title: Dynamic Heterogeneity of the Heart Valve Interstitial Cell Population in Mitral Valve Health and Disease.
abstract: The heart valve interstitial cell (VIC) population is dynamic and thought to mediate lay down and maintenance of the tri-laminar extracellular matrix (ECM) structure within the developing and mature valve throughout life. Disturbances in the contribution and distribution of valve ECM components are detrimental to biomechanical function and associated with disease. This pathological process is associated with activation of resident VICs that in the absence of disease reside as quiescent cells. While these paradigms have been long standing, characterization of this abundant and ever-changing valve cell population is incomplete. Here we examine the expression pattern of Smooth muscle α-actin, Periostin, Twist1 and Vimentin in cultured VICs, heart valves from healthy embryonic, postnatal and adult mice, as well as mature valves from human patients and established mouse models of disease. We show that the VIC population is highly heterogeneous and phenotypes are dependent on age, species, location, and disease state. Furthermore, we identify phenotypic diversity across common models of mitral valve disease. These studies significantly contribute to characterizing the VIC population in health and disease and provide insights into the cellular dynamics that maintain valve structure in healthy adults and mediate pathologic remodeling in disease states.
authors.affiliation: Center for Cardiovascular and Pulmonary Research and The Heart Center at Nationwide Children's Hospital Research Institute, 575 Children's Drive, Research Building III, WB4239, Columbus, OH 43215, USA; horne.119@buckeyemail.osu.edu (T.E.H.); matthew.vandekopple@nationwidechildrens.org (M.V.); Sara.Koenig@nationwidechildrens.org (S.N.K.); lindsey.miller@nationwidechildrens.org (L.J.A.); vidu.garg@nationwidechildrens.org (V.G.).
authors.forename: Tori E
authors.initials: TE
authors.lastname: Horne
authors.affiliation: Center for Cardiovascular and Pulmonary Research and The Heart Center at Nationwide Children's Hospital Research Institute, 575 Children's Drive, Research Building III, WB4239, Columbus, OH 43215, USA; horne.119@buckeyemail.osu.edu (T.E.H.); matthew.vandekopple@nationwidechildrens.org (M.V.); Sara.Koenig@nationwidechildrens.org (S.N.K.); lindsey.miller@nationwidechildrens.org (L.J.A.); vidu.garg@nationwidechildrens.org (V.G.).
authors.forename: Matthew
authors.initials: M
authors.lastname: VandeKopple
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA; saulsk@musc.edu (K.S.); norrisra@musc.edu (R.A.N.).
authors.forename: Kimberly
authors.initials: K
authors.lastname: Sauls
authors.affiliation: Center for Cardiovascular and Pulmonary Research and The Heart Center at Nationwide Children's Hospital Research Institute, 575 Children's Drive, Research Building III, WB4239, Columbus, OH 43215, USA; horne.119@buckeyemail.osu.edu (T.E.H.); matthew.vandekopple@nationwidechildrens.org (M.V.); Sara.Koenig@nationwidechildrens.org (S.N.K.); lindsey.miller@nationwidechildrens.org (L.J.A.); vidu.garg@nationwidechildrens.org (V.G.).
authors.forename: Sara N
authors.initials: SN
authors.lastname: Koenig
authors.affiliation: Center for Cardiovascular and Pulmonary Research and The Heart Center at Nationwide Children's Hospital Research Institute, 575 Children's Drive, Research Building III, WB4239, Columbus, OH 43215, USA; horne.119@buckeyemail.osu.edu (T.E.H.); matthew.vandekopple@nationwidechildrens.org (M.V.); Sara.Koenig@nationwidechildrens.org (S.N.K.); lindsey.miller@nationwidechildrens.org (L.J.A.); vidu.garg@nationwidechildrens.org (V.G.).
authors.forename: Lindsey J
authors.initials: LJ
authors.lastname: Anstine
authors.affiliation: Center for Cardiovascular and Pulmonary Research and The Heart Center at Nationwide Children's Hospital Research Institute, 575 Children's Drive, Research Building III, WB4239, Columbus, OH 43215, USA; horne.119@buckeyemail.osu.edu (T.E.H.); matthew.vandekopple@nationwidechildrens.org (M.V.); Sara.Koenig@nationwidechildrens.org (S.N.K.); lindsey.miller@nationwidechildrens.org (L.J.A.); vidu.garg@nationwidechildrens.org (V.G.).|Department of Pediatrics, The Ohio State University, Columbus, OH 43215, USA.
authors.forename: Vidu
authors.initials: V
authors.lastname: Garg
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA; saulsk@musc.edu (K.S.); norrisra@musc.edu (R.A.N.).
authors.forename: Russell A
authors.initials: RA
authors.lastname: Norris
authors.affiliation: Center for Cardiovascular and Pulmonary Research and The Heart Center at Nationwide Children's Hospital Research Institute, 575 Children's Drive, Research Building III, WB4239, Columbus, OH 43215, USA; horne.119@buckeyemail.osu.edu (T.E.H.); matthew.vandekopple@nationwidechildrens.org (M.V.); Sara.Koenig@nationwidechildrens.org (S.N.K.); lindsey.miller@nationwidechildrens.org (L.J.A.); vidu.garg@nationwidechildrens.org (V.G.).|Department of Pediatrics, The Ohio State University, Columbus, OH 43215, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Lincoln
keywords: Periostin; Twist1; Vimentin; activation; mitral valve; smooth muscle α-actin; valve interstitial cell