FKBPL, a novel angiogenesis-related protein, is downregulated in response to myocardial stress

Alqudah, A; McNally, R; Connell, A; Lyons, T; Grieve, D; Robson, T; McClements, L

FKBPL, a novel angiogenesis-related protein, is downregulated in response to myocardial stress

Alqudah, A McNally, R Connell, A Lyons, T Grieve, D Robson, T McClements, L

Permalink

Publisher:: Springer Science and Business Media LLC
Publication Type:: Conference Proceeding
Citation:: Irish journal of medical science, 2017, 186, (Suppl 9), pp. 343-385
Issue Date:: 2017-09

Closed Access

	Filename	Description	Size
	2017_Article_IrishEndocrineSociety41stAnnua.pdf		1.1 MB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Alqudah, A
dc.contributor.author	McNally, R
dc.contributor.author	Connell, A
dc.contributor.author	Lyons, T
dc.contributor.author	Grieve, D
dc.contributor.author	Robson, T
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014
dc.date	2017-10-13
dc.date.accessioned	2022-03-24T23:50:06Z
dc.date.available	2022-03-24T23:50:06Z
dc.date.issued	2017-09
dc.identifier.citation	Irish journal of medical science, 2017, 186, (Suppl 9), pp. 343-385
dc.identifier.issn	0021-1265
dc.identifier.issn	1863-4362
dc.identifier.uri	http://hdl.handle.net/10453/155531
dc.description.abstract	People with diabetes show five-fold higher incidence of cardiovascular disease, the leading causes of death globally. FKBPL is a novel angiogenesisrelated protein, with a critical role in physiological and pathological angiogenesis. A first-in-class clinical FKBPL peptide mimetic, ALM201, is currently in phase I/II clinical trials for treatment of solid tumours. More recently, in FKBPL knockdown (FKBPL+/-) mice, a pro-angiogenic phenotype was observed, accompanied by vascular dysfunction and a propensity to become overweight and glucose intolerant when fed a high fat diet. We now investigate a specific role for FKBPL in myocardial angiogenesis associated with diabetes. In streptozotocin (STZ) mice, cardiac FKBPL mRNA levels were significantly downregulated at 12 weeks post STZ injection versus vehicle controls (p<0.05, n=5), in association with diastolic dysfunction (e.g. mitral valve E/A ratio). This was in concert with a reduction of FKBPL protein in hearts from STZ-induced vs. control diabetic rats (p<0.01, n=3), also at 12 weeks. Complementary in vitro studies in cultured endothelial cells (HUVEC) demonstrated two-fold reduction in FKBPL protein levels following exposure to hypoxia (1%) for 24 h (p<0.01, n=6), indicating that reduced FKBPL levels observed in vivo may be, at least in part, driven by impaired oxygenation. Indeed, in an experimental mouse model of myocardial infarction (MI), associated with severe cardiac ischaemia/hypoxia and increased angiogenesis, FKBPL mRNA (p<0.05) and protein levels (p<0.01) were downregulated versus sham controls (n≥3). In conclusion, FKBPL may be a key early regulator of cardiac angiogenesis in diabetes, and may thereby hold novel biomarker and therapeutic potential.
dc.format	Print
dc.language	en
dc.publisher	Springer Science and Business Media LLC
dc.relation.ispartof	Irish journal of medical science
dc.relation.ispartof	Irish Endocrine Society 41st Annual Meeting
dc.relation.isbasedon	10.1007/s11845-017-1670-4
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	General & Internal Medicine
dc.title	FKBPL, a novel angiogenesis-related protein, is downregulated in response to myocardial stress
dc.type	Conference Proceeding
utslib.citation.volume	186
utslib.location.activity	Malahide, Dublin
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2022-03-24T23:50:05Z
pubs.finish-date	2017-10-14
pubs.issue	Suppl 9
pubs.publication-status	Published
pubs.start-date	2017-10-13
pubs.volume	186
utslib.citation.issue	Suppl 9

Abstract:

People with diabetes show five-fold higher incidence of cardiovascular disease, the leading causes of death globally. FKBPL is a novel angiogenesisrelated protein, with a critical role in physiological and pathological angiogenesis. A first-in-class clinical FKBPL peptide mimetic, ALM201, is currently in phase I/II clinical trials for treatment of solid tumours. More recently, in FKBPL knockdown (FKBPL+/-) mice, a pro-angiogenic phenotype was observed, accompanied by vascular dysfunction and a propensity to become overweight and glucose intolerant when fed a high fat diet. We now investigate a specific role for FKBPL in myocardial angiogenesis associated with diabetes. In streptozotocin (STZ) mice, cardiac FKBPL mRNA levels were significantly downregulated at 12 weeks post STZ injection versus vehicle controls (p<0.05, n=5), in association with diastolic dysfunction (e.g. mitral valve E/A ratio). This was in concert with a reduction of FKBPL protein in hearts from STZ-induced vs. control diabetic rats (p<0.01, n=3), also at 12 weeks. Complementary in vitro studies in cultured endothelial cells (HUVEC) demonstrated two-fold reduction in FKBPL protein levels following exposure to hypoxia (1%) for 24 h (p<0.01, n=6), indicating that reduced FKBPL levels observed in vivo may be, at least in part, driven by impaired oxygenation. Indeed, in an experimental mouse model of myocardial infarction (MI), associated with severe cardiac ischaemia/hypoxia and increased angiogenesis, FKBPL mRNA (p<0.05) and protein levels (p<0.01) were downregulated versus sham controls (n≥3). In conclusion, FKBPL may be a key early regulator of cardiac angiogenesis in diabetes, and may thereby hold novel biomarker and therapeutic potential.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/155531