March 3, 2026

Roles of Catecholamines and Inflammation in Endothelial Dysfunction: a Study Using Takotsubo Syndrome Patient-specific hiPSC-ECs

Puntos clave

Endothelial dysfunction is associated with elevated catecholamines and inflammatory markers in patients.
Key evidence shows that this dysfunction is notably affected in Takotsubo syndrome cases with inflammation.

PICO estructurado

Do catecholamines and inflammation induce endothelial dysfunction in patient-specific hiPSC-ECs from Takotsubo syndrome patients?

Población

Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) from 1 Takotsubo syndrome (TTS) patient and 3 healthy donors

Intervención

Epinephrine, lipopolysaccharide (LPS), or a combination of both

Comparador

Untreated cells (baseline) and healthy donor hiPSC-ECs

Resultado

Endothelial cell functional responses (cell migration, nitric oxide production, Dil-Ac-LDL uptake, mitochondrial membrane potential, ATP production, tube formation, and wound healing)surrogate

This preclinical study demonstrates that catecholamines and inflammatory signaling drive endothelial dysfunction in Takotsubo syndrome, with patient-specific cells showing intrinsic baseline abnormalities.

Resumen

BACKGROUND: Takotsubo syndrome (TTS), also known as stress-induced cardiomyopathy, is characterized by transient left ventricular dysfunction often triggered by emotional or physical stress. Catecholamines are believed to play a pivotal role in the pathogenesis of TTS, including endothelial dysfunction. This study aimed to elucidate the catecholamine-induced endothelial dysfunction using patient-specific induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) from TTS patients. METHODS: hiPSC-ECs derived from a TTS patient (TTS-hiPSC-ECs) and three healthy donors (HD-hiPSC-ECs) were treated with epinephrine (Epi), Lipopolysaccharide (LPS), or a combination of both, and cell functional responses were evaluated. RESULTS: Epi exposure significantly impaired endothelial cell functions, evidenced by reduced cell migration, nitric oxide (NO) production, Dil-Ac-LDL uptake, mitochondrial membrane potential (MMP), ATP production, and inhibited tube formation and wound healing in both HD-hiPSC-ECs and TTS-hiPSC-ECs. Additionally, catecholamine treatment resulted in increased concentrations of endothelin-1 (ET-1), angiotensin II (Ang II), and reactive oxygen species (ROS) in the supernatants of both cell types. Elevated Mincle expression and pro-inflammatory cytokines, including IL-6 and IL-1β, along with reduced IL-4 protein expression, were observed in both HD-hiPSC-ECs and TTS-hiPSC-ECs. Furthermore, LPS treatment enhanced Mincle, IL-6, and IL-1β protein expression and reduced IL-4 levels in both cell types. The combination of LPS and Epi enhanced not only the level of those inflammatory factors but also the PI3K/NF-κB signaling pathway in both HD-hiPSC-ECs and TTS-hiPSC-ECs. Strikingly, TTS-hiPSC-ECs showed abnormal features even without an Epi challenge. CONCLUSIONS: The study first reveals functional abnormalities of hiPSC-ECs from a TTS patient and underscores the critical involvement of inflammatory signaling in catecholamine-induced endothelial dysfunction in TTS.

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Cite This Study

Yang et al. (Fri,) studied this question.

synapsesocial.com/papers/69a7680dbadf0bb9e87e3696 https://doi.org/https://doi.org/10.1007/s12015-026-11059-y

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