Inhibition of Development of Abdominal Aortic Aneurysm by Glycolysis Restriction

Abstract

Objective-The mechanisms underlying abdominal aortic aneurysm development remain unknown. We hypothesized that acceleration of glucose metabolism with the upregulation of glucose transporters is associated with abdominal aortic aneurysm development. Methods and Results-Enhanced accumulation of the modified glucose analogue 18 fluoro-deoxyglucose by positron emission tomography imaging in the human abdominal aortic aneurysm was associated with protein expressions of glucose transporters-1 and -3, assessed by Western blot. The magnitude of glucose transporter-3 expression was correlated with zymographic matrix metalloproteinase-9 activity. Intraperitoneal administration of glycolysis inhibitor with 2-deoxyglucose significantly attenuated the dilatation of abdominal aorta induced by periaortic application of CaCl 2 in C57BL/6J male mice or reduced the aneurysmal formation in angiotensin II-infused apolipoprotein E knockout male mice. In monocytic cell line induced by phorbol 12-myristate 13-acetate or ex vivo culture obtained from human aneurysmal tissues, 2-deoxyglucose abrogated the matrix metalloproteinase-9 activity and interleukin-6 expression in these cells/tissues. Moreover, 2-deoxyglucose attenuated the survival/proliferation of monocytes and the adherence of them to vascular endothelial cells. Conclusion-This study suggests that the enhanced glycolytic activity in aortic wall contributes to the pathogenesis of aneurysm development. In addition, pharmacological intervention in glycolytic activity might be a potential therapeutic target for the disorder.

Altered PPARγ Coactivator-1 Alpha Expression in Abdominal Aortic Aneurysm: Possible Effects on Mitochondrial Biogenesis

“…Although the expression of mitochondrial proteins has not previously been investigated in human AAA, an enhanced glycolytic activity and ROS production in the aortic wall has been suggested to contribute to the pathogenesis of aneurysm development [16,17,18]. Glycolysis is a metabolic process restricted to the cytosol of the cell.Our finding that PGC1α, TFAM and VDAC expression was reduced in AAA supports the hypothesis that reduced mitochondrial activity is involved in the pathogenesis of AAA.…”

High glucose and interleukin 1β-induced apoptosis in human umbilical vein endothelial cells involves in down-regulation of monocarboxylate transporter 4

“…Recently, Bock et al demonstrated that glycolysis is a major source of ATP in ECs. The glycolysis activity of ECs is closely related to cell function, such as proliferation [9], migration [9,23] and adherence [24]. Lactate is the final product of glycolysis and regulates glycolysis and intracellular pH.…”

Selective Targeting of the Cysteine Proteome by Thioredoxin and Glutathione Redox Systems

“…The differences in time courses of ARF and BSO and variability in detection of the C 62 that the observed effects may not be limited to the Trx system. The longer time frame for BSO treatment could allow changes because of transcriptional activation as shown previously by Harris et al (27).…”

“…This could be important in conditions of energy limitation, such as can occur during development and tissue repair (61,62), where oxidation could impair development or tissue repair and recovery. Conversely, enhanced dependence on glycolytic energy metabolism occurs in cancer, a characteristic previously developed as a therapeutic approach for cancer treatment (63).…”