The Role of Purinergic Signaling in Endothelial and Smooth Muscle Cells under Simulated Microgravity

Abstract

Astronauts suffer from cardiovascular deconditioning during space flight where they are exposed to microgravity. Alterations under real and simulated microgravity have been found e.g. in the cytoskeleton and apoptosis in endothelial cells (ECs) and smooth muscle cells (SMCs)1, 2. P2 receptors play an important role in a variety of vascular functions of ECs and SMCs. However, the functional role of purinergic signalling in ECs and SMCs under microgravity is still unclear. In this study primary ECs and SMCs were isolated from bovine aorta and characterized using specific markers. Additionally, EC growth medium collected during culture under normal gravity was used as conditioned medium for SMCs and vice versa to mimic a co-culture model. Here we show for the first time that the P2-receptor expression pattern is altered in ECs and SMCs under simulated microgravity achieved by a clinostat. Interestingly, conditioned medium compensated the alterations in the expression of specific P2-receptors. P2X7 was down-regulated in ECs after 24h clinorotation but recovered to the gene and protein expression level found under normal gravity when cultured in conditioned medium from SMCs. Our results showed an altered P2-receptor expression pattern under simulated microgravity. The paracrine effect between ECs and SMCs seems to be an important regulator of cell behaviour under altered gravity conditions. Several artificial P2-receptor ligands are already utilized as drugs. Thus it might be reasonable to consider them for drug development for astronaut treatment of cardiovascular deconditioning in the future.