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Ketosis Prevents Abdominal Aortic Aneurysm Progression and Rupture in Male Rats

Open AccessPublished:June 10, 2022DOI:https://doi.org/10.1016/j.jvssci.2022.05.027

      Background

      Abdominal aortic aneurysms (AAA) are common in aging populations, and its rupture is associated with high mortality. There is no effective medical therapy for the prevention of AAA expansion and rupture. Ketone bodies (KB) are argued to produce novel responses against injury. Serum KB are elevated through a ketogenic diet (KD) or the intake of exogenous KB (EKB). We hypothesize that ketosis can reduce AAA expansion and risk of rupture.

      Methods

      Male Sprague-Dawley rats underwent intraluminal exposure to porcine pancreatic elastase to induce AAA formation. Rats were also administered daily β-aminopropionitrile to promote AAA rupture. Control rats (n = 12) were fed a standard diet (SD). Treated rats were given either a KD (n = 9) or EKB (n = 10) starting 3 days after AAA induction. Ketosis was verified by blood beta-hydroxybutyrate level of greater than 0.5 mmol/L. The in vivo aortic diameter was evaluated by ultrasound examination.

      Results

      After 2 weeks, surviving animals were harvested, and AAA tissue analysis was performed. Rupture AAA was determined by necropsy. Rats treated with KD consistently remained in ketosis, while rats treated with EKB remained in ketosis for only 8 hours per day. AAA size was significantly reduced (P < .01 and P < .05) in both KD and EKB groups at weeks 1 and 2. Rupture rate was also reduced in the KD and EKB groups (22% and 40%, respectively) compared with 67% in the SD group (P = .03 and .12, respectively). AAA trichrome staining demonstrated greater content of collagen in KD and EKB groups when compared with SD group (P = .08 and .02, respectively). AAA gelatin zymography demonstrated significantly decreased active matrix metalloproteinase (MMP)-9 levels in the KD and EKB groups (P < .05) while total MMP-2 was attenuated in the KD group (P < .01). Ketosis appears to reduce AAA expansion and risk of rupture. This may have resulted from AAA increased collagen deposition as well as decreased MMP activity. These findings provide initial impetus to investigate whether ketosis in patients with small AAAs can prevent expansion and risk of rupture.
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