Abstract
Abdominal aortic aneurysms (AAAs) are a progressive dilation of the aorta that is characterized by an initial influx of inflammatory cells followed by a pro‐inflammatory, migratory, proliferative, and eventually apoptotic smooth muscle cell phenotype. In recent years, the mechanisms related to the initial influx of inflammatory cells have become well‐studied; the mechanisms related to chronic aneurysm formation, smooth muscle cell apoptosis and death are less well‐characterized. Autophagy is a generally believed to be a protective cellular mechanism that functions to recycle defective proteins and cellular organelles to maintain cellular homeostasis. Our goal with the present study was to investigate the role of autophagy in smooth muscle cells during AAA formation. Levels of the autophagy factors, Beclin, and LC3 were elevated in human and mouse AAA tissue via both qPCR and immunohistochemical analysis. Confocal staining in human and mouse AAA tissue demonstrated Beclin and LC3 were present in smooth muscle cells during AAA formation. Treatment of smooth muscle cells with porcine pancreatic elastase or interleukin (IL)‐1β activated autophagy‐related genes in vitro while treatment with a siRNA to Kruppel‐like transcription factor 4 (Klf4), Kruppel‐like transcription factor 2 (Klf2) or Zinc‐finger protein 148 (Zfp148) separately inhibited activation of autophagy genes. Chromatin immunoprecipitation assays demonstrated that Klf4, Klf2, and Zfp148 separately bind autophagy genes in smooth muscle cells following elastase treatment. These results demonstrate that autophagy is an important mechanism related to Klfs in smooth muscle cells during AAA formation.
Highlights
Abdominal aortic aneurysms (AAA) remain a major healthcare concern in the United States because they are a gender-specific disease that targets men 4:1 over women
Few studies have investigated the role of autophagy in AAA formation and in smooth muscle cells during the formation of the disease (Ramadan et al 2015, 2017a,b)
Few studies have investigated the role of autophagy in AAA formation; we sought to establish whether AAA formation leads to increases in autophagy
Summary
Abdominal aortic aneurysms (AAA) remain a major healthcare concern in the United States because they are a gender-specific disease that targets men 4:1 over women P., and the National Center for Injury Prevention and Control, WISQARS 2007; Kent et al 2010; Hoyert and Xu 2012; Bhak et al 2014). AAAs are especially concerning as they are asymptomatic, difficult to diagnose, and rupture results in a high-mortality rate, resulting in AAAs being the 15th leading cause of death in the aging population. As Western populations continue to age, these numbers will continue to increase until better methods to diagnose and treat aneurysms are identified P., and the National Center for Injury Prevention and Control, WISQARS 2007; Kent et al 2010; Hoyert and Xu 2012;
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