Coronary Imaging
Nour Shams, BSc
Postbaccalaureate Research Fellow
National Institute of Diabetes and Digestive and Kidney Diseases, Maryland, United States
Nour Shams, BSc
Postbaccalaureate Research Fellow
National Institute of Diabetes and Digestive and Kidney Diseases, Maryland, United States
Ahmed M. Gharib, MD
Senior Investigator
National Institute of Diabetes and Digestive and Kidney Diseases, Maryland, United States
Jehad Edwan, PhD
Senior Research Fellow
National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Maryland, United States
Aruba Chowdhury, BSc
Postbaccalaureate Research Fellow
National Institute of Diabetes and Digestive and Kidney Diseases, Maryland, United States
Raj Jatin Matta, PhD
Researcher/ Associate Investigator
National Institute of Diabetes and Digestive and Kidney Diseases, Maryland, United States
Katrina Dietsche, BSc
Postbaccalaureate Research Fellow
National Institute of Diabetes and Digestive and Kidney Diseases, United States
Sydney Dixon, BSc
Postbaccalaureate Research Fellow
National Institute of Diabetes and Digestive and Kidney Diseases, United States
Michael Stagliano, RN
Family Nurse Practitioner
National Institute of Diabetes and Digestive and Kidney Diseases, United States
Lillian Mabundo, MSc, RN
Research Nurse Specialist
National Institute of Diabetes and Digestive and Kidney Diseases, United States
Colleen Hadigan, MD, MPH
Senior Research Fellow
National Institutes of Health Clinical Center, United States
Stephanie Chung, MD
Senior Research Fellow
National Institute of Diabetes and Digestive and Kidney Diseases, United States
Khaled Z. Abd-Elmoniem, PhD
Staff Scientist
National Institute of Diabetes and Digestive and Kidney Diseases, Maryland, United States
Jenna Feeley, BSc
Fellow
National Institute of Diabetes and Digestive and Kidney Diseases, Maryland, United States
A total of 30 subjects were included and signed informed consent for this prospective study. MRI-integrated isometric handgrip exercise system with continuous feedback and monitoring mechanisms (fmIHE) was used to quantify coronary endothelial function by measuring right coronary cross-sectional area flow-mediated dilatation (CorFMD) and vessel wall thickness (CWT) using 3T MR (Philips,). Images were collected at baseline and during five minutes of continuous fmIHE at a constant 33% of each subject’s maximum grip strength. Adherence to the predetermined gripping strength was accomplished using an MRI-compatible in-house developed handgrip system with audiovisual feedback (Figure 1). Coronary MR angiography (MRA) was obtained for the right coronary artery (RCA) and cross-section area images from the proximal segment. MRA used free-breathing navigator-gated cine spiral MRI with in-plane spatial resolution= 0.73x0.73. CWT was also obtained at the same location using free-breathing time-resolved phase-sensitive dark-blood (TRAPD)3 using inversion time (TI = 200 ms). In a subset of 4 Y-T2D, we isolated, characterized, and incubated plasma-derived exosomes in human coronary artery epithelial cells (HCAECs) vs. control cells. Samples were analyzed by western blot for peNOS, ICAM, PERK 1/2, and P-16 as common markers for endothelial dysfunction as compared to control beta-actin.
Results:
Y-T2D (n=14, age 19.4±1.3y, BMI 38±9kg/m2) vs. (n=16, 40% female, age 22.9±2.6 y, BMI 23±3 kg/m2) had higher HbA1c (6.5 ± 1.2 vs 5.0 ± 0.5%), C-reactive protein (6.5±8.3 vs. 3.1±2.0 mg/L), systolic blood pressure (130±14 vs. 114±11 mmHg, all P< 0.05) but similar LDL-cholesterol and triglycerides. Y-T2D had greater CWT (1.34±0.13 vs. 1.22±0.13 mm, P=0.02) and impaired brachial and coronary arterial flow mediated dilatation (Figure 2). HCAECs incubated with Y-T2D exosomes induced phenotypic changes of endothelial dysfunction: reduced expression of phosphorylated endothelial nitric oxide synthase (peNOS), increased expression of endothelial membrane ICAM-1 and phosphorylation of pERK(1/2) (Figure 2).
Conclusion: Endothelial dysfunction in Y-T2D is evident using fmIHE cMRI setup showing exercise-induced coronary artery vasoconstriction in the absence of traditional risk factors including severe hyperglycemia, hypertension, or dyslipidemia. Plasma exosomes' phenotypical expressions confirmed the image findings of endothelial dysfunction and early vascular aging in Y-T2D.