Progerinin, an Inhibitor of Progerin, Alleviates Cardiac Abnormalities in a Model Mouse of Hutchinson-Gilford Progeria Syndrome.

ABSTRACT

Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare human premature aging disorder that precipitates death because of cardiac disease. Almost all cases of HGPS are caused by aberrant splicing of the LMNA gene that results in the production of a mutant Lamin A protein termed progerin. In our previous study, treatment with Progerinin has been shown to reduce progerin expression and improve aging phenotypes in vitro and in vivo HGPS models. In this record, cardiac parameters (stroke volume (SV), ejection fraction (EF), fractional shortening (FS), etc.) were acquired in LmnaWT/WT and LmnaG609G/WT mice fed with either a vehicle diet or a Progerinin diet by echocardiography (from 38 weeks to 50 weeks at various ages), and then the cardiac function was analyzed. We also acquired the tissue samples and blood serum of LmnaWT/WT and LmnaG609G/WT mice for pathological analysis at the end of echocardiography. From these data, we suggest that the administration of Progerinin in the HGPS model mouse can restore cardiac function and correct arterial abnormalities. These observations provide encouraging evidence for the efficacy of Progerinin for cardiac dysfunction in HGPS.