title: Regurgitation Hemodynamics Alone Cause Mitral Valve Remodeling Characteristic of Clinical Disease States In Vitro.
abstract: Mitral valve regurgitation is a challenging clinical condition that is frequent, highly varied, and poorly understood. While the causes of mitral regurgitation are multifactorial, how the hemodynamics of regurgitation impact valve tissue remodeling is an understudied phenomenon. We employed a pseudo-physiological flow loop capable of long-term organ culture to investigate the early progression of remodeling in living mitral valves placed in conditions resembling mitral valve prolapse (MVP) and functional mitral regurgitation (FMR). Valve geometry was altered to mimic the hemodynamics of controls (no changes from native geometry), MVP (5 mm displacement of papillary muscles towards the annulus), and FMR (5 mm apical, 5 mm lateral papillary muscle displacement, 65% larger annular area). Flow measurements ensured moderate regurgitant fraction for regurgitation groups. After 1-week culture, valve tissues underwent mechanical and compositional analysis. MVP conditioned tissues were less stiff, weaker, and had elevated collagen III and glycosaminoglycans. FMR conditioned tissues were stiffer, more brittle, less extensible, and had more collagen synthesis, remodeling, and crosslinking related enzymes and proteoglycans, including decorin, matrix metalloproteinase-1, and lysyl oxidase. These models replicate clinical findings of MVP (myxomatous remodeling) and FMR (fibrotic remodeling), indicating that valve cells remodel extracellular matrix in response to altered mechanical homeostasis resulting from disease hemodynamics.
authors.affiliation: Department of Bioengineering, Rice University, MS142, 6100 Main St., Houston, TX, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Connell
authors.affiliation: Department of Bioengineering, Rice University, MS142, 6100 Main St., Houston, TX, USA.
authors.forename: Anam F
authors.initials: AF
authors.lastname: Azimuddin
authors.affiliation: Department of Bioengineering, Rice University, MS142, 6100 Main St., Houston, TX, USA.
authors.forename: Seulgi E
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, Rice University, MS142, 6100 Main St., Houston, TX, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ramirez
authors.affiliation: Department of Cardiology, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Jackson
authors.affiliation: Department of Cardiology, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Little
authors.affiliation: Department of Bioengineering, Rice University, MS142, 6100 Main St., Houston, TX, USA. grande@rice.edu.
authors.forename: K Jane
authors.initials: KJ
authors.lastname: Grande-Allen
mesh_terms: D000818:Animals; D018618:Echocardiography, Doppler, Color; D006439:Hemodynamics; D066298:In Vitro Techniques; D008943:Mitral Valve / Q000000981:diagnostic imaging / Q000503:physiopathology; D008944:Mitral Valve Insufficiency / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008945:Mitral Valve Prolapse / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013552:Swine
keywords: Functional mitral regurgitation; Mitral valve prolapse; Mitral valve regurgitation; Myxomatous remodeling; Organ culture