Mer-TK in Human Cardiac Cells

NCT04322630 | Completed

• 1 other identifier: 2019-2445
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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 (MI/R 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 MI/R 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 MI/R injury. In adult MI patients, soluble MER was measured post coronary artery reperfusion and was found to be increased (average 3200 pg/mL compared to 1700 pg/mL) 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 MI/R 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.

Conditions

Myocardial Inflammation; Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• Change in Soluble MER Concentration

  5/10/2019-12/31/2020

Secondary Outcomes (1)

• Utility of soluble MER as a biomarker of inflammation and injury

  5/10/2019-12/31/2020

Study Arms (1)

Pediatric Cardiac Bypass Patients

Blood samples obtained from patients ages from birth-19 years-old as well as cyanotic and acyanotic cardiac lesions who underwent cardiac bypass.

Other: Change in Soluble MER Concentration

Interventions

Change in Soluble MER Concentration OTHER

Measuring change in soluble MER Concentration post compared to pre bypass for each patient.

Pediatric Cardiac Bypass Patients

Eligibility Criteria

• Age: Up to 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Pediatric patients with congenital heart disease presenting to Lurie Children's Hospital for corrective or palliative heart surgery and will be undergoing cardiac bypass.

You may qualify if:

• All patient ages from birth-19 years-old as well as cyanotic and acyanotic cardiac lesions will be included

You may not qualify if:

• Patients will be excluded if both pre and post bypass blood samples are not available.

Sponsors & Collaborators

• Ann & Robert H Lurie Children's Hospital of Chicago: lead

Study Sites (1)

Ann & Robert H Lurie Children's Hopsital

Chicago, Illinois, 60611, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Human blood samples obtained intra-operatively during cardiac bypass.

MeSH Terms

Conditions

Myocarditis; Myocardial Infarction

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: March 26, 2020
• Study Start: May 10, 2019
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: August 12, 2021

Record last verified: 2021-08

Locations

US (1)