Deficiency of peroxiredoxin 2 exacerbates angiotensin II-induced abdominal aortic aneurysm.
Se-Jin JeongMin Ji ChoNa Young KoSinai KimIn-Hyuk JungJeong-Ki MinSang Hak LeeJong-Gil ParkGoo Taeg OhPublished in: Experimental & molecular medicine (2020)
Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease characterized by structural deterioration of the aorta caused by inflammation and oxidative stress, leading to aortic dilatation and rupture. Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, has been reported as a potential negative regulator of inflammatory vascular diseases, and it has been identified as a protein that is increased in patients with ruptured AAA compared to patients with nonruptured AAA. In this study, we demonstrated that PRDX2 was a pivotal factor involved in the inhibition of AAA progression. PRDX2 levels were increased in AAA compared with those in normal aortas in both humans and mice. Ultrasound imaging revealed that the loss of PRDX2 accelerated the development of AAA in the early stages and increased AAA incidence in mice infused with angiotensin II (Ang II). Prdx2-/- mice infused with Ang II exhibited increased aortic dilatation and maximal aortic diameter without a change in blood pressure. Structural deterioration of the aortas from Prdx2-/- mice infused with Ang II was associated with increases in the degradation of elastin, oxidative stress, and intramural thrombi caused by microhemorrhages, immature neovessels, and the activation of matrix metalloproteinases compared to that observed in controls. Moreover, an increase in inflammatory responses, including the production of cell adhesion molecules and the accumulation of inflammatory cells and proinflammatory cytokines due to PRDX2 deficiency, accelerated Ang II-induced AAA progression. Our data confirm that PRDX2 plays a role as a negative regulator of the pathological process of AAA and suggest that increasing PRDX2 activity may be a novel strategy for the prevention and treatment of AAA.
Keyphrases
- pulmonary arterial hypertension
- angiotensin ii
- pulmonary artery
- oxidative stress
- abdominal aortic aneurysm
- pulmonary hypertension
- diabetic rats
- angiotensin converting enzyme
- vascular smooth muscle cells
- induced apoptosis
- high fat diet induced
- aortic valve
- blood pressure
- left ventricular
- ischemia reperfusion injury
- heart rate
- dna damage
- insulin resistance
- cell adhesion
- transcription factor
- type diabetes
- small molecule
- cell death
- endoplasmic reticulum stress
- brain injury
- climate change
- aortic dissection
- heat shock
- protein protein
- atrial fibrillation
- heat shock protein
- optical coherence tomography
- electronic health record