Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a de novo genetic mutation that leads to the accumulation of a splicing isoform of lamin A termed progerin. Progerin expression alters the organization of the nuclear lamina and chromatin. The life expectancy of HGPS patients is severely reduced due to critical cardiovascular defects. Progerin also accumulates in an age-dependent manner in the vascular cells of adults that do not carry genetic mutations associated with HGPS. The molecular mechanisms that lead to vascular dysfunction in HGPS may therefore also play a role in vascular aging. The vascular phenotypic and molecular changes observed in HGPS are strikingly similar to those seen with age, including increased senescence, altered mechanotransduction and stem cell exhaustion. This article discusses the similarities and differences between age-dependent and HGPS-related vascular aging to highlight the relevance of HGPS as a model for vascular aging. Induced pluripotent stem cells derived from HGPS patients are suggested as an attractive model to study vascular aging in order to develop novel approaches to treat cardiovascular disease.
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Abbreviations
- EC:
-
Endothelial cell
- ECM:
-
Extracellular matrix
- EPC:
-
Endothelial progenitor cell
- ESC:
-
Embryonic stem cell
- HGPS:
-
Hutchinson–Gilford progeria syndrome
- iPSC:
-
Induced pluripotent stem cell
- MSC:
-
Mesenchymal stem cell
- NF:
-
Nuclear factor
- NO:
-
Nitric oxide
- ROS:
-
Reactive oxygen species
- VSMC:
-
Vascular smooth muscle cell
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Acknowledgments
We thank Dr. Gerardo Ferbeyre (Université de Montréal) for reviewing this manuscript, and for his insightful comments and discussion. We also thank Professor Gaétan Laroche (Université Laval and Centre de recherche du CHU de Québec) and William L. Stanford (Ottawa Hospital Research Institute and University of Ottawa) for useful discussions. We thank the Canadian Stem Cell Network (JB, AG and CH), Pfizer Ltd and Pfizer Canada Inc. (See the Potential postdoctoral fellowship awarded to CH), the Canadian Institutes of Health Research (MOP-142285), Saint-Gobain Ceramics & Plastics Inc., the ThéCell Network and the Centre québécois sur les matériaux fonctionnels (CQMF) strategic cluster of the Fonds de recherche du Québec—Nature et technologies for their financial support.
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Brassard, J.A., Fekete, N., Garnier, A. et al. Hutchinson–Gilford progeria syndrome as a model for vascular aging. Biogerontology 17, 129–145 (2016). https://doi.org/10.1007/s10522-015-9602-z
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DOI: https://doi.org/10.1007/s10522-015-9602-z