From:
"Sukie Crandall"
Date: 2007-02-19 21:43:54 UTC
Subject: [ferrethealth] a new approach for heart disease investigated
To: ferrethealth@yahoogroups.com
Now, I DO know that the plural of anecdote is not data, but the longest liv=
ed ferret with
heart disease we ever had (18 months with dilated cardiomyopathy even thoug=
h that
included ventricular bigemini that required Digoxin) was one who lost both =
adrenals early
to carcinoma and went on to have about 5 years more on Fludrocort and Predn=
isolone.=20
I am wondering if the survival of ferrets with cardiomyopathy who have had =
complete
bilateral adrenalectomies (not partials but ones that always require Fludro=
cort and=20
Prednisolone or Percorten and Prednisolone) wind up living longer and bette=
r with heart
disease compared to otherwise comparable ferrets.
BEGIN QUOTE
Public release date: 18-Feb-2007
[ Print Article | E-mail Article | Close Window ]
Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
Targeting the adrenal gland could be key strategy against heart failure, Je=
fferson scientists
show
(PHILADELPHIA) Scientists at the Center for Translational Medicine at Thoma=
s Jefferson
University in Philadelphia have staved off heart failure in animals by usin=
g gene therapy to
shut down the adrenal gland's excessive output of fight or flight hormones =
such as
epinephrine and norepinephrine. By blocking GRK2, an important regulatory e=
nzyme, they
cut the hormone production that forces the heart to pump too hard, leading =
to heart
failure. Such a novel approach =96 targeting the adrenal gland in addition =
to the heart =96
provides a potential new strategy against heart failure, and could lead to =
a new class of
drugs.
The researchers, led by Walter Koch, Ph.D., W.W. Smith Professor of Medicin=
e and director
of the Center for Translational Medicine in the Department of Medicine at J=
efferson Medical
College, report their findings February 18, 2007, in an advance online publ=
ication in the
journal Nature Medicine.
"The emphasis has always been in treating right at the heart," says Stephen=
B. Liggett,
M.D., director of the cardiopulmonary genomics program at the University of=
Maryland
School of Medicine, who has written an accompanying editorial. "Despite our=
best efforts,
about half of all heart failure patients die within five years of diagnosis=
, so clearly
something new is needed. These results add a completely new dimension to th=
e way
physicians might be able to intervene to improve heart failure therapy." Wh=
en an
individual's heart begins to fail, the sympathetic nervous system, attempti=
ng to
compensate for the weakened heart, goes into overdrive, pumping out increas=
ing levels of
stimulants =96 catecholamines such as epinephrine and norepinephrine, makin=
g a bad
situation worse. The typical treatment =96 beta blockers =96 inhibit the be=
ta adrenergic
receptors on the heart, blocking the hormones that force the heart to work =
overtime.
Dr. Koch's group focused instead on the source of catecholamines =96 the ad=
renal gland. It
discovered that in heart failure, the extra hormones "desensitize" the adre=
nal's alpha 2
adrenergic receptors because of a rise in GRK2, or G protein-coupled recept=
or kinase 2,
essentially turning them off. Using gene therapy to block adrenal gland GRK=
2 in animals in
heart failure, the scientists were able to get the alpha 2 receptors workin=
g again and also
found that the beta adrenergic receptors on the heart worked better as well=
.
"We've shown that in the adrenal gland, resetting the alpha adrenergic rece=
ptors by
inhibiting GRK2 causes more normal regulation and the proper feedback contr=
ol, and
catecholamines are lowered," explains Dr. Koch, who also heads the George Z=
allie and
Family Laboratory of Cardiovascular Gene Therapy in the Department of Medic=
ine. "If less
catecholamine is presented to the heart, then the beta receptors restabiliz=
e and that
improves heart function. The heart is allowed to relax and get better."
"This is the first time anyone has identified a molecular mechanism involve=
d in such
sympathetic overdrive in heart failure," adds study first author Anastasios=
Lymperopoulos,
Ph.D., a postdoctoral fellow in the Center for Translational Medicine, and =
means that
adrenal gland GRK2 becomes a new target for heart failure medications.
"GRK2 inhibitors would be a totally new class of drugs if they come on the =
market," Dr.
Koch says, adding that eventually, human gene therapy for heart failure cou=
ld be feasible.
###
Editors: This information is embargoed for release on Sunday, February 18, =
2007 at 1 p.m.
ET
END QUOTE
Yahoo! Groups Links
<*> To visit your group on the web, go to:
http://groups.yahoo.com/group/ferrethealth/
<*> Your email settings:
Individual Email | Traditional
<*> To change settings online go to:
http://groups.yahoo.com/group/ferrethealth/join
(Yahoo! ID required)
<*> To change settings via email:
mailto:ferrethealth-digest@yahoogroups.com
mailto:ferrethealth-fullfeatured@yahoogroups.com
<*> To unsubscribe from this group, send an email to:
ferrethealth-unsubscribe@yahoogroups.com
<*> Your use of Yahoo! Groups is subject to:
http://docs.yahoo.com/info/terms/