scholarly journals Effect of Dysferlin Deficiency on Atherosclerosis and Plasma Lipoprotein Composition Under Normal and Hyperlipidemic Conditions

2021 ◽  
Vol 12 ◽  
Author(s):  
Zoe White ◽  
Nadia Milad ◽  
Stephanie L. Sellers ◽  
Pascal Bernatchez

Dysferlinopathies are a group of muscle disorders caused by mutations to dysferlin, a transmembrane protein involved in membrane patching events following physical damage to skeletal myofibers. We documented dysferlin expression in vascular tissues including non-muscle endothelial cells, suggesting that blood vessels may have an endogenous repair system that helps promote vascular homeostasis. To test this hypothesis, we generated dysferlin-null mice lacking apolipoprotein E (ApoE), a common model of atherosclerosis, dyslipidemia and endothelial injury when stressed with a high fat, and cholesterol-rich diet. Despite high dysferlin expression in mouse and human atheromatous plaques, loss of dysferlin did not affect atherosclerotic burden as measured in the aortic root, arch, thoracic, and abdominal aortic regions. Interestingly, we observed that dysferlin-null mice exhibit lower plasma high-density lipoprotein cholesterol (HDL-C) levels than their WT controls at all measured stages of the disease process. Western blotting revealed abundant dysferlin expression in protein extracts from mouse livers, the main regulator of plasma lipoprotein levels. Despite abnormal lipoprotein levels, Dysf/ApoE double knockout mice responded to cholesterol absorption blockade with lower total cholesterol and blunted atherosclerosis. Our study suggests that dysferlin does not protect against atherosclerosis or participate in cholesterol absorption blockade but regulates basal plasma lipoprotein composition. Dysferlinopathic patients may be dyslipidemic without greater atherosclerotic burden while remaining responsive to cholesterol absorption blockade.

2006 ◽  
Vol 366 (1-2) ◽  
pp. 309-315 ◽  
Author(s):  
Jyrki J. Ågren ◽  
Maarit Hallikainen ◽  
Helvi Vidgren ◽  
Tatu A. Miettinen ◽  
Helena Gylling

Dietary Fiber ◽  
1986 ◽  
pp. 309-321 ◽  
Author(s):  
Barbara Olds Schneeman ◽  
Michael Lefevre

1997 ◽  
Vol 3 (S2) ◽  
pp. 829-830
Author(s):  
R.J. Dempsey ◽  
R.G. Buice ◽  
W.C. Symons ◽  
R.A. Lodder

Accurate and nondestructive measurement of different lipoproteins simultaneously in carotid plaque in stroke patients using near-infrared (IR) imaging spectrometry seems possible for research. The lipoprotein composition of the plaque appears to have an impact on the outcome of the disease process. Carotid atherosclerosis without associated thrombosis is frequently a benign disease that is asymptomatic, although TIAs may be present in other cases. Many patients with carotid atherosclerosis can be treated surgically by endarterectomy with high initial success and favorable long-term prognosis. The acute manifestation of carotid atherosclerosis - stroke - arises when thrombus or ulceration develop. This potentially life-threatening complication probably develops at the site of plaque fissure or rupture. Recent research by others indicates that it is not the severity of stenosis (plaque volume) that determines the outcome: it is the type of stenosis (plaque chemical composition) and the extent of collateral growth.


1989 ◽  
Vol 119 (6) ◽  
pp. 857-863 ◽  
Author(s):  
Denise M. Ney ◽  
John B. Lasekan ◽  
Junghee Kim

2005 ◽  
Vol 73 (10) ◽  
pp. 6283-6289 ◽  
Author(s):  
Takeshi Matsuzawa ◽  
Asaomi Kuwae ◽  
Akio Abe

ABSTRACT Enteropathogenic Escherichia coli (EPEC) delivers a subset of effectors into host cells via a type III secretion system. Here we show that the type III effector EspG and its homologue EspG2 alter epithelial paracellular permeability. When MDCK cells were infected with wild-type (WT) EPEC, RhoA was activated, and this event was dependent on the delivery of either EspG or EspG2 into host cells. In contrast, a loss of transepithelial electrical resistance and ZO-1 disruption were induced by infection with an espG/espG2 double-knockout mutant, as was the case with the WT EPEC, indicating that EspG/EspG2 is not involved in the disruption of tight junctions during EPEC infection. Although EspG- and EspG2-expressing MDCK cells exhibited normal overall morphology and maintained fully assembled tight junctions, the paracellular permeability to 4-kDa dextran, but not the paracellular permeability to 500-kDa dextran, was greatly increased. This report reveals for the first time that a pathogen can regulate the size-selective paracellular permeability of epithelial cells in order to elicit a disease process.


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