Abstract
Hutchinson-Gilford progeria syndrome (HGPS) and other progeroid (premature aging) syndromes are attributable to lamin A processing defects; these result in aberrant nuclear architectures that impact normal transcription and translation, resulting in a premature aging phenotype at the cellular, tissue, and organismal levels. Patients with HGPS are characterized by severe accelerated cardiovascular disease, including valvular calcification and vessel wall stiffening and calcification as well as atherosclerosis, typically culminating in premature death due to myocardial infarction or stroke. Understanding the mechanisms of the early and aggressive vascular and valvular calcification (and vascular atherosclerosis) in the progeroid syndromes may cast important light on the pathways (and therapies) relevant for physiologic aging and senescence.
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Abbreviations
- EC:
-
Endothelial cells
- eNOS:
-
Endothelial nitric oxide synthase
- eNTPD1:
-
Ectonucleoside triphosphate diphosphohydrolase-1
- FACE-1:
-
Farnesylated protein converting enzyme-1
- HGPS:
-
Hutchinson-Gilford progeria syndrome
- KLF2:
-
Krüppel-like factor 2
- PPi:
-
Inorganic pyrophosphate
- ROS:
-
Reactive oxygen species
- TNAP:
-
Tissue non-specific alkaline phosphatase
- VSMC:
-
Vascular smooth muscle cells
- ZMPSTE24:
-
Zinc metalloproteinase STE24
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Acknowledgments
The author wishes to recognize with appreciation the outstanding and innovative research and the comprehensive HGPS reviews developed by Dr. Vicente Andrés and colleagues at Centro Nacional de Investigaciones Cardiovasculares Carlos III in Madrid, Spain. In addition, Dr. Leslie B. Gordon (Hasbro Children’s Hospital and the Alpert Medical School of Brown University in Providence, RI, and Medical Director of the Progeria Research Foundation) has been a tireless and eloquent international leader and advocate in the pursuit of the understanding and treatment of HGPS; without Dr. Gordon and her colleagues at the PRF, we would know only a fraction of what is understood about the disease.
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Mitchell, R.N. (2020). Cardiovascular Calcification in Hutchinson-Gilford Progeria and Correlation with Age-Related Degenerative Calcification. In: Aikawa, E., Hutcheson, J. (eds) Cardiovascular Calcification and Bone Mineralization. Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-030-46725-8_11
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DOI: https://doi.org/10.1007/978-3-030-46725-8_11
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