MOLECULAR AND CELLULAR CHANGES IN ARTERIAL FUNCTION OVER THE LIFE COURSE – FROM ACCELERATED AGEING TO CALCIFICATION
Vascular stiffening and calcification are hallmarks of ageing and these pathologies are accelerated in patients with diabetes and renal failure. Emerging evidence has defined a role for nuclear lamina defects and the DNA damage response in driving vascular calcification. The mechanisms responsible a...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-12-01
|
| Series: | Artery Research |
| Online Access: | https://www.atlantis-press.com/article/125929980/view |
| _version_ | 1818229989669076992 |
|---|---|
| author | Catherine M. Shanahan |
| author_facet | Catherine M. Shanahan |
| author_sort | Catherine M. Shanahan |
| collection | DOAJ |
| description | Vascular stiffening and calcification are hallmarks of ageing and these pathologies are accelerated in patients with diabetes and renal failure. Emerging evidence has defined a role for nuclear lamina defects and the DNA damage response in driving vascular calcification. The mechanisms responsible are linked to the onset of cellular senescence and the activation of the proinflammatory senescence associated secretory phenotype (SASP) in vascular smooth muscle cells (VSMCs). In response to the SASP VSMCs can undergo phenotypic modulation and upregulate expression of proteins normally confined to cells of the osteo/chondrogenic lineage. Understanding the signaling pathways that drive this response is essential for defining novel therapeutic pathways to tackle age-associated vascular pathologies. We have been investigating the role of a number of signaling pathways involved in the DNA damage response as key drivers of calcification and VSMC osteo/chondrogenic differentiation including both the ataxia telangiectasia mutated (ATM) and poly(ADP) ribose (PARP) pathways. In addition it is clear that epigenetic changes, induced by nuclear lamina defects, precede the onset of calcification in both the aged vasculature and in patients with renal failure. |
| first_indexed | 2024-12-12T10:27:22Z |
| format | Article |
| id | doaj.art-ea74b92073b443519e236b87f9e1dfcc |
| institution | Directory Open Access Journal |
| issn | 1876-4401 |
| language | English |
| last_indexed | 2024-12-12T10:27:22Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Artery Research |
| spelling | doaj.art-ea74b92073b443519e236b87f9e1dfcc2022-12-22T00:27:26ZengBMCArtery Research1876-44012018-12-012410.1016/j.artres.2018.10.011MOLECULAR AND CELLULAR CHANGES IN ARTERIAL FUNCTION OVER THE LIFE COURSE – FROM ACCELERATED AGEING TO CALCIFICATIONCatherine M. ShanahanVascular stiffening and calcification are hallmarks of ageing and these pathologies are accelerated in patients with diabetes and renal failure. Emerging evidence has defined a role for nuclear lamina defects and the DNA damage response in driving vascular calcification. The mechanisms responsible are linked to the onset of cellular senescence and the activation of the proinflammatory senescence associated secretory phenotype (SASP) in vascular smooth muscle cells (VSMCs). In response to the SASP VSMCs can undergo phenotypic modulation and upregulate expression of proteins normally confined to cells of the osteo/chondrogenic lineage. Understanding the signaling pathways that drive this response is essential for defining novel therapeutic pathways to tackle age-associated vascular pathologies. We have been investigating the role of a number of signaling pathways involved in the DNA damage response as key drivers of calcification and VSMC osteo/chondrogenic differentiation including both the ataxia telangiectasia mutated (ATM) and poly(ADP) ribose (PARP) pathways. In addition it is clear that epigenetic changes, induced by nuclear lamina defects, precede the onset of calcification in both the aged vasculature and in patients with renal failure.https://www.atlantis-press.com/article/125929980/view |
| spellingShingle | Catherine M. Shanahan MOLECULAR AND CELLULAR CHANGES IN ARTERIAL FUNCTION OVER THE LIFE COURSE – FROM ACCELERATED AGEING TO CALCIFICATION Artery Research |
| title | MOLECULAR AND CELLULAR CHANGES IN ARTERIAL FUNCTION OVER THE LIFE COURSE – FROM ACCELERATED AGEING TO CALCIFICATION |
| title_full | MOLECULAR AND CELLULAR CHANGES IN ARTERIAL FUNCTION OVER THE LIFE COURSE – FROM ACCELERATED AGEING TO CALCIFICATION |
| title_fullStr | MOLECULAR AND CELLULAR CHANGES IN ARTERIAL FUNCTION OVER THE LIFE COURSE – FROM ACCELERATED AGEING TO CALCIFICATION |
| title_full_unstemmed | MOLECULAR AND CELLULAR CHANGES IN ARTERIAL FUNCTION OVER THE LIFE COURSE – FROM ACCELERATED AGEING TO CALCIFICATION |
| title_short | MOLECULAR AND CELLULAR CHANGES IN ARTERIAL FUNCTION OVER THE LIFE COURSE – FROM ACCELERATED AGEING TO CALCIFICATION |
| title_sort | molecular and cellular changes in arterial function over the life course from accelerated ageing to calcification |
| url | https://www.atlantis-press.com/article/125929980/view |
| work_keys_str_mv | AT catherinemshanahan molecularandcellularchangesinarterialfunctionoverthelifecoursefromacceleratedageingtocalcification |