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The Effect of Cyclic Strain on Human Fibroblasts With Lamin A/C Mutations and Its Relation to Heart Disease
Author(s) -
Ryan Tran,
Mark E. Siemens,
Christopher Nguyen,
Alexander Ochs,
Michael V. Zaragoza,
Anna Grosberg
Publication year - 2020
Publication title -
journal of biomechanical engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.546
H-Index - 126
eISSN - 1528-8951
pISSN - 0148-0731
DOI - 10.1115/1.4044091
Subject(s) - lmna , lamin , progeria , mutation , gene mutation , biology , nuclear lamina , extracellular matrix , microbiology and biotechnology , heart disease , genetics , cancer research , medicine , pathology , gene , nuclear protein , transcription factor
Although mutations in the Lamin A/C gene (LMNA) cause a variety of devastating diseases, the pathological mechanism is often unknown. Lamin A/C proteins play a crucial role in forming a meshwork under the nuclear membrane, providing the nucleus with mechanical integrity and interacting with other proteins for gene regulation. Most LMNA mutations result in heart diseases, including some types that primarily have heart disease as the main pathology. In this study, we used cells from patients with different LMNA mutations that primarily lead to heart disease. Indeed, it is a mystery why a mutation to the protein in every nucleus of the body manifests as a disease of primarily the heart in these patients. Here, we aimed to investigate if strains mimicking those within the myocardial environment are sufficient to cause differences in cells with and without the LMNA mutation. To test this, a stretcher device was used to induce cyclic strain upon cells, and viability/proliferation, cytoskeleton and extracellular matrix organization, and nuclear morphology were quantified. The properties of cells with Hutchinson-Gilford progeria syndrome (HGPS) were found to be significantly different from all other cell lines and were mostly in line with previous findings. However, the properties of cells from patients who primarily had heart diseases were not drastically different when compared to individuals without the LMNA mutation. Our results indicated that cyclic strain alone was insufficient to cause any significant differences that could explain the mechanisms that lead to heart diseases in these patients with LMNA mutations.

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