| dc.description.abstract | Chronic growth hormone (GH) excess, acromegaly, causes a specific cardiomyopathy, which
remains poorly understood. The pattern of hypertrophy is distinct from other forms of cardiac
disease and begins to appear before hypertension or diabetes. GH deficiency (GHD) also
causes cardiovascular problems, with reduced ability to mount a cardiovascular response to
exercise. Acromegaly and GHD patients have increased cardiac mortality.
Cardiac magnetic resonance imaging (CMR) is the gold standard for assessment of cardiac
mass and provides data on cardiac function, fibrosis, valve function and ischaemia. This
study used CMR to assess 23 patients with acromegaly or GHD, before and after treatment
of their GH disorder, and 23 healthy controls. Patients with acromegaly demonstrated
increased left ventricular mass index (LVMi), end diastolic volume index, stroke volume index
and cardiac index, which persisted at one year, despite treatment of underlying disease.
Patients with GHD demonstrated LVMi at the bottom (males) or beneath (females) published
normal references ranges, which increased with one year of GH replacement.
The mechanisms by which GH influences cardiac tissue are poorly understood. Adenosine
monophosphate-activated protein kinase (AMPK) is an energy-regulator enzyme, which
interacts with several metabolic hormones. Mutations in AMPK cause arrhythmias and
cardiac hypertrophy. AMPK activation may be a mechanism by which GH causes some of its
cardiac effects.
This study used primary cardiomyocytes and mouse and rat models of GH excess and
deficiency to study the effects of GH on cardiac AMPK. Acute GH treatment increased
AMPK activity in both in vivo and in vitro studies; acute IGF-I treatment had the opposite
effect. In 2 and 8 month old bovine GH-overexpressing (bGH) and GH receptor knock out
(GHRKO) mice, functional AMPK assay did not demonstrate any difference in cardiac AMPK
activity between transgenics and controls. However, Western blotting for Threonine-172
phospho (p)AMPK levels, a marker of AMPK activity, demonstrated increased cardiac
pAMPK in 2 month old bGH mice and a reduction in cardiac pAMPK levels in 8 month old
animals. A trend towards the same findings was seen in GHRKO mice. This indicates that
both GH and IGF-I interact with myocardial AMPK, apparently via different mechanisms. | en_US |
