemic lupus erythematosus and Alzheimer disease (Su, Na, Zhang, & Zhao, ). Given the important role of autophagy, oxidative stress and inflammation in septic hearts (Ren et al, ; Sun et al, ; Sun, Cai, & Zang, ), levels of autophagy, O 2 − production, apoptosis and proinflammatory markers were monitored in WT and Cd74 −/− mice challenged with LPS. Levels of key autophagy regulatory molecules including Akt, AMP‐dependent protein kinase (AMPK) and mTOR were evaluated in murine hearts.…”

Dexmedetomidine Protects Against Lipopolysaccharide-Induced Acute Kidney Injury by Enhancing Autophagy Through Inhibition of the PI3K/AKT/mTOR Pathway

“…Autophagy is a mechanism which recycles damaged organelles and cellular components in response to various stress conditions such as nutrient deprivation (Filomeni et al, 2015), metabolic balance (Maiuri et al, 2007), apoptosis (Maiuri et al, 2007) and inflammation (Kimura et al, 2017), and is beneficial for cell survival. Clinical and preclinical studies confirm that sepsis triggers autophagy in multiple organs, including the kidney (Wan et al, 2016;Chung et al, 2017;Kimura et al, 2017;Sun et al, 2019), and an increasing amount of evidence suggests that stimulating autophagy via pharmacological approaches protects the kidney during sepsis (Mei et al, 2016). Mitophagy, the selective removal of mitochondria by autophagy, also plays an important role in SAKI (Kaushal and Shah, 2016).…”

Identification of mitochondrial function‐associated lncRNAs in septic mice myocardium

“…The pathogenesis of septic cardiomyopathy might be involved in the inflammatory cascade, activation of nitric oxide synthase, metabolic remodeling and oxidative stress 3‐5 . Mitochondrial dysfunction is the key event of myocardium damage during sepsis 6,7 …”