The Tgfβ1-Cthrc1 signaling axis plays an important role in the short-term reparative response to heart valve endothelial injury
Autor: | Karthik M. Kodigepalli, Michael R. McDermott, Punashi Dutta, Joy Lincoln, Volkhard Lindner, Stephanie LaHaye, Aaron J. Trask, Emily Nordquist, Carol Mattern |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Aortic valve disease
Aortic valve Male medicine.medical_specialty Aging Endothelium Swine Aortic Diseases Article Extracellular matrix Transforming Growth Factor beta1 Internal medicine medicine Animals Heart valve Cells Cultured Cell Proliferation Extracellular Matrix Proteins business.industry Sequence Analysis RNA Treatment options Extracellular Matrix Up-Regulation Endothelial stem cell Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Cardiology Female Endothelium Vascular Cardiology and Cardiovascular Medicine business Signal Transduction |
Zdroj: | Arterioscler Thromb Vasc Biol |
Popis: | Objective: Aortic valve disease is a common worldwide health burden with limited treatment options. Studies have shown that the valve endothelium is critical for structure-function relationships, and disease is associated with its dysfunction, damage, or injury. Therefore, therapeutic targets to maintain a healthy endothelium or repair damaged endothelial cells could hold promise. In this current study, we utilize a surgical mouse model of heart valve endothelial cell injury to study the short-term response at molecular and cellular levels. The goal is to determine if the native heart valve exhibits a reparative response to injury and identify the mechanisms underlying this process. Approach and Results: Mild aortic valve endothelial injury and abrogated function was evoked by inserting a guidewire down the carotid artery of young (3 months) and aging (16–18 months) wild-type mice. Short-term cellular responses were examined at 6 hours, 48 hours, and 4 weeks following injury, whereas molecular profiles were determined after 48 hours by RNA-sequencing. Within 48 hours following endothelial injury, young wild-type mice restore endothelial barrier function in association with increased cell proliferation, and upregulation of transforming growth factor beta 1 ( Tgfβ1 ) and the glycoprotein, collagen triple helix repeat containing 1 ( Cthrc1 ). Interestingly, this beneficial response to injury was not observed in aging mice with known underlying endothelial dysfunction. Conclusions: Data from this study suggests that the healthy valve has the capacity to respond to mild endothelial injury, which in short term has beneficial effects on restoring endothelial barrier function through acute activation of the Tgfβ1-Cthrc1 signaling axis and cell proliferation. |
Databáze: | OpenAIRE |
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