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Full-Text Articles in Medicine and Health Sciences
The Role Of Dlc1Β In Attenuating Cardiac Ischemia-Reperfusion Injury During Heart Transplantation, Samantha L. Collings
The Role Of Dlc1Β In Attenuating Cardiac Ischemia-Reperfusion Injury During Heart Transplantation, Samantha L. Collings
Electronic Thesis and Dissertation Repository
Cardiac ischemia-reperfusion injury (IRI) occurs intra-operatively during heart transplantation (HTx), underpinning graft survival. Past research implicated the PI3K/Akt1 & RhoA/ROCK pathways in IRI. Rho-GTPase activity/Akt regulates Deleted-in-liver-cancer 1 protein’s beta-isoform (DLC1β). Therefore, we hypothesized that DLC1β overexpression (OE) had anti-apoptotic effects. In vitro, HL-1 cells (mouse cardiomyocytes) received chamber hypoxia-oxygenation reperfusion (H/R) for 24H4R with/without DLC1β plasmid, before collection for protein/mRNA analyses. DLC1β-OE resulted in downregulated pro-apoptotic mRNA expression (Bax/Cycs/Casp3), upregulated protective mRNA targets (BCl2/Akt1) and less late/early apoptosis via flow cytometry. Results were confirmed via H9C2 (rat cardiomyocyte) cell lines. In vivo, C57/BL6 mice received heterotopic HTx with/without DLC1β-OE …
Acidic Ph Environment Alters Cell Death And Regulates Aif Translocation In Endothelial Cells, Laura Xu
Acidic Ph Environment Alters Cell Death And Regulates Aif Translocation In Endothelial Cells, Laura Xu
Electronic Thesis and Dissertation Repository
Cardiac transplantations are the golden standard treatment for end-stage heart failure but issues like ischemia-reperfusion injury (IRI) and graft rejection persist. Prolonged ischemia induces anaerobic metabolism, lactic acid accumulation, and intracellular acidosis. IRI is associated with programmed cell death, of which necroptosis is significant. We have shown that in hypoxia-reoxygenation, targeting necroptosis prevents murine microvascular endothelial cell (MVEC) death through cyclophilin D inhibition in vitro and apoptosis-inducing factor (AIF) is implicated in DNA damage. Here, we investigated AIF and the impact of acidic pH on cell death. Acidic pH conditions altered MVEC necroptosis to an apoptosis-like pattern. AIF nuclear translocation …
Angiogenesis And Neo-Microcirculatory Function In Diseased Tissue Revealed By Intravital Microscopy, Giovanni-Michele Arpino
Angiogenesis And Neo-Microcirculatory Function In Diseased Tissue Revealed By Intravital Microscopy, Giovanni-Michele Arpino
Electronic Thesis and Dissertation Repository
Angiogenesis is the process of generating new blood microvessels. In adults, angiogenesis is fundamental to tumor biology and also to tissues rendered ischemic from vascular occlusion. Despite a promising appeal, strategies designed to simulate or otherwise modify the angiogenic process in adult tissues have yet to realize significant therapeutic potential. Importantly, understanding the structure and function of new microvascular networks formed in adult, diseased tissues is limited. In fact, it remains unknown if a new or regenerated microcirculation can effectively deliver oxygen to the tissue. The purpose of this thesis was to seek out novel determinants of functional angiogenesis and …