Cardiac troponin I Pro82Ser variant induces diastolic dysfunction, blunts β-adrenergic response, and impairs myofilament cooperativity.

ABSTRACT: Troponin I (TnI) variant Pro82Ser (cTnIP82S) was initially considered a disease-causing mutation; however, later studies suggested the contrary. We tested the hypothesis of whether a causal link exists between cTnIP82S and cardiac structural and functional remodeling, such as during aging or chronic pressure overload. A cardiac-specific transgenic (Tg) mouse model of cTnIP82S was created to test this hypothesis. During aging, Tg cTnIP82S displayed diastolic dysfunction, characterized by longer isovolumetric relaxation time, and impaired ejection and relaxation time. In young, Tg mice in vivo pressure-volume loops and intact trabecular preparations revealed normal cardiac contractility at baseline. However, upon β-adrenergic stimulation, a blunted contractile reserve and no hastening in lef

SUBMITTER: Ramirez-Correa GA 

PROVIDER: S-EPMC4297775 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature