ArticleThe Journal of clinical investigation2019
Endothelial progerin expression causes cardiovascular pathology through an impaired mechanoresponse.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 114 citations in OpenAlex.
- Nuclear SUN2 coordinates endothelial cell-matrix interactions to regulate blood vessel homeostasis and barrier function.Angiogenesis · 2026Article
- Human trilayer engineered blood vessel reveals influence of fibroblasts on disease progression in model of Hutchinson-Gilford progeria.Science advances · 2026Article
- Vascular aging as a driver of organ dysfunction and systemic aging.Nature cardiovascular research · 2026Review
- Endothelial Nucleoporin93 (Nup93) Maintains Vascular Homeostasis via Sun1-Dependent Regulation of RhoA/ROCK Activity.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Single-cell analysis of the progeria arterial wall reveals progerin-induced progressive, cell type-specific dysfunction and somatic mutation accumulation.Genome medicine · 2026Article
- Engineering etiology-aligned in vitro models of human vessels.Microsystems & nanoengineering · 2026Review
- Prevalence and Functional Roles of Intrinsic Disorder in the [F-actin]-monooxygenase MICAL Family Members and their Interactors.Cell biochemistry and biophysics · 2026Article
- Nuclear SUN2 coordinates endothelial cell-matrix interactions to regulate blood vessel homeostasis and barrier function.bioRxiv : the preprint server for biology · 2026Article
- Increased Telomere Mobility in Progeria is Restored by Isoprenylcysteine Carboxyl Methyltransferase Inhibition.bioRxiv : the preprint server for biology · 2026Article
- The unfolded protein response in progeria arteries originates from non-endothelial cell types.Life science alliance · 2026Article
- Evidence for Drop-Like Nuclear Deformation in Sheared Endothelial Monolayers.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Nuclear envelope components in vascular mechanotransduction: emerging roles in vascular health and disease.Nucleus (Austin, Tex.) · 2025Review
- Microhand Platform Equipped with Plate-Shaped End-Effectors Enables Precise Probing of Intracellular Structure Contribution to Whole-Cell Mechanical Properties.Micromachines · 2025Article
- Cardiomyocyte-Restricted Expression of Progerin Confers Cardiac Hypertrophy.Circulation research · 2025Article
- Cellular Models of Aging and Senescence.Cells · 2025Review
- Therapeutic potential of CD73Histology and histopathology · 2025Review
- Review
- Endothelial cell-specific progerin expression does not cause cardiovascular alterations and premature death.Aging cell · 2025Article
- Article
- Mechanisms of aging in the cardiovascular system: challenges and opportunities.Frontiers in immunology · 2025Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder characterized by accelerated cardiovascular disease with extensive fibrosis. It is caused by a mutation in LMNA leading to expression of truncated prelamin A (progerin) in the nucleus. To investigate the contribution of the endothelium to cardiovascular HGPS pathology, we generated an endothelium-specific HGPS mouse model with selective endothelial progerin expression. Transgenic mice develop interstitial myocardial and perivascular fibrosis and left ventricular hypertrophy associated with diastolic dysfunction and premature death. Endothelial cells show impaired shear stress response and reduced levels of endothelial nitric oxide synthase (eNOS) and NO. On the molecular level, progerin impairs nucleocytoskeletal coupling in endothelial cells through changes in mechanoresponsive components at the nuclear envelope, increased F-actin/G-actin ratios, and deregulation of mechanoresponsive myocardin-related transcription factor-A (MRTFA). MRTFA binds to the Nos3 promoter and reduces eNOS expression, thereby mediating a profibrotic paracrine response in fibroblasts. MRTFA inhibition rescues eNOS levels and ameliorates the profibrotic effect of endothelial cells in vitro. Although this murine model lacks the key anatomical feature of vascular smooth muscle cell loss seen in HGPS patients, our data show that progerin-induced impairment of mechanosignaling in endothelial cells contributes to excessive fibrosis and cardiovascular disease in HGPS patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.