Publication:
Atherosclerotic Pre-Conditioning Affects the Paracrine Role of Circulating Angiogenic Cells Ex-Vivo

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Date

2020-07-24

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Eslava-Alcon, Sara
Extremera-García, M. Jesús
Sanchez-Gomar, Ismael
Beltrán-Camacho, Lucía
Rosal-Vela, Antonio
Muñoz, Javier
Ibarz, Nuria
Alonso-Piñero, Jose Angel
Rojas-Torres, Marta
Jiménez-Palomares, Margarita

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MDPI
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Abstract

In atherosclerosis, circulating angiogenic cells (CAC), also known as early endothelial progenitor cells (eEPC), are thought to participate mainly in a paracrine fashion by promoting the recruitment of other cell populations such as late EPC, or endothelial colony-forming cells (ECFC), to the injured areas. There, ECFC replace the damaged endothelium, promoting neovascularization. However, despite their regenerative role, the number and function of EPC are severely affected under pathological conditions, being essential to further understand how these cells react to such environments in order to implement their use in regenerative cell therapies. Herein, we evaluated the effect of direct incubation ex vivo of healthy CAC with the secretome of atherosclerotic arteries. By using a quantitative proteomics approach, 194 altered proteins were identified in the secretome of pre-conditioned CAC, many of them related to inhibition of angiogenesis (e.g., endostatin, thrombospondin-1, fibulins) and cell migration. Functional assays corroborated that healthy CAC released factors enhanced ECFC angiogenesis, but, after atherosclerotic pre-conditioning, the secretome of pre-stimulated CAC negatively affected ECFC migration, as well as their ability to form tubules on a basement membrane matrix assay. Overall, we have shown here, for the first time, the effect of atherosclerotic factors over the paracrine role of CAC ex vivo. The increased release of angiogenic inhibitors by CAC in response to atherosclerotic factors induced an angiogenic switch, by blocking ECFC ability to form tubules in response to pre-conditioned CAC. Thus, we confirmed here that the angiogenic role of CAC is highly affected by the atherosclerotic environment.

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Medical Subject Headings::Diseases::Cardiovascular Diseases::Vascular Diseases::Arterial Occlusive Diseases::Arteriosclerosis::Atherosclerosis
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Movement
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation
Medical Subject Headings::Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Cardiovascular Physiological Processes::Neovascularization, Physiologic
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Communication::Paracrine Communication
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal Transduction
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Growth Substances::Angiogenesis Modulating Agents::Angiogenesis Inhibitors
Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Proteomics

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Keywords

Circulating angiogenic cells, Endothelial colony forming cells, Paracrine role, Secretome, Atherosclerotic factors, Angiogenesis, Proteomics, Células, Secretoma, Aterosclerosis, Inhibidores de la angiogénesis, Proteómica, Células progenitoras endoteliales

Citation

Eslava-Alcon S, Extremera-García MJ, Sanchez-Gomar I, Beltrán-Camacho L, Rosal-Vela A, Muñoz J, et al. Atherosclerotic Pre-Conditioning Affects the Paracrine Role of Circulating Angiogenic Cells Ex-Vivo. Int J Mol Sci. 2020 Jul 24;21(15):5256