Impact of Subclinical Leaflet Thrombosis on Valve Hemodynamic Consequences and Structural Valve Deterioration after Transcatheter Aortic Valve Replacement

Background: The effect of subclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT), on the valve hemodynamic function and durability of the bioprosthetic valve has not been yet determined. OBJECTIVES: This study aimed to determine the impact of HALT on valve hemodynamics detected by serial echocardiography after transcatheter aortic valve replacement (TAVR). METHODS: The ADAPT-TAVR trial is a multicenter, randomized trial that compared edoxaban and dual antiplatelet therapy in patients without an indication for anticoagulation who had undergone successful TAVR. The presence of HALT was evaluated by four-dimensional computed tomography (CT) at 6 months and serial echocardiography performed at baseline, immediately post-TAVR, and after 6 months of follow-up. The relationship of HALT with valve hemodynamics and hemodynamic structural valve deterioration (SVD) was assessed. RESULTS: At 6 months, HALT was found in 30 of 211 (14.2%) patients with evaluable cardiac CT scans. The presence of HALT did not significantly affect mean aortic valve mean gradients (with vs. without HALT; 14.0 ± 4.8 mmHg vs. 13.7 ± 5.5 mmHg; p=0.742) and mean aortic valve area (1.64 ± 0.44 cm2 vs. 1.54 ± 0.36 cm2; p=0.208) at 6 months. No significant baseline predictors were noted for HALT at 6 months. At least moderate hemodynamic SVD was reported in 30 of 206 patients (14.6%) at the time of the echocardiography at 6-month follow-up echo. The use of aortic valve size ≤ 23 mm and smaller aortic valve area were independent predictors of the development of hemodynamic structural valvular dysfunction; however, the presence of HALT was not identified as a predictor of hemodynamic SVD. CONCLUSIONS: In patients who had undergone successful TAVR, aortic valve hemodynamic status was not influenced by the presence of HALT. Although HALT was not a predictor of hemodynamic SVD at 6 months, it warrants further longer-term follow-up studies are warranted to evaluate the impact of valve durability and also this study was not powered for clinical outcomes.Maste

Identification and functions of PSV(Protein Storage Vacuoles) - type compartment in Arabidopsis mature leaves.

1

단백질 저장과 병원균 방어를 위한 식물 단백질 수송 경로들의 기능적 다양성 연구

DoctorAll living organisms growing under ever-changing environmental conditions must have mechanisms to cope with such changes. The molecular machineries for responses to the environmental challenge are different from or sometime even incompatible with those for the normal growth. Animals have developed strategy using specialized cell-types, for the responses, for example, immune-specific cells for biotic stress, a major environmental challenge. In contrast, in plants with no immune-specific cells, the vegetative cells undergoing growth have to respond when challenged by biotic stress. However, it remains unknown how the plant cell efficiently readjust its molecular machineries between growth and environmental stress responses at the cellular level. Here, I provide evidence that plant cells use a strategy of bifurcated vacuolar protein trafficking system consisting of the NtSS (N-terminal sorting signal) and CtSS (C-terminal sorting signal) pathways for effective distribution of the molecular machineries required for growth and defense response, respectively. There are two vacuolar sorting pathways, NTPP (N-terminal propeptide) and CTPP (C-terminal propeptide) in plant cells. The NTPP pathway is mainly involved in sorting of proteins into lytic vacuoles for degradation in adult tissues, while the CTPP pathway mediates transport of proteins into Protein Storage Vacuole (PSV) for storage in seeds. NTPP sorting sequence has NPIR-like motif and CTPP is composed of hydrophobic amino acids but not conserved. In this study, I reveal that two potential CTPP motifs are identified by using sequence-based computational tool. Interestingly, potential CTPP motifs are highly enriched in pathogen-related (PR) proteins among vacuolar and secretory proteins. Especially, putative CTPP motifs are mainly discovered in defensins (PR-12 family), thionins (PR-13 family), lipid transfer proteins (LTP/PR-14 family) and chitinase. Next, I show that CtSS-containing PR genes, PDF1:1, PDF3:1 and CHIA1, are stored in certain compartment where GFP:CT24, a representative seed CTPP marker, is accumulated. Interestingly, SYP22, a Q-SNARE surrounds membrane of GFP:CT24-positive compartments in vegetative tissue. Using vesicle trafficking assay with vesicle trafficking-defective mutant plants, I reveal that VTI11, EpsinR1, AP1 adaptor complex and VPS35A coordinate with NtSS pathway, but VTI12, EpsinR2, SYP22, AP-3 adaptor complex and VPS35B/C are involved in CtSS pathway. Besides, I discover that CtSS – containing CHIA1 and GFP:CT24 are strongly accumulated and secreted into infection site via vesicle-mediated pathway upon G. orontii fungal inoculation. Interestingly, I provide that vps35 mutants required for CtSS pathway display more susceptibility than WT against B.g.h and E. PISI penetration. Taken together, the vegetative NtSS pathway is largely responsible for the vacuolar trafficking, leading to protein degradation during normal developmental growth. By contrast, the CtSS pathway is largely responsible for trafficking of the pathogen-related proteins such as defensins and acidic chitinase to a novel compartment, named vCPC (vegetative CtSS protein compartment). The vCPC normally fuses to the lytic vacuole for steady-state regulation of proteins. However, upon fungal infection, PR proteins stored in the vCPC are secreted specifically to the encasement of haustorium. Therefore, I propose that the strategy for biotic stress responses is drastically different between plants and animals at the whole organism level but shows striking similarities at the cellular level, which is resulted from convergent evolution

놀이 담화의 교육적 효용에 대한 연구

학위논문(석사)--서울대학교 대학원 :국어교육과 국어교육 전공,2006.Maste

The C-Terminal region of beta-glucanse is important for targeting to the Protein Storage Vacuole.

2

Beta-glucosidase homologs in homeostasis of ABA levels in arabidopsis.

1

Identification and Function of Protein Storage Vacuoles in Mature Leaves.

2

Studies on the fusion mechanism of protein storage vacuole during germination in Arabidopsis.

2