Paracrine Shear-Stress-Dependent Signaling from Endothelial Cells Affects Downstream Endothelial Function and Inflammation

• Published in: International journal of molecular sciences 2021-12, Vol.22 (24), p.13300
• Main Authors: Bertani, Fabio, Di Francesco, Dalila, Corrado, Maria Dolores, Talmon, Maria, Fresu, Luigia Grazia, Boccafoschi, Francesca
• Format: Article
• Language: English
• Subjects: Adhesion; Angiogenesis; Arteriosclerosis; Atherosclerosis; Cardiovascular disease; Cardiovascular diseases; Cell adhesion molecules; Cell culture; Coronary artery disease; E-selectin; Endothelial cells; endothelial dysfunction; Endothelium; Enzymes; Experiments; Heart diseases; Heterogeneity; Human Umbilical Vein Endothelial Cells - metabolism; Human Umbilical Vein Endothelial Cells - pathology; Humans; Inflammation; Inflammation - metabolism; Inflammation - pathology; inflammatory response in endothelial cells; Intercellular adhesion molecule 1; Ischemia; Localization; Mechanical stimuli; Mechanotransduction; Microfluidics; microvascular dysfunction; Microvasculature; Morphology; Nitric oxide; Nitric-oxide synthase; Paracrine Communication; Paracrine signalling; Peripheral blood mononuclear cells; Physiology; Protein expression; Proteins; Shear forces; Shear Strength; Shear stress; Stress, Mechanical; Tumor necrosis factor-α; Viscosity; Wall shear stresses
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222413300

Cardiovascular diseases (CVDs), mainly ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and major contributors to disability worldwide. Despite their heterogeneity, almost all CVDs share a common feature: the endothelial dysfunction. This is defined as a loss of functionality in terms of anti-inflammatory, anti-thrombotic and vasodilatory abilities of endothelial cells (ECs). Endothelial function is greatly ensured by the mechanotransduction of shear forces, namely, endothelial wall shear stress (WSS). Low WSS is associated with endothelial dysfunction, representing the primary cause of atherosclerotic plaque formation and an important factor in plaque progression and remodeling. In this work, the role of factors released by ECs subjected to different magnitudes of shear stress driving the functionality of downstream endothelium has been evaluated. By means of a microfluidic system, HUVEC monolayers have been subjected to shear stress and the conditioned media collected to be used for the subsequent static culture. The results demonstrate that conditioned media retrieved from low shear stress experimental conditions (LSS-CM) induce the downregulation of endothelial nitric oxide synthase (eNOS) expression while upregulating peripheral blood mononuclear cell (PBMC) adhesion by means of higher levels of adhesion molecules such as E-selectin and ICAM-1. Moreover, LSS-CM demonstrated a significant angiogenic ability comparable to the inflammatory control media (TNFα-CM); thus, it is likely related to tissue suffering. We can therefore suggest that ECs stimulated at low shear stress (LSS) magnitudes are possibly involved in the paracrine induction of peripheral endothelial dysfunction, opening interesting insights into the pathogenetic mechanisms of coronary microvascular dysfunction.