Spontaneous atherosclerosis in the arterial system of ageing swine

Skold, Bernard Harold; Getty, R.; Ramsey, Fred L.

doi:10.31274/rtd-180813-4328

Cited by 43 publications

(43 citation statements)

References 26 publications

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“…Pigs spontaneously develop atherosclerosis and this is accelerated by feeding an atherogenic diet (13–15). The pig is large enough to allow for non-invasive measurements of arteries and for harvesting sufficient arterial tissue for analysis, has a human-like lipoprotein profile, and develops lesions in the coronary arteries.…”

Section: Animal Models Of Atherosclerosismentioning

confidence: 99%

Animal Models of Atherosclerosis

Getz

Reardon

2012

ATVB

521

357

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Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable.

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Section: Animal Models Of Atherosclerosismentioning

confidence: 99%

Animal Models of Atherosclerosis

Getz

Reardon

2012

ATVB

521

357

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“…Like humans, pigs are omnivores and the vascular response to the increase in fat content of the diet is similar. Indeed, elderly pigs can spontaneously develop atherosclerosis [6]. In this review, we will focus on four porcine models with accelerated atherosclerosis: the induced diabetic/hypercholesterolemic (DM/HC) swine model, the LDL receptor knock-out model (or Rapacz pig), the recently described PCSK9 gain-of-function mutant cloned pig, and the Ossabaw metabolic syndrome model (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia

Hamamdzic

Wilensky

2013

Journal of Diabetes Research

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Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral atherosclerosis offer several advantages over rodent models, including similar anatomical size to humans, as well as genetic expression and development of high-risk atherosclerotic lesions which are similar to humans. Here we review the four models of porcine atherosclerosis, including the diabetic/hypercholesterolemic model, Rapacz-familial hypercholesterolemia pig, the (PCSK9) gain-of-function mutant pig model, and the Ossabaw miniature pig model of metabolic syndrome. All four models reliably represent features of human vascular disease.

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“…Compared to humans, pigs not only have similar lipoproteins but also show similar morphology and biochemical composition in atherosclerosis plaque [9]. Moreover, the advantages of pig as a biomedical model for blood lipids also include: I. pigs can be raised in a unified and standard condition; II.…”

Section: Introductionmentioning

confidence: 99%

Genetic dissection of blood lipid traits by integrating genome-wide association study and gene expression profiling in a porcine model

et al. 2013

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BackgroundSerum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) are highly heritable traits that are used clinically to evaluate risk for cardiovascular disease in humans. In this study, we applied a genome-wide association study (GWAS) in 1,075 pigs from two populations and gene expression studies on 497 liver samples to dissect the genetic basis of serum lipids in a pig model.ResultsWe totally identified 8, 5, 2 and 3 genomic loci harboring 109 SNPs that were significantly associated with LDL-C, TC, TG and the ratio of HDL-C/LDL-C in two experimental populations, respectively. In the F2 population, the most prominent SNP was identified at the SSC3: 124,769,847 bp where APOB is the well-known candidate gene. However, in the Sutai population, the most number of significant SNPs was identified at SSC2: 64.97-82.22 Mb where LDLR was identified as the candidate gene. Furthermore, we firstly reported 4 novel genomic loci in pigs harboring the LDL-C-associated SNPs. We also observed obvious population heterogeneity in the two tested populations. Through whole-genome gene expression analysis, we detected 718 trait-correlated expressions. Many of these transcripts correspond to candidate genes for blood lipids in humans. The GWAS mapped 120 cis-eQTLs and 523 trans-eQTLs for these transcripts. One gene encoding the transcript gnl|UG|Ssc#S35330332 stands out to be an important candidate gene for LDL-C by an integrative analysis of GWAS, eQTL and trait-associated expression.ConclusionsWe identified the genomic regions or candidate genes associated with blood lipids by an integrative analysis of GWAS, QTT and eQTL mapping in pigs. The findings would benefit the further identification of the causative genes for blood lipid traits in both pigs and humans.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-14-848) contains supplementary material, which is available to authorized users.

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Spontaneous atherosclerosis in the arterial system of ageing swine

Cited by 43 publications

References 26 publications

Animal Models of Atherosclerosis

Animal Models of Atherosclerosis

Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia

Genetic dissection of blood lipid traits by integrating genome-wide association study and gene expression profiling in a porcine model

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