Miner
alocorticoid receptor (MR)
ant
agonists slow down the progression o
f he
art
failure
after myoc
ardi
al in
farction (MI), but the cell-speci
fic role o
f MR in these bene
fits is uncle
ar. In the present study, the role o
f MR expressed in v
ascul
ar smooth muscle cells (VSMC) w
as investig
ated. Two months
after coron
ary
artery lig
ation c
ausing MI, mice with VSMC-speci
fic MR deletion (MI-MRSMKO)
and mice tre
ated with the MR
ant
agonist
finerenone (MI
fine) h
ad improved le
ft ventricul
ar (LV) compli
ance
and el
ast
ance when comp
ared to in
farcted control mice (MI-CTL),
as well
as reduced interstiti
al
fibrosis. Import
antly, the coron
ary reserve
assessed by m
agnetic reson
ance im
aging w
as preserved (di
fference in myoc
ardi
al per
fusion be
fore
and
after induction o
f v
asodil
at
ation, ml/mg/min: MI-CTL: 1.1±0.5, NS; MIMRSMKO: 4.6±1.6, P<0.05; MI-
fine: 3.6±0.7, P<0.01). The endotheli
al
function, tested on isol
ated sept
al coron
ary
arteries by
an
alyzing the
acetylcholineinduced NO-dependent rel
ax
ation, w
as
also improved by MR deletion in VSMC or by
finerenone tre
atment (rel
ax
ation %: MI-CTL: 36±5, MIMRSMKO: 54±3
and MI-
fine: 76±4; P<0.05). Such imp
airment o
f the coron
ary endotheli
al
function upon MI involved
an oxid
ative-stress th
at w
as reduced when MR w
as deleted in VSMC or by
finerenone tre
atment. Moreover, short-term incub
ation o
f coron
ary
arteries isol
ated
from non-in
farcted
anim
als with low dose
angiotensin-II (10-9mol/L) induced oxid
ative-stress
and imp
aired
acetylcholine-induced rel
ax
ation in CTL but neither in MRSMKO nor in mice pre-tre
ated with
finerenone.
ar0010">In conclusion, deletion of MR in VSMC improved LV dysfunction after MI, likely through maintenance of the coronary reserve and improvement of coronary endothelial function. MR blockage by finerenone had similar effects.
ar1005">The author hereby declares no conflict of interest