ArticleAntioxidants (Basel, Switzerland)2021
Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA.
Article in Antioxidants (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- The perspective of cAMP/cGMP signaling and cyclic nucleotide phosphodiesterases in aortic aneurysm and dissection.Vascular pharmacology · 2024Review
- PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets.International journal of molecular sciences · 2023Review
- Novel pharmacological approaches in abdominal aortic aneurysm.Clinical science (London, England : 1979) · 2023Review
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Role of the renin-angiotensin system in NETosis in the coronavirus disease 2019 (COVID-19).Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Human Lysyl Oxidase Over-Expression Enhances Baseline Cardiac Oxidative Stress but Does Not Aggravate ROS Generation or Infarct Size Following Myocardial Ischemia-Reperfusion.Antioxidants (Basel, Switzerland) · 2021Article
- Oxidative Stress in Vascular Pathophysiology: Still Much to Learn.Antioxidants (Basel, Switzerland) · 2021Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Abdominal aortic aneurysm (AAA) is a common life-threatening condition characterized by exacerbated inflammation and the generation of reactive oxygen species. Pharmacological treatments to slow AAA progression or to prevent its rupture remain a challenge. Targeting phosphodiesterase 4 (PDE4) has been verified as an effective therapeutic strategy for an array of inflammatory conditions; however, no studies have assessed yet PDE4 in AAA. Here, we used angiotensin II (AngII)-infused apolipoprotein E deficient mice to study the involvement of the PDE4 subfamily in aneurysmal disease. PDE4B but not PDE4D was upregulated in inflammatory cells from both experimental and human AAA. The administration of the PDE4 selective inhibitor rolipram (3 mg/kg/day) to AngII-challenged mice (1000 ng/kg bodyweight/min) protected against AAA formation, limiting the progressive increase in the aortic diameter without affecting the blood pressure. The drug strongly attenuated the rise in vascular oxidative stress (superoxide anion) induced by AngII, and decreased the expression of inflammatory markers, as well as the recruitment of macrophages (MAC3+), lymphocytes (CD3+), and neutrophils (ELANE+) into the vessel wall. Rolipram also normalized the vascular MMP2 expression and MMP activity, preserving the elastin integrity and improving the vascular remodelling. These results point to PDE4B as a new therapeutic target for AAA.
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