Endotracheal Exposure Of LPS Enhances Plaque Rupture In ApoE-KO Mice Fed With A Short-Term High Fat Diet

Author(s):  
Jen-erh (David) Jaw ◽  
Masashi Tsuruta ◽  
Yuexin Li ◽  
Sheena Tam ◽  
Yeni Oh ◽  
...  
Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Rani P Cruz ◽  
Wendy A Boivin ◽  
Ciara M Chamberlain ◽  
Jonathan C Choy ◽  
Bruce M McManus ◽  
...  

Introduction: Granzymes A and B (GrA/GrB) are cytotoxic proteases that are released by immune cells to eliminate target cells. GrB is present in human vessels and its expression corresponds to increased disease severity. In addition to their cytotoxic roles, in conditions of chronic inflammation, GrA and GrB may contribute to the degradation of extracellular matrix (ECM) proteins leading to tissue degeneration. Hypothesis: GrA and GrB levels are elevated in atherosclerotic patients and play a key role in the degradation of ECM and atherosclerosis. Methods: ApoE −/− x GrB −/− double knockout (apoE/GrB-DKO) mice were generated. C57-wt, GrB-KO, apoE-KO or apoE/GrB-DKO mice were fed a high fat diet for 30 weeks, sacrificed, tissues processed and lesion morphology and morphometry assessed. GrA and GrB levels were also measured in human plasma from patients with or without clinically evident atherosclerosis by ELISA. GrA/GrB-mediated ECM proteolytic activity was also assessed. Results: GrB deficiency significantly reduced the development of xanthomatosis, hair loss and atherosclerosis in the apoE-KO mice. GrB deficiency resulted in a marked reduction of elastin degradation in both the skin and blood vessels. GrB was found to co-localize to elastin fibres in atherosclerotic plaques and was capable of binding to, and cleaving elastin in vitro. ECM cleavage assays demonstrated that GrA and GrB cleave other ECM such as fibronectin. Preliminary studies indicate that GrB deficiency increases the lifespan of the apoE-KO mice as the apoE/GrB-DKO mice can survive up to 60 weeks of age on a high fat diet with no external indication of disease, skin degeneration or hair loss. In humans, preliminary evidence indicates that GrA/GrB levels are elevated in atherosclerosis. Smoking also appears to elevate plasma granzyme levels. Conclusions: During chronic inflammation, granzymes accumulate extracellularly and exhibit proteolytic activity towards extracellular matrix proteins that results in vascular remodeling and atherosclerosis with age. Attenuation of GrB resulted not only in a significant reduction of atherosclerosis, but also prolonged the lifespan of apoE-KO mice.


2005 ◽  
Vol 332 (1) ◽  
pp. 142-148 ◽  
Author(s):  
Anthony G. Passerini ◽  
Congzhu Shi ◽  
Nadeene M. Francesco ◽  
Peiying Chuan ◽  
Elisabetta Manduchi ◽  
...  

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Kathleen Axen ◽  
Marianna A. Harper ◽  
Yu‐Fu Kuo ◽  
Kenneth Axen

2017 ◽  
Vol 52 (3) ◽  
pp. 174
Author(s):  
Purwo Sri Rejeki ◽  
Harjanto Harjanto ◽  
Raden Argarini ◽  
Imam Subadi

The aim of this study was to determine the comparative effects of EA (EA) on the CV12, ST36 and ST40 to weight gain prevention over the short-term regulation of energy balance. The study was conducted with a completely randomized design. Rats were divided into five groups: negative control group (no treatment, n=5), positive control (sham EA/back, n=5), EA CV 12 (n=6), EA ST 36 (n=6) and EA ST 40 (n=7). Rats were exposed to high-fat diet for two weeks and EA was simultaneously performed once daily, five days a week for two weeks with 2 Hz, for 10 minutes with continuous wave. Body weight, BMI, front limb circumference and rear were measured during study. Levels of blood glucose, cholesterol, triglycerides, LDL and HDL were measured at the end of the study; which reflects the short-term regulation of energy homeostasis. For weight loss, EA CV12, ST36 and ST40 group have lost weight significantly compared to the negative and positive control group. The ST40 group has a significant decrease than ST36 and CV12. The most significant decrease in BMI found in the ST40 group. EA did not affect blood glucose levels, but modulated blood lipid profile. In ST 40 group there was a significant decrease in cholesterol, LDL and triglycerides. EA at point ST 40 is potential in preventing increased body weight and BMI in rats exposed to high-fat diet compared to the CV 12 and ST 36. ST 40 is a point with a potential of lowering LDL and triglycerides serum so that it can play a role in the short term regulation of energy homeostasis but also in the prevention of dyslipidemia.


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