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Abstract
Valve endothelial cells (VECs) and the underlying layer of valve interstitial cells (VICs) are critical regulators of the heart valve homeostasis and pathologies such as valve calcification. Valvular endothelial cells sense cues from their environment and send signals to interstitial cells to regulate their response. One critical mechanical regulator is blood, which can have a unidirectional or oscillatory flow. These different patterns can have various effects on cells. This study seeks to determine if oscillatory flow characteristics applied to VECs will change the communication factors to valve interstitial cells. A series of oscillatory flow profiles were applied to the VECs. The spent media was collected containing signaling molecules. Valvular interstitial cells were grown in the oscillatory flow conditioned media from VECs to determine the effect of the signals. The calcium deposits left by the interstitial cells were stained and quantified. The most calcification was seen in interstitial cells that received equal amounts of pro-calcific media and the conditioned media from endothelial cells exposed to the highest amount of oscillatory flow. The calcification was substantially lowered in interstitial cells that were grown in media from endothelial cells conditioned in steady flow and intermediate oscillatory flow. We propose that onset of valve calcification may be paracrine regulated (VECs-to-VICs) at high oscillatory flow locations (OSI = 0.50) when regional calcium concentration levels are already augmented. Hence, further discoveries in this paracrine pathway will be important in identifying potential therapeutic targets for valve calcification.