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Examining the relationship between ischemic preconditioning and apoptosis and autophagy in ST-elevation vs. non-ST elevation acute myocardial infarction

Maclay, Lacey (2021) Examining the relationship between ischemic preconditioning and apoptosis and autophagy in ST-elevation vs. non-ST elevation acute myocardial infarction. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Introduction: Growing evidence suggests that the differences observed in symptomatology, morbidity, and mortality between ST-Elevation Acute Coronary Syndrome (STE-ACS) and Non-ST-elevation Acute Coronary Syndrome (NSTE-ACS) cannot be simply explained by the severity of coronary occlusion. Apoptosis and autophagy are two known pathways that can induce myocardial cell death or cell survival, respectively. Ischemic preconditioning, on the other hand, is a recognized endogenous protective mechanism that can limit the extent of scaring. It remains unknown if the degree of ischemic preconditioning, and subsequently the extent of apoptosis and autophagy, can partially explain the differences observed between STE-ACS and NSTE-ACS.
Methods: In this exploratory pilot study, we prospectively enrolled consecutive myocardial infarction (MI) patients from a single UPMC-affiliated primary PCI-receiving center. The interventional cardiologist obtained blood samples from each patient using PAX-gene tubes femoral arterial access line prior to the catheterization procedure. qRT-PCR were conducted using TaqMan assays, GAPDH as an endogenous control, and quantified using comparative Ct method. The following candidate genes were analyzed: BAX (apoptosis activator), BCL2 (apoptosis regulator), EGR1 (ischemic preconditioning suppressor), PINK1 (autophagy initiator), ATG5 (autophagy initiator), and DRAM2 (autophagy initiator).
Results: Our sample included 29 patients treated for acute MI (Age 67±12; 83% males). EGR1 was significantly correlated with DRAM2 (r=0.697, p<0.001), BCL-2 (r=0.657, p<0.001), and BAX (r=0.448, p<0.05). EGR1 was negatively associated with age and known history of CAD. Compared to patients with STE-ACS, those with NSTE-ACS had attenuated expression of EGR1 (4.7±2.2 vs. 6.9±0.7, p=0.001), BCL-2 (2.7±1.2 vs. 4.8±1.0, p=0.001), and BAX (–1.8±3.5 vs. 1.3±0.9, p=0.007). EGR1 was also more attenuated in patients with occlusion in left anterior descending or left circumflex coronary arteries.
Conclusions: Overall, these results indicate that ischemic preconditioning promotes more programmed cell death, which is more likely to happen in older patients and in those with existing CAD with progressive coronary occlusion primarily due to LAD or LCX occlusion. These are important and novel pilot results that may help explain the different clinical phenomena associated with STE-ACS vs. NSTE-ACS, which can inform future targeted therapies.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Maclay, Laceyljm97@pitt.eduljm97
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorAl-Zaiti, Salahssa33@pitt.edussa33
Committee CoChairFaramand, Ziadziadfaramand@pitt.eduziadfaramand
Committee MemberConley, Yvetteyconley@pitt.eduyconley
Committee MemberAl Ghouleh, Imadima6@pitt.eduima6
Committee MemberCarey, Marymary_carey@urmc.rochester.edu
Date: 19 April 2021
Date Type: Publication
Defense Date: 6 April 2021
Approval Date: 19 April 2021
Submission Date: 18 April 2021
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 32
Institution: University of Pittsburgh
Schools and Programs: University Honors College
School of Nursing > Nursing
Degree: BSN - Bachelor of Science in Nursing
Thesis Type: Undergraduate Thesis
Refereed: Yes
Uncontrolled Keywords: genomics, acute coronary syndrome
Date Deposited: 19 Apr 2021 15:49
Last Modified: 19 Apr 2021 15:49
URI: http://d-scholarship.pitt.edu/id/eprint/40656

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