Publications by authors named "M Jesus Andres-Manzano"
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by a mutation in the LMNA gene that provokes the synthesis of progerin, a mutant version of the nuclear protein lamin A that accelerates aging and precipitates death. The most clinically relevant feature of HGPS is the development of cardiac anomalies and severe vascular alterations, including massive loss of vascular smooth muscle cells, increased fibrosis, and generalized atherosclerosis. However, it is unclear if progerin expression in endothelial cells (ECs) causes the cardiovascular manifestations of HGPS.
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- Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder linked to a mutation in the LMNA gene, leading to accelerated aging and early death from cardiovascular issues.
- Research using single-cell RNA sequencing on progerin-expressing mice revealed significant changes in endothelial cells, including alterations in gene expression, increased inflammation, and activation of a pathway (YAP/TAZ) related to mechanosensing.
- Targeting the YAP/TAZ pathway with a drug, verteporfin, reduced inflammation and atherosclerosis in the affected mice, suggesting potential new treatment options for HGPS-related vascular complications.
Article Synopsis
- Atherosclerosis is a major complication in Hutchinson-Gilford progeria syndrome, which is linked to the mutant protein progerin affecting vascular smooth muscle cells (VSMCs).
- Research used various mouse models with progerin expressions specific to different cell types to study how this affects endothelial cells (ECs) during atherosclerosis.
- Findings showed that progerin expression in VSMCs increased EC permeability and leukocyte recruitment to the aorta, highlighting the role of VSMCs in worsening atherosclerosis and suggesting potential therapeutic strategies targeting TGFβ signaling pathways.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by the expression of progerin, a mutant protein that accelerates aging and precipitates death. Given that atherosclerosis complications are the main cause of death in progeria, here, we investigated whether progerin-induced atherosclerosis is prevented in and mice with progerin suppression in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), respectively. mice were undistinguishable from mice with ubiquitous progerin expression, in contrast with the ameliorated progeroid phenotype of mice.
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- Accumulation of lipid-laden macrophages is vital in forming atherosclerotic plaques, and reduced ZEB1 levels in these cells lead to larger plaques and increased cardiovascular risk.
- Male mice lacking ZEB1 in myeloid cells show significant lipid build-up and metabolic issues, indicating that ZEB1 deficiency worsens atherosclerosis.
- Targeted delivery of ZEB1 using nanoparticles can reverse lipid accumulation and reduce plaque formation, suggesting that ZEB1 could be an important therapeutic target for atherosclerosis.