Premium
Age‐Related Decline of Autocrine Pituitary Adenylate Cyclase‐Activating Polypeptide Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells
Author(s) -
Banki Eszter,
Sosnowska Danuta,
Tucsek Zsuzsanna,
Gautam Tripti,
Toth Peter,
Tarantini Stefano,
Tamas Andrea,
Helyes Zsuzsanna,
Reglodi Dora,
Sonntag William,
Csiszar Anna,
Ungvari Zoltan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.630.3
Subject(s) - autocrine signalling , paracrine signalling , angiogenesis , microbiology and biotechnology , endocrinology , medicine , pituitary adenylate cyclase activating peptide , gene knockdown , apoptosis , biology , adenylate kinase , neuropeptide , chemistry , vasoactive intestinal peptide , receptor , biochemistry
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 conferring important antiaging effects. We hypothesized that age‐related changes in autocrine PACAP signaling contributes to impaired angiogenic capacity. Primary CMVECs were isolated from young (3 mo) and aged (24 mo) F344xBN rats. Expression of PACAP was decreased in aged cells associated with impaired capacity to form capillary‐like structures, adhesiveness to collagen (ECIS technology), and increased apoptosis (caspase3). PACAP overexpression in aged cells resulted in increased capillary‐like structure formation. Treatment with recombinant PACAP significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young cells shRNA knockdown of PACAP expression impaired tube formation, mimicking the aging phenotype. Cellular (DHE) and mitochondrial (MitoSox) ROS production increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age‐related dysregulation of PACAP signaling may contribute to impaired angiogenic capacity of aged CMVECs.