ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2015
Age-related decline of autocrine pituitary adenylate cyclase-activating polypeptide impairs angiogenic capacity of rat cerebromicrovascular endothelial cells.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 42 citations in OpenAlex.
- Protective Effects of PACAP in Diabetic Complications: Retinopathy, Nephropathy and Neuropathy.International journal of molecular sciences · 2025Review
- Diversity of Brain Microvascular Endothelial Cell Functions: Physiology, Ischemia/Hypoxia, and Underlying Protection.Aging and disease · 2025Review
- Review
- Article
- Plasma Somatostatin Levels Are Lower in Patients with Coronary Stenosis and Significantly Increase after Stent Implantation.Journal of clinical medicine · 2024Article
- Exploring the Role of Neuropeptide PACAP in Cytoskeletal Function Using Spectroscopic Methods.International journal of molecular sciences · 2024Article
- Downregulation of PACAP and the PAC1 Receptor in the Basal Ganglia, Substantia Nigra and Centrally Projecting Edinger-Westphal Nucleus in the Rotenone model of Parkinson's Disease.International journal of molecular sciences · 2023Article
- Role of endocrine PACAP in age-related diseases.Frontiers in endocrinology · 2023Review
- Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis.Frontiers in endocrinology · 2023Review
- Examination of pituitary adenylate cyclase-activating polypeptide in Parkinson's disease focusing on correlations with motor symptoms.GeroScience · 2022Article
- Hypertension-induced cognitive impairment: from pathophysiology to public health.Nature reviews. Nephrology · 2021Review
- Demonstration of age-related blood-brain barrier disruption and cerebromicrovascular rarefaction in mice by longitudinal intravital two-photon microscopy and optical coherence tomography.American journal of physiology. Heart and circulatory physiology · 2021Article
- Alterations of Nigral Dopamine Levels in Parkinson's Disease after Environmental Enrichment and PACAP Treatment in Aging Rats.Life (Basel, Switzerland) · 2021Article
- Time-restricted feeding (TRF) for prevention of age-related vascular cognitive impairment and dementia.Ageing research reviews · 2020Article
- Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke.Aging and disease · 2020Review
- Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain.GeroScience · 2020Article
- Protective Effects of PACAP in Peripheral Organs.Frontiers in endocrinology · 2020Review
- Article
- Role of endothelial NADAmerican journal of physiology. Heart and circulatory physiology · 2019Review
- Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment.American journal of physiology. Heart and circulatory physiology · 2019Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging.
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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.