Ignite Creation Date:
2024-05-06 @ 2:28 PM
Last Modification Date:
2024-10-26 @ 1:31 PM
Study NCT ID:
NCT04322630
Status:
COMPLETED
Last Update Posted:
2021-08-12
First Post:
2020-03-24
Brief Title:
Mer-TK in Human Cardiac Cells
Sponsor:
Ann Robert H Lurie Childrens Hospital of Chicago
Organization:
Ann Robert H Lurie Childrens Hospital of Chicago
Study Overview
Official Title:
Detecting Soluble MER Levels After Myocardial Ischemia and Reperfusion Injury in Pediatric Patients
Status:
COMPLETED
Status Verified Date:
2021-08
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:
The relationship between the immune system and the myocardium after myocardial ischemia is an evolving field of research Crosstalk occurs between macrophages and cardiac myocytes to promote cardio-protection and resolution of inflammation after myocardial ischemia and reperfusion injury MIR injury
Myeloid-epithelial-reproductive tyrosine kinase MerTK a member of the TAM family of tyrosine kinase receptors Tyro-Axl-MerTK is a macrophage receptor that mediates efferocytosis anti-inflammatory signaling and resolution of inflammation After MIR injury intact MerTK is necessary for the phagocytosis of dead cardiac myocytes and to promote anti-inflammatory signaling Proteolytic cleavage of MerTK to its inactive form soluble MER restricts the capacity of macrophages to phagocytize dead cardiac myocytes and impairs MerTK-dependent anti-inflammatory signaling resulting in suppressive effects on cardiac remodeling and function
The Thorp lab at Northwestern University has previously measured soluble MER levels in both adult mice and humans and found that soluble MER concentrations increase after MIR injury In adult MI patients soluble MER was measured post coronary artery reperfusion and was found to be increased average 3200 pgmL compared to 1700 pgmL compared to controls with stable cardiovascular disease Based on murine data the lab further postulated that reperfusion injury may directly interfere with MerTK-dependent cardiac repair as reactive oxygen species formed during reperfusion injury induce proteolytic cleavage of MerTK to soluble MER
Myocardial infarctions are rare events in pediatric patients However pediatric hearts are exposed to periods of hypoperfusion ischemia and inflammation during times of stress such as cardiac bypass and critical illness and it is unknown how soluble MER levels change in response to these events Thus I was interested in investigating how soluble MER levels change after MIR injury induced by cardiac bypass as well as in the utility of soluble MER as a biomarker of cardiac inflammation and injury in pediatric patients
Myeloid-epithelial-reproductive tyrosine kinase MerTK a member of the TAM family of tyrosine kinase receptors Tyro-Axl-MerTK is a macrophage receptor that mediates efferocytosis anti-inflammatory signaling and resolution of inflammation After MIR injury intact MerTK is necessary for the phagocytosis of dead cardiac myocytes and to promote anti-inflammatory signaling Proteolytic cleavage of MerTK to its inactive form soluble MER restricts the capacity of macrophages to phagocytize dead cardiac myocytes and impairs MerTK-dependent anti-inflammatory signaling resulting in suppressive effects on cardiac remodeling and function
The Thorp lab at Northwestern University has previously measured soluble MER levels in both adult mice and humans and found that soluble MER concentrations increase after MIR injury In adult MI patients soluble MER was measured post coronary artery reperfusion and was found to be increased average 3200 pgmL compared to 1700 pgmL compared to controls with stable cardiovascular disease Based on murine data the lab further postulated that reperfusion injury may directly interfere with MerTK-dependent cardiac repair as reactive oxygen species formed during reperfusion injury induce proteolytic cleavage of MerTK to soluble MER
Myocardial infarctions are rare events in pediatric patients However pediatric hearts are exposed to periods of hypoperfusion ischemia and inflammation during times of stress such as cardiac bypass and critical illness and it is unknown how soluble MER levels change in response to these events Thus I was interested in investigating how soluble MER levels change after MIR injury induced by cardiac bypass as well as in the utility of soluble MER as a biomarker of cardiac inflammation and injury in pediatric patients
Detailed Description:
None
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