TY - JOUR
T1 - Unravelling the impact of aging on the human endothelial lncRNA transcriptome
AU - Drekolia, Maria-Kyriaki
AU - Talyan, Sweta
AU - Cordellini Emídio, Rebeca
AU - Boon, Reinier Abraham
AU - Guenther, Stefan
AU - Looso, Mario
AU - Dumbović, Gabrijela
AU - Bibli, Sofia-Iris
N1 - Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (CRC1366, Project B1 to S-IB; the Emmy Noether Programme BI 2163/1-1 to S-IB; the Johanna Quandt Young Academy at Goethe to S-IB; the Cardio-Pulmonary Institute, EXC 2026, Project ID: 390649896 to S-IB, GD, and ML; SB TRR267, Project-ID 403584255 to GD and RB). M-KD was supported with a scholarship from Onassis Foundation. Publisher Copyright: Copyright © 2022 Drekolia, Talyan, Cordellini Emídio, Boon, Guenther, Looso, Dumbović and Bibli.
PY - 2022/10/21
Y1 - 2022/10/21
N2 - The incidence and prevalence of cardiovascular disease is highest among the elderly. There is a need to further understand the mechanisms behind endothelial cell aging in order to achieve vascular rejuvenation and minimize the onset of age-related vascular diseases. Long non-coding RNAs (lncRNAs) have been proposed to regulate numerous processes in the human genome, yet their function in vascular aging and their therapeutic potential remain largely unknown. This is primarily because the majority of studies investigating the impact of aging on lncRNA expression heavily rely on in vitro studies based on replicative senescence. Here, using a unique collection of young and aged endothelial cells isolated from native human arteries, we sought to characterize the age-related alterations in lncRNA expression profiles. We were able to detect a total of 4463 lncRNAs expressed in the human endothelium from which ∼17% (798) were altered in advanced age. One of the most affected lncRNAs in aging was the primate-specific, Prostate Cancer Associated Transcript (PCAT) 14. In our follow up analysis, using single molecule RNA FISH, we showed that PCAT14 is relatively abundant, localized almost exclusively in the nucleus of young endothelial cells, and silenced in the aged endothelium. Functionally, our studies proposed that downregulation of PCAT14 alters endothelial cell transcription profile and cell functions including endothelial cell migration, sprouting and inflammatory responses in vitro. Taken together, our data highlight that endothelial cell aging correlates with altered expression of lncRNAs, which could impair the endothelial regenerative capacity and enhance inflammatory phenotypes.
AB - The incidence and prevalence of cardiovascular disease is highest among the elderly. There is a need to further understand the mechanisms behind endothelial cell aging in order to achieve vascular rejuvenation and minimize the onset of age-related vascular diseases. Long non-coding RNAs (lncRNAs) have been proposed to regulate numerous processes in the human genome, yet their function in vascular aging and their therapeutic potential remain largely unknown. This is primarily because the majority of studies investigating the impact of aging on lncRNA expression heavily rely on in vitro studies based on replicative senescence. Here, using a unique collection of young and aged endothelial cells isolated from native human arteries, we sought to characterize the age-related alterations in lncRNA expression profiles. We were able to detect a total of 4463 lncRNAs expressed in the human endothelium from which ∼17% (798) were altered in advanced age. One of the most affected lncRNAs in aging was the primate-specific, Prostate Cancer Associated Transcript (PCAT) 14. In our follow up analysis, using single molecule RNA FISH, we showed that PCAT14 is relatively abundant, localized almost exclusively in the nucleus of young endothelial cells, and silenced in the aged endothelium. Functionally, our studies proposed that downregulation of PCAT14 alters endothelial cell transcription profile and cell functions including endothelial cell migration, sprouting and inflammatory responses in vitro. Taken together, our data highlight that endothelial cell aging correlates with altered expression of lncRNAs, which could impair the endothelial regenerative capacity and enhance inflammatory phenotypes.
KW - PCAT14
KW - aging
KW - endothelium
KW - lncRNA
KW - regeneration
UR - http://www.scopus.com/inward/record.url?scp=85141402954&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fgene.2022.1035380
DO - https://doi.org/10.3389/fgene.2022.1035380
M3 - Article
C2 - 36338971
SN - 1664-8021
VL - 13
JO - Frontiers in genetics
JF - Frontiers in genetics
M1 - 1035380
ER -