Atherosclerosis non transgenic mice high fat diet

In addition, HFFD led to impaired glucose and insulin response. It should be noted that this HFFD contained relative shortage of other components such as proteins and fibers compared to the standard chow diet.

CaMKII, which is activated in macrophages of advanced, but not early, mouse and human atherosclerotic lesions 92activates MK2. Advanced lesions refer to those which to contain a typical fibrotic cap and a lipid or necrotic core with or without calcification [ 14 ]. Moreover, in the context that obesity and type 2 diabetes are major risk factors for atherosclerotic cardiovascular disease — and a major reason why cardiovascular disease remains the leading cause of death 2 — a role for chronic inflammation and failed resolution in metabolic diseases is also emerging These combined data suggest that BLT1 signaling is important in early atherogenesis but that other proatherogenic processes become dominant in more advanced atherosclerosis.

Therefore, further animal models especially exhibiting the metabolic syndrome are necessarily needed Over time, the integrity of the fibrous cap may break down, leading to plaque rupture, which can trigger acute occlusive thrombosis and the associated clinical sequelae associated with tissue infarction 9 — In a cohort of patients from the Los Atherosclerosis non transgenic mice high fat diet Atherosclerosis Study, Dwyer and colleagues identified a variant allele of ALOX5 that was associated with increased carotid intima-media thickness.

Recent work has shown that regions of human atherosclerotic plaques characterized by large necrotic cores and thin fibrous caps had low levels of the pro-resolving mediator resolvin D1 RvD1 and high levels of the proinflammatory mediator LTB4 As mentioned above, the MerTK receptor can be inactivated by the metalloproteinase ADAM17, which cleaves the receptor and causes it to shed its soluble extracellular domain This may be not surprising because HFFD feeding did not induce remarkable obesity in rabbits.

We made a thorough evaluation of adipose tissue histology and did not find prominent increase of macrophage infiltration in the HFFD group compared to the control group.

Activation of these receptors leads to increased expression of inflammatory pathway enzymes, e. Analysis of aortic and coronary atherosclerosis The aorta and heart were isolated from each rabbit. Taken together, these results showed that the HFFD group exhibited insulin resistance.

This study describes a murine NASH model with distinct hepatic steatosis, inflammation and fibrosis, without renal pathology. It is also likely that these disorders exhibit a deleterious effect on insulin sensitivity thereby enhancing atherosclerosis.

Atherosclerosis in mice lacking apo E. Genetic factors controlling structure and expression of apolipoproteins B and E in mice. In response to an inflammatory stimulus, polyunsaturated fatty acids including AA, EPA, DHA, and DPA are released from phospholipids by phospholipase enzymes and then catalyzed by a series of lipoxygenases, namely, 5-lipoxygenase 5-LOXlipoxygenase LOXand lipoxygenase LOXto produce lipid mediators of inflammation and resolution The authors thank Gabrielle Fredman for her inspiration and insight related to many topics covered in this Review.

Phenotypic characterization of the Ath-1 gene controlling high density lipoprotein levels and susceptibility to atherosclerosis. J Clin Invest. On the one hand, we can consider the direct approach of administering exogenous SPMs, as discussed above.

Resolution of inflammation is not merely a passive return to homeostasis, but rather an active process mediated by specific molecules, including fatty acid—derived specialized pro-resolving mediators SPMs. Moreover, the pro-resolving protein IL also induces polarization of macrophages toward a pro-resolving phenotype with enhanced efferocytosis 76 A deeper understanding of the cellular mechanisms that promote atherosclerotic lesions, particularly the unique subset of advanced lesions that trigger vascular disease, may identify novel therapeutic targets to help stem this tide.

Figure S2. However, more mechanistic strategies must also be considered, and this will require a deeper understanding of how SPMs are synthesized and catabolized and how they work on effector cells to carry out various resolution processes.

Our understanding of the etiology of atherosclerosis has recently evolved to include failed resolution as a prominent causal feature for the most clinically relevant advanced plaques, opening up the exciting possibility that clinical plaque progression could be targeted in a manner that would lessen immunosuppression.

Cells found in the atherosclerotic lesion, including macrophages, T cells, and dendritic cells, promote expression of proinflammatory cytokines and eicosanoids that sustain proinflammatory responses 56.

Familial defective apolipoprotein B Parallel expression of the MB19 genetic polymorphism in apoprotein B and apoprotein B Briefly, more than adipocytes from each section were randomly measured for cellular diameter by two observers blindly, using an image analysis system Winroof ver 6.

Increased lipid cores and calcification in the lesions of the HFFD group indicate that the lesions become more vulnerable and more susceptible to complications. Conversely, plaque regions containing less necrosis and thicker fibrous caps demonstrated high levels of RvD1 and relatively lower levels of LTB4 Although the recent CANTOS trial has demonstrated that targeting inflammation can successfully reduce cardiac mortality in high-risk populations, it has also confirmed that antiinflammatory therapies run the risk of compromising host defense.

Probing the Genetics of Atherosclerosis in Transgenic Mice

Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. The ADAM17 effect is particularly interesting given that Mer proto-oncogene tyrosine kinase MerTKa key macrophage efferocytosis receptor in atherosclerotic lesions, is cleaved by this protease, resulting in defective lesional efferocytosis Plasma was collected from fasted animals and measured as described in the Methods.

One possibility would be to increase the precursors of SPMs through dietary supplementation of n-3 fatty acids. Thus, the CANTOS trial showed a beneficial effect of blocking inflammation independently of the role of lipids, highlighting the promise of therapy directed toward inflammation in cardiovascular disease.

Arterioscler Thromb.A mouse model of human familial hypercholesterolemia: markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet.

Nat Med. ; 4: – Crossref Medline Google Scholar; 7 Veniant MM, Pierotti V, Newland D, Cham CM, Sanan DA, Walzem RL, Young SG. Susceptibility to atherosclerosis in mice expressing exclusively apolipoprotein B48 or Cited by: The mouse has long been thought to be a poor model for studying human lipoprotein metabolism and atherosclerosis.

One of the major problems in using the mouse for these studies is that mice have significantly less total plasma cholesterol than do humans and do not develop atherosclerosis when fed the standard mouse chow diet containing 4% fat Author: Edward Rubin, Joshua Schultz.

Similarly, transgenic mice overexpressing 12/LOX on the Apoe –/– background and fed a chow diet showed attenuated atherosclerosis progression, which was thought to be due to increased 12/LOX–mediated synthesis of LXA 4.

The role of non-resolving inflammation in atherosclerosis

However, Merched and colleagues demonstrated that the role of 12/LOX in atherosclerosis is not by: Mice fed high-fat, high-cholesterol diets had a significantly higher incidence of gastritis than mice fed normal chow, 62% versus 5%, respectively (P,).

This effect was specific for LDLR 2/2 mice, because no. · ApoE −/− mice fed with high fat western diet (WD), enriched with cholesterol, over seven weeks, developed metabolic syndrome and showed: (i) fast development of steatosis, (ii) hepatocyte ballooning, (iii) high fasting glucose levels, (iv) inflammation, (v) with pronounced fibrosis, (vi) portal hypertension and (vii) no kidney by:  · Methods.

We fed Watanabe heritable hyperlipidemic (WHHL) rabbits with a high-fructose and high-fat diet (HFFD) with restricted normal calories and compared the lesions of both aortic and coronary atherosclerosis with those of control WHHL rabbits fed a normal chow diet.

Atherosclerosis non transgenic mice high fat diet
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