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A recent study showed that peroxiredoxins (Prxs) play an important role in the development of pathological cardiac hypertrophy. However, the involvement of Prx5 in cardiac hypertrophy remains unclear. Therefore, this study is aimed at investigating the role and mechanisms of Prx5 in pathological cardiac hypertrophy and dysfunction. Transverse aortic constriction (TAC) surgery was performed to establish a pressure overload-induced cardiac hypertrophy model. In this study, we found that Prx5 expression was upregulated in hypertrophic hearts and cardiomyocytes. In addition, Prx5 knockdown accelerated pressure overload-induced cardiac hypertrophy and dysfunction in mice by activating oxidative stress and cardiomyocyte apoptosis. Importantly, heart deterioration caused by Prx5 knockdown was related to mitogen-activated protein kinase (MAPK) pathway activation. These findings suggest that Prx5 could be a novel target for treating cardiac hypertrophy and heart failure.

Background and Purpose. Abdominal aortic aneurysm (AAA) is a chronic inflammatory disorder and the important causes of death among men over the age of 65 years. Interleukin-12p35 (IL12p35) is an inflammatory cytokine that participates in a variety of inflammatory diseases. However, the role of IL12p35 in the formation and development of AAA is still unknown. Experimental Approach. Male apolipoprotein E-deficient (Apoe-/-) mice were generated and infused with 1.44 mg/kg angiotensin II (Ang II) per day. We found that IL12p35 expression was noticeably increased in the murine AAA aorta and isolated aortic smooth muscle cells (SMCs) after Ang II stimulation. IL12p35 silencing promoted Ang II-induced AAA formation and rupture in Apoe-/- mice. IL12p35 silencing markedly increased the expression of inflammatory cytokines, including IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), in both the serum and AAA aorta. Additionally, IL12p35 silencing exacerbated SMC apoptosis in Apoe-/- mice after Ang II infusion. IL12p35 silencing significantly increased signal transducer and activator of transcription (STAT) 4 phosphorylation levels in AAA mice, and STAT4 knockdown abolished the IL12p35-mediated proinflammatory response and SMC apoptosis. Interpretation. Silencing IL12p35 promotes AAA formation by activating the STAT4 pathway, and IL12p35 may serve as a novel and promising therapeutic target for AAA treatment.