Ischemia-Reperfusion Injury in Porcine Aortic Valvular Endothelial and Interstitial Cells

Jennie H Kwon; Miriam Atteya; Alekhya Mitta; Andrew D Vogel; Russell A Norris; Taufiek Konrad Rajab

doi:10.3390/jcdd10100436

Ischemia-Reperfusion Injury in Porcine Aortic Valvular Endothelial and Interstitial Cells

J Cardiovasc Dev Dis. 2023 Oct 19;10(10):436. doi: 10.3390/jcdd10100436.

Authors

Jennie H Kwon^{1

2}, Miriam Atteya¹, Alekhya Mitta³, Andrew D Vogel⁴, Russell A Norris², Taufiek Konrad Rajab⁵

Affiliations

¹ Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
² Department of Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
³ School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
⁴ Division of Research, Alabama College of Osteopathic Medicine, Dothan, AL 36303, USA.
⁵ Division of Pediatric Cardiovascular Surgery, Arkansas Children's Hospital, Little Rock, AR 72202, USA.

Abstract

Ischemia-reperfusion injury (IRI) in the myocardium has been thoroughly researched, especially in acute coronary syndrome and heart transplantation. However, our understanding of IRI implications on cardiac valves is still developing. This knowledge gap becomes even more pronounced given the advent of partial heart transplantation, a procedure designed to implant isolated human heart valves in young patients. This study aims to investigate the effects of IRI on aortic valvular endothelial cells (VECs), valvular interstitial cells (VICs), and whole leaflet cultures (no separation of VECs and VICs). We employed two conditions: hypoxic cold storage reperfusion (HCSR) and normothermia (NT). Key markers, secreted protein acidic and cysteine rich (SPARC) (osteonectin), and inducible nitric oxide synthase (iNOS2) were evaluated. In the isolated cells under HCSR, VICs manifested a significant 15-fold elevation in SPARC expression compared to NT (p = 0.0016). Conversely, whole leaflet cultures exhibited a 1-fold increment in SPARC expression in NT over HCSR (p = 0.0011). iNOS2 expression in VECs presented a marginal rise in HCSR, whereas, in whole leaflet settings, there was a 1-fold ascent in NT compared to HCSR (p = 0.0003). Minor escalations in the adhesion molecules intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), E-selection, and P-selection were detected in HCSR for whole leaflet cultures, albeit without statistical significance. Additionally, under HCSR, VICs released a markedly higher quantity of IL-6 and IL-8, with respective p-values of 0.0033 and <0.0001. Interestingly, the IL-6 levels in VECs remained consistent across both HCSR and NT conditions. These insights lay the groundwork for understanding graft IRI following partial heart transplantation and hint at the interdependent dynamic of VECs and VICs in valvular tissue.

Keywords: congenital cardiac surgery; ischemia reperfusion injury; partial heart transplantation; pediatric cardiac surgery; porcine; valve dysfunction; valvular endothelial cells; valvular interstitial cells.

Abstract

Grants and funding