Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Prelamin A accumulation accelerates vascular smooth muscle cell (VSMC) senescence, contributing to age-related vascular dysfunction. Targeting prelamin A may offer a novel therapeutic approach for vascular diseases.
Area Of Science
- Cardiovascular Biology
- Cellular Aging
- Molecular Genetics
Background
- Hutchinson-Gilford progeria syndrome involves premature aging due to mutations affecting nuclear lamin A processing and prelamin A accumulation.
- This leads to severe arteriosclerosis, characterized by vascular smooth muscle cell (VSMC) calcification and attrition.
Purpose Of The Study
- To investigate the association between defective lamin A processing and vascular aging in the general population.
- To determine the role of prelamin A in VSMC senescence and vascular dysfunction.
Main Methods
- Examined lamin A expression in normal and aged VSMCs in vitro and in human arteries.
- Assessed prelamin A accumulation, Zmpste24/FACE1 enzyme levels, and VSMC morphology.
- Utilized small interfering RNA (siRNA) to knock down FACE1 and overexpressed prelamin A.
Main Results
- Aged VSMCs accumulated prelamin A, exhibiting nuclear defects reversible with farnesylation inhibitors and statins.
- Prelamin A was prevalent in aged human arteries and atherosclerotic lesions, correlating with VSMC senescence.
- Reduced Zmpste24/FACE1 levels, linked to oxidative stress, exacerbated prelamin A-induced defects; prelamin A overexpression accelerated VSMC senescence.
Conclusions
- Prelamin A is a novel biomarker for VSMC aging and disease, accelerating senescence.
- Prelamin A disrupts mitosis, induces DNA damage, and causes genomic instability in VSMCs.
- Targeting prelamin A offers a potential strategy to mitigate age-related vascular dysfunction.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
This protocol describes the cell culturing of human midbrain dopaminergic neurons, followed by immunological staining and the generation of neuronal phenotypic profiles from acquired microscopic high-content images allowing the identification of phenotypic variations due to genetic or chemical...
In Parkinson's Disease (PD), Substantia Nigra (SNc) dopaminergic neurons degenerate, leading to motor dysfunction. Here we report a protocol for culturing ventral midbrain neurons from a mouse expressing eGFP driven by a Tyrosine Hydroxylase (TH) promoter sequence, harvesting individual fluorescent neurons from the cultures, and measuring their transcriptome using...
The causes of degeneration of midbrain dopaminergic neurons during Parkinson’s disease are not fully understood. Cellular culture systems provide an essential tool for study of the neurophysiological properties of these neurons. Here we present an optimized protocol, which can be utilized for in vitro modeling of...
This protocol describes two different environmental manipulations and a concurrent brain infusion protocol to study environmentally-induced brain changes underlying adaptive behavior and brain repair in adult...
Dopaminergic neurons play a vital regulatory role in the brain. Their loss is associated with Parkinson's disease. In this video, we show how to generate primary cultures of central dopaminergic neurons from embryonic mouse mesencephalon. Such cultures are useful to study the extreme vulnerability of these neurons to various...
Dopamine is distinctly regulated in the midbrain nuclei, which contain the cell bodies and dendrites of the dopamine neurons. Here we describe a dissection and sample-handling approach to maximize results, and thus conclusions and insights, on dopamine regulation in the midbrain nuclei of the substantia nigra (SN) and ventral tegmental area (VTA) in...