Endothelial activation and damage as a common pathological substrate in different pathologies and cell therapy complications

Front Med (Lausanne). 2023 Nov 14:10:1285898. doi: 10.3389/fmed.2023.1285898. eCollection 2023.

Abstract

The endothelium is a biologically active interface with multiple functions, some of them common throughout the vascular tree, and others that depend on its anatomical location. Endothelial cells are continually exposed to cellular and humoral factors, and to all those elements (biological, chemical, or hemodynamic) that circulate in blood at a certain time. It can adapt to different stimuli but this capability may be lost if the stimuli are strong enough and/or persistent in time. If the endothelium loses its adaptability it may become dysfunctional, becoming a potential real danger to the host. Endothelial dysfunction is present in multiple clinical conditions, such as chronic kidney disease, obesity, major depression, pregnancy-related complications, septic syndromes, COVID-19, and thrombotic microangiopathies, among other pathologies, but also in association with cell therapies, such as hematopoietic stem cell transplantation and treatment with chimeric antigen receptor T cells. In these diverse conditions, evidence suggests that the presence and severity of endothelial dysfunction correlate with the severity of the associated disease. More importantly, endothelial dysfunction has a strong diagnostic and prognostic value for the development of critical complications that, although may differ according to the underlying disease, have a vascular background in common. Our multidisciplinary team of women has devoted many years to exploring the role of the endothelium in association with the mentioned diseases and conditions. Our research group has characterized some of the mechanisms and also proposed biomarkers of endothelial damage. A better knowledge would provide therapeutic strategies either to prevent or to treat endothelial dysfunction.

Keywords: COVID-19; cardiovascular disease; chronic kidney disease; endothelial damage; hematopoietic stem cell transplantation; major depression; obesity; sepsis.

Publication types

  • Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Work partially supported by Fundació Marató de TV3 (202026-10), Instituto de Salud Carlos III (PI14/00226, INT21/00027, PI17/00675, PI18/00073, PI19/00888, PI20/00246, PI22/00684, and PI22/00240) integrados en el Plan Nacional de I+D+I y cofinanciados por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” (Spain), Departament de Recerca i Universitats de la Generalitat de Catalunya (2017-SGR-1531 and 2021-SGR-01118), Contrato Clínico de investigación “Emili Letang-Josep Font,” Centro de Investigación Biomédica en Red de Enfermedades Raras (ERPR04G719/2016) (Spain), Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK), and Fundación Mutua Madrileña (AP180722022). LY had received support from Juan de la Cierva grant FJC2021-048123-I, funded by MCIN/AEI/10.13039/501100011033 and by the European Union NextGenerationEU/PRTR. FC had received support from Fundación para la Investigación Jesus Serra.