Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.576724
Title: The characterisation of growth hormone-related cardiac disease with magnetic resonance imaging & The effects of growth hormone dysregulation on adenosine monophosphate-activated protein kinase in cardiac tissue
Author: Thomas, Julia Dominique Janine
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2012
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.576724  DOI: Not available
Keywords: Medicine
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