Vitamin A deficiency attenuates cardiac rupture in Stra6-deficient hearts following ischemic injury

Background: Stimulated by retinoic acid gene 6 (STRA6) is a cell surface
receptor that regulates cellular uptake of vitamin A metabolites and cardiac
development. We hypothesized that Stra6 expression attenuates ischemic
injury-induced heart failure following myocardial infarction (MI) by vitamin
A-dependent mechanisms.
Methods: MI was induced in mice with Stra6 germline deletion, vitamin
A deficiency (VitAD) by combined lecithin-retinol acyltransferase (Lrat)
germline deletion and feeding with a vitamin A-deficient diet. Contractile
function was determined by transthoracic echocardiography, cardiac
structure was assessed by histological analysis, and gene profiling was
performed by RNA sequencing.
Results: Stra6 deletion and VitAD did not impact contractile function and
cardiac structure under basal conditions. Stra6 deficiency resulted in
myocardial rupture, with the majority of mice dying by 4 days post-MI, which
additional VitAD attenuated. Interestingly, contractile function, mRNA
expression of heart failure markers, and cardiac structure were not different
between groups 3 days post-MI. Gene profiling 3 days post-MI revealed
decreased Wnt signaling in Stra6-deficient relative to wildtype hearts, which
was reversed by VitAD.
Conclusion: The present study identifies an unexpected role for VitAD, which
preserves Wnt signaling and attenuates cardiac rupture in Stra6-deficient
hearts following ischemic injury.