iPSC-derived endothelial cells reflect accelerated senescence and increased inflammatory response in a CVD-risk stratified manner

Autor:	Mostafa Kiamehr, N.K Kraenkel, E.T Straessler, U.L. Landmesser, Katriina Aalto-Setälä
Rok vydání:	2020
Předmět:	Senescence biology business.industry Inflammation Telomere E-selectin medicine Cancer research biology.protein Increased inflammatory response Tumor necrosis factor alpha medicine.symptom Stem cell Cardiology and Cardiovascular Medicine business Cell aging
Zdroj:	European Heart Journal. 41
ISSN:	1522-9645 0195-668X
Popis:	Background Cardiovascular disease (CVD) remains the leading cause of death worldwide and its multifactorial nature is recognized, with both an individual's genetic background and lifestyle strongly impacting on its course. On a molecular level, accelerated cellular aging and increased inflammation interact to drive the severity of the disease. We have used patient-derived induced pluripotent stem cells (iPSC) to investigate the impact of a patients' genetic background on (epi-)genetically determined functionality, telomere attrition and inflammatory response. Purpose The purpose of this study is to investigate differences on the cellular level between iPSC-derived endothelial cells from risk-stratified CAD patients (both ACS and stable CAD) in both functionality, inflammatory response and ageing rate. Methods iPSCs were generated from participants with similar lifestyle but different disease progression (healthy >65 y/o, stable CAD >65 y/o, ACS Results ACS-iPS-ECs showed a significantly stronger upregulation of E-selectin in response to inflammatory stimulation with TNF-a than healthy-iPS-ECs on mRNA level (ACS: 532.1-fold±48.7 vs. healthy: 322.3-fold±55.7, p=0.02). Similarly, ICAM1 protein upregulation was stronger in ACS-iPS-ECs than in healthy iPSC-ECs as assessed by flow cytometry (ACS: 1.4-fold±0.01 vs. healthy: 1.1-fold±0.0007; p Conclusion The more pronounced upregulation of specific adhesion molecules (E-Selectin, ICAM-1, but not VCAM-1) in response to inflammatory stimulation together with a stronger telomere attrition in ACS-iPS-EC hints at cells entering faster into a senescent state. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Research scholarship from the German Society of Cardiology. Allocated research funds from University hospital.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::cce53d02fe3cf1f73e75e9fedbc4ac8b https://doi.org/10.1093/ehjci/ehaa946.3747 Zobrazit plný text záznamu