G6PD-deficiency Mitigates Gender-dependent Differences in the Aortic Stiffness in Rats

Gender-dependent differences in vascular function and blood pressure in humans and animals are well known. However, the pathogenesis of aortic stiffness is not well characterized and the mechanism(s) that enhances aortic stiffness in males vs females are still unclear. The objective of this study was to: 1) investigate the possibility of differences in aortic stiffness between age-matched male and female rats: and 2) determine the mechanism(s) that mediate aortic stiffness in a gender-dependent manner. We determined aortic stiffness in glucose-6-phosphate dehydrogenase (G6PD, a X chromosome-linked enzyme, involved in glucose metabolism)-deficient and wild-type (WT) rats by 2D-echocardiography and quantified the expression of genes encoding the key factor(s) implicated in the pathogenesis of aortic stiffness, such as lysine oxidase (LOX); inflammatory cytokines and chemokines; and plasminogen activator inhibitor-1 (PAI-1), by qPCR and Western blot analyses. Our results revealed significantly lower aortic stiffness in WT-female rats than in WT-male rats. Next, we found significantly (p<0.05) lower expression of genes encoding LOX, CCL5, and PAI-1, respectively, in the aorta of WT-female as compared to WT-male rats. Interestingly, significant down-regulation in the expression of Lox, Ccl5 and Serpine1 genes was observed in the G6PD-deficienct male rats, suggesting that G6PD mitigated the gender-dependent differences in aortic stiffness in the rats. Taken together, these findings indicate that G6PD-dependent higher expression of LOX, CCL5, and PAI-1, in the aorta of male rats contributed to the higher stiffness in male than in the female rats. Supported by NHLBI (5R01HL166546) grant to SAG This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.