In this study, researchers assessed the cardio problems in astronauts returning from a prolonged spaceflight. These health problems might be driven by complex modulations of gene expression and protein synthesis in endothelial cells (ECs). Studies on the influence of microgravity on phenotype, growth pattern and biological processes of ECs can help to understand these complications.

The impact of microgravity on different cell types is currently a topic of interest. Astronauts suffer from various health problems after long-term space travel. Cardiovascular problems like hypotension and arrhythmias might occur. A recent study showed that a dysfunctional vestibular system induces a blood pressure drop in astronauts returning from a space mission.

Endothelial cells (ECs) play a key role in the pathogenesis of various diseases and are highly sensitive to microgravity. ECs were investigated in space on the International Space Station (ISS) and Earth using techniques to simulate microgravity. A recent study showed that ras homolog gene family member A (RhoA) inactivation supports the actin rearrangement-associated angiogenic responses in human umbilical vein endothelial cells (HUVECs) during simulated microgravity.

Early cytoskeletal changes of microgravity-exposed ECs have previously been described in real and simulated microgravity. In this study, we focused on long-term changes of ECs exposed to an RPM for 35 days and investigated proteins known to be involved in the process of angiogenesis as well as factors secreted into the culture supernatant.

 The relationship of factors driving the 3D growth of ECs in a microgravity-dependent system such as vascular endothelial growth factor (VEGF) and its receptors fetal liver kinase 1 (Flk1 or kinase insert domain receptor (KDR) or VEGFR-2) and Fms-related tyrosine kinase 1 (Flt1 or VEGFR-1),

Cytokines like the interleukins (IL)-6 and IL-8, plasminogen activator inhibitor 1 (PAI-1), monocyte chemoattractant protein 1 (MCP-1 or CCL2), the cell adhesion molecules vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) were investigated.

Also, we measured NGAL by TRIFMA. Recent publications showed that NGAL, a biomarker for kidney disease also has pathophysiological importance in cardiovascular diseases. Furthermore, NGAL had been detected in different cancer types. Its role in the 3D growth of ECs must be studied in more detail in the future.

A long-term exposure to EA. hy926 cells to the RPM changed the growth behavior of the cells. Like observed on primary microvascular endothelial cells, three different phenotypes appeared: adherently growing cells at the bottom of the culture flasks, multicellular spheroids and 3D tubular structures, both in suspension in the culture supernatant.

Consistent with earlier data and observations made during the ESA-SPHEROIDS space mission to the ISS, the MCS developed during the first two weeks. Especially MCP-1 and NGAL are interesting targets for future experiments.