Paradoxical aortic stiffening and subsequent cardiac dysfunction in Hutchinson-Gilford progeria syndrome.

ABSTRACT: Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare disorder with devastating sequelae resulting in early death, presently thought to stem primarily from cardiovascular events. We analyse novel longitudinal cardiovascular data from a mouse model of HGPS (Lmna^G609G/G609G) using allometric scaling, biomechanical phenotyping, and advanced computational modelling and show that late-stage diastolic dysfunction, with preserved systolic function, emerges with an increase in the pulse wave velocity and an associated loss of aortic function, independent of sex. Specifically, there is a dramatic late-stage loss of smooth muscle function and cells and an excessive accumulation of proteoglycans along the aorta, which result in a loss of biomechanical function (contractility

SUBMITTER: Murtada SI 

PROVIDER: S-EPMC7276555 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature