ArticleProceedings of the National Academy of Sciences of the United States of America2021
Cyclic nucleotide phosphodiesterase 1C contributes to abdominal aortic aneurysm.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- MAPK14 converges on key transcriptional machinery to promote vascular smooth muscle cell degeneration in abdominal aortic aneurysm.Signal transduction and targeted therapy · 2026Article
- Sympathetic hyperinnervation drives abdominal aortic aneurysm development by promoting vascular smooth muscle cell phenotypic switching.Journal of advanced research · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- DNA methylation heterogeneity correlates with field cancerization and prognosis in lung adenocarcinoma patients.Clinical epigenetics · 2025Article
- Vinpocetine alleviates the abdominal aortic aneurysm progression via VSMCs SIRT1-p21 signaling pathway.Acta pharmacologica Sinica · 2025Article
- Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease.Korean circulation journal · 2024Article
- Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice.Nature communications · 2024Article
- Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice.npj aging · 2024Article
- Medium-Dose Formoterol Attenuated Abdominal Aortic Aneurysm Induced by EPO via β2AR/cAMP/SIRT1 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- 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
- Advances and challenges in regenerative therapies for abdominal aortic aneurysm.Frontiers in cardiovascular medicine · 2024Review
- Epidemiology, Symptoms and Pathophysiology of Long Covid Complications.Journal of cellular immunology · 2024Article
- Article
- SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence.Signal transduction and targeted therapy · 2023Article
- MicroRNA-19b-3p dysfunction of mesenchymal stem cell-derived exosomes from patients with abdominal aortic aneurysm impairs therapeutic efficacy.Journal of nanobiotechnology · 2023Article
- Emerging Role of cAMP/AMPK Signaling.Cells · 2022Review
- Cellular senescence and abdominal aortic aneurysm: From pathogenesis to therapeutics.Frontiers in cardiovascular medicine · 2022Review
- The Effects of Acute and Chronic Selective Phosphodiesterase 1 Inhibition on Smooth Muscle Cell-Associated Aging Features.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Abdominal aortic aneurysm (AAA) is characterized by aorta dilation due to wall degeneration, which mostly occurs in elderly males. Vascular aging is implicated in degenerative vascular pathologies, including AAA. Cyclic nucleotide phosphodiesterases, by hydrolyzing cyclic nucleotides, play critical roles in regulating vascular structure remodeling and function. Cyclic nucleotide phosphodiesterase 1C (PDE1C) expression is induced in dedifferentiated and aging vascular smooth muscle cells (SMCs), while little is known about the role of PDE1C in aneurysm. We observed that PDE1C was not expressed in normal aorta but highly induced in SMC-like cells in human and murine AAA. In mouse AAA models induced by Angiotensin II or periaortic elastase, PDE1C deficiency significantly decreased AAA incidence, aortic dilation, and elastin degradation, which supported a causative role of PDE1C in AAA development in vivo. Pharmacological inhibition of PDE1C also significantly suppressed preestablished AAA. We showed that PDE1C depletion antagonized SMC senescence in vitro and/or in vivo, as assessed by multiple senescence biomarkers, including senescence-associated β-galactosidase activity, γ-H2AX foci number, and p21 protein level. Interestingly, the role of PDE1C in SMC senescence in vitro and in vivo was dependent on Sirtuin 1 (SIRT1). Mechanistic studies further showed that cAMP derived from PDE1C inhibition stimulated SIRT1 activation, likely through a direct interaction between cAMP and SIRT1, which leads to subsequent up-regulation of SIRT1 expression. Our findings provide evidence that PDE1C elevation links SMC senescence to AAA development in both experimental animal models and human AAA, suggesting therapeutical significance of PDE1C as a potential target against aortic aneurysms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.