SFEBES2023 Poster Presentations Neuroendocrinology and Pituitary (74 abstracts)
Hindering the progression of cardiac fibrosis in acromegaly – the role of somatostatin receptor ligands
Kanokporn Sanpawithayakul 1,2 , Anisha Mistry 1 , Ashutosh Rai 1 , Gregory Funge 1,3 , Sonia Sebastian 3 , Antonia Solomou 1,4 , Maria Lillina Vignola 1,4 , Carles Gaston-Massuet 1 , Andrew Tinker 3 , Federica Begalli 1 & Márta Korbonits 1
1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand. 3Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. 4Department of Medical and Molecular Genetics, Guy’s Hospital, KCL, London, United Kingdom
Introduction: Acromegaly links to cardiomyopathy and potential cardiac failure, if untreated. Mechanisms involved in acromegalic cardiomyopathy are incompletely understood. We investigated the effects of growth hormone (GH) excess and somatostatin receptor ligands (SRLs) on cardiac fibrosis using an acromegalic mouse model with pituitary-specific deletion of the Aip gene coding aryl hydrocarbon receptor interacting protein (AipFlox/Flox;Hesx1Cre/+), causing early-onset acromegaly characterised by GH-secreting tumours, greater body weight, and elevated IGF-1 levels.
Materials and Methods: Heart samples were collected from pituitary-specific Aip knockout (KO, AipFlox/Flox;Hesx1Cre/+) and littermate control (WT) mice at 3, 6, 9, 12, and 15 months (n=54). Another group of KO animals received monthly subcutaneous injections from age 3-month of either long-acting octreotide (30μg/g body weight; n=6), pasireotide (60μg/g; n=7), or vehicle control (n=6). Cardiac interstitial and perivascular fibrosis were assessed by picrosirius red staining and QuPath scoring.
Results: Heart fibrosis, both interstitial and perivascular, was significantly higher in KO mice compared to age-matched control. The extent of interstitial cardiac fibrosis in KO mice was gradually increasing and reached statistical significance from as early as 3-months-old (mean±SEM: KO 1.73±0.46% vs. WT 0.19±0.09%, P<0.01). Perivascular fibrosis in KO mice started increasing at 3-months-old and reached significance at 6-months-old (KO 4.28±0.34% vs. WT 1.07±0.09% (P=0.01). These significant differences persisted at 15-months-old in both groups. In SRL-treated KO animals, octreotide significantly reduced interstitial fibrosis compared to the control group (1.73±0.16% vs. 0.99±0.25, P=0.04), and revealed a trend in reducing perivascular fibrosis (P=0.08), while pasireotide did not reduce fibrosis.
Conclusion: Acromegalic mice showed progressive intracardiac fibrosis over time. Direct effect of SRLs on cardiac tissue, probably through somatostatin receptor 2, as well as hormonal effects on GH/IGF-1 play a role in the treatment effects on the heart. Octreotide represents a promising approach in delaying interstitial and perivascular fibrosis.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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