Ignite Creation Date:
2024-05-06 @ 7:27 PM
Last Modification Date:
2024-10-26 @ 3:07 PM
Study NCT ID:
NCT06015776
Status:
RECRUITING
Last Update Posted:
2023-08-29
First Post:
2023-08-23
Brief Title:
Purinergic Signaling and the Postmenopausal Heart
Sponsor:
Beth Israel Deaconess Medical Center
Organization:
Beth Israel Deaconess Medical Center
Study Overview
Official Title:
PGC-1 Purines and the Postmenopausal Heart
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
There is an increased risk of diastolic heart failure in post menopausal women Estrogen plays a positive role in regulating molecular pathways in heart remodeling Such pathways may work through purinergic signaling and its downstream effects on the hearts mitochondrial metabolism and angiogenic response to stress Loss of estrogen functionality in post menopausal women may account for the increased risk of diastolic heart failure The investigators will explore said pathways using cardiac tissue obtained from patients undergoing cardiac surgery
Detailed Description:
Cardiovascular disease CVD is the leading cause of death of women in the United States accounting for around 1 of every 3 deaths Estrogen deficiency as seen in aging women or after oophorectomy has been linked to loss of cardiovascular protection typically seen during reproductive life Up to half of women evaluated for myocardial ischemia have normal appearing coronary arteries These women can develop heart failure with a preserved ejection fraction termed HFpEF for which the etiology is unclear Hormonal replacement therapy HRT after menopause remains controversial but current evidence cannot support this for either primary or secondary prevention of CVD There are clearly modulatory influences on estrogenic signaling that could well influence cardiovascular health in later life Previous studies have demonstrated that estrogen improves energy production within the heart by increasing 5 adenosine monophosphate-activated protein AMPK and mitochondrial biogenesis via upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha PGC-1α a master switch of mitochondrial function linked to vascular integrity and angiogenesis Estrogen has been also found to modulate purinergic signaling by boosting expression of adenosine receptors and of CD39 the dominant endothelial ecto-ADPase that generates adenosine There are also close relationships between purinergic signaling and dipeptidyl peptidase-4 DPP-4 otherwise known as adenosine deaminase complexing protein 2 or CD26 possibly mediated by adenosine deaminase bioactivity Decreased PGC-1α and aberrant purinergic signaling in metabolic syndrome may lead to impaired mitochondrial function provoking diastolic dysfunction and also result in impaired angiogenesis The investigators hypothesize there are central roles of PGC-1α purines and DPP-4 linked neuropeptide pathways in the control of angiogenesis and mitochondrial activity These become increasingly disordered in setting of estrogen loss provoking development of metabolic syndrome thereby exacerbating HFpEF and microvascular disease Specific Aim 1 To determine how ischemia and cardiometabolic dysfunction in womens heart disease are exacerbated by the loss of puringeric pathways from estrogen deficiency The investigators expect to determine that diastolic dysfunction is a functional consequence of this microvascular loss and cardiometabolic dessynchrony Specific Aim 2 To evaluate the role of adenosingergic receptor activation and DPPIV inhibition on angiogenesis in a ovariectomized swine model of chronic myocardial ischemia and metabolic syndrome Here the investigators will explore relationships between the regulated and linkages in the exocytosis of nucleotides and neuropeptides formation of nucleosides adenosine and alterations in angiogenic activity secondary to these Summary The investigators will study fundamental mechanisms in heart disease underpinning biological differences in women The investigators will also offer new therapeutic strategies that target cardiac metabolism
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None