Secretome of rat smooth muscle cells with stretch

The extracellular matrix (ECM) is fundamental to cellular and tissue structural integrity and provides mechanical cues to initiate diverse biological functions1. The quality and quantity of ECM determines tissue stiffness and controls gene expression, cell fate, and cell cycle progression in various cell types. ECM-cell interactions are mediated by focal adhesions (FAs), the main hub for mechanotransduction, connecting ECM, integrins and cytoskeleton. In the blood vessels, an additional layer of mechanical cues derived from pulsatile blood flow and pressure play a pivotal role in homeostasis and disease development. However, how cells sense and integrate different mechanical cues to maintain the blood vessel wall is largely unknown. Vascular ECM is synthesized by SMCs from mid-gestation to early postnatal period and determines the material and mechanical properties of the blood vessels14. Owing to the long half-life of ECM, blood vessels are generally thought to stand life-long mechanical stress without regeneration, particularly in large arteries. However, it is not completely known whether local micro-remodeling system exists for the maintenance of the vessel wall. To search for a potential remodeling factor(s), we performed cyclic stretch experiments (1 Hz; 20% strain) using rat vascular SMCs for 20 hours (h) with or without Brefeldin A (BFA), a protein transporter inhibitor. Conditioned media (CM) were analyzed using quantitative mass spectrometry.