BACKGROUND: Increased @entity750 ( @entity750 [5HT]) receptor (5HTR) signaling has been associated with @entity299 . Prior cell culture studies of 5HTR signaling in heart valve interstitial cells have provided mechanistic insights concerning only static conditions. We investigated the hypothesis that aortic valve biomechanics participate in the regulation of both 5HTR expression and interrelated extracellular matrix remodeling events. METHODS: The effects of cyclic stretch on aortic valve 5HTR, expression, signaling, and extracellular matrix remodeling were investigated using a tensile stretch bioreactor in studies which also compared the effects of adding 5HT and (or) the @entity16068 inhibitor, @entity905 . RESULTS: Cyclic stretch alone increased both proliferation and collagen in porcine aortic valve cusp samples. However, with cyclic stretch, unlike static conditions, 5HT plus @entity905 caused the greatest increase in proliferation (p<0.0001), and also caused significant increases in collagen (p<0.0001) and glycosaminoglycans (p<0.0001). The DNA microarray data demonstrated upregulation of 5HTR2A and 5 @entity44358 (>4.5-fold) for cyclic stretch versus static (p<0.001), while expression of the @entity16068 was not changed significantly. Extracellular matrix genes (eg, collagen types I, II, III, and proteoglycans) were also upregulated by cyclic stretch. CONCLUSIONS: Porcine aortic valve cusp samples subjected to cyclic stretch upregulate 5HTR2A and 2B, and also initiate remodeling activity characterized by increased proliferation and collagen production. Importantly, enhanced 5HTR responsiveness due to increased 5HTR2A and 2B expression results in a significantly greater response in remodeling endpoints (proliferation, collagen, and GAG production) to 5HT in the presence of @entity16068 blockade.

Aortic valve cyclic stretch causes increased remodeling activity and enhanced XXXX receptor responsiveness.

@entity905 :: ('MESH:D005473', 'Chemical') :: ['fluoxetine'] @entity16068 :: ('6532', 'Gene') :: ['5HT-transporter', '5HT transporter'] @entity44358 :: ('3357', 'Gene') :: ['HTR2B'] @entity750 :: ('MESH:D012701', 'Chemical') :: ['5-hydroxytryptamine', 'serotonin'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac valvulopathy']
@entity750 :: (MESH:D012701,Chemical) :: ['serotonin']
