Atherosclerosis In Minipigs Research Articles

Preliminary study of metabonomic changes during the progression of atherosclerosis in miniature pigs.

To explore potential biomarkers for early diagnosis of atherosclerosis (AS) and provide basic data for further research on AS, the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically. An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet. Fasting serum samples were collected monthly for metabolomics and serum lipid detection. At the end of the treatment period, pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS, thereby distinguishing the susceptibility of mini-pigs to AS. The metabolomics was detected using a high-resolution untargeted metabolomic approach. Statistical analysis was used to identify metabolites associated with AS susceptibility. Based on pathological analysis, mini-pigs were divided into two groups: a susceptible group (n = 3) and a non-susceptible group (n = 6). A total of 1318 metabolites were identified, with significant shifting of metabolic profiles over time in both groups. Dynamic monitoring analysis highlighted 57 metabolites that exhibited an obvious trend of differential changes between two groups with the advance of time. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis indicated significant disorders in cholesterol metabolism, primary bile acid metabolism, histidine metabolism, as well as taurine and hypotaurine metabolism. During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet, the alterations in serum metabolic profile exhibited a time-dependent pattern, accompanied by notable disturbances in lipid metabolism, cholesterol metabolism, and amino acid metabolism. These metabolites may become potential biomarkers for early diagnosis of AS.

Corilagin ameliorates atherosclerosis by regulating MMP-1, -2, and -9 expression in vitro and in vivo

Corilagin is a polyphenol has been identified anti-inflammatory properties. However, the anti-atherosclerotic effects of corilagin are not well understood. Here, we evaluated the anti-atherosclerotic effects and the underlying mechanisms of corilagin. We also verified whether corilagin can reverse atherosclerosis by regulating matrix metalloproteinase (MMP)-1, -2, and -9 in vitro and in vivo. An atherosclerosis model was established by feeding minipigs a high-fat diet combined with balloon injury, and the effects of different concentrations of corilagin on common carotid artery atherosclerosis in minipigs were monitored. Murine RAW264.7 macrophages were cultured and induced with oxidized low-density lipoprotein; fluorescence microscopy revealed the nuclear translocation of NF-κB. Furthermore, MMP-1, -2, and -9 expression in common carotid artery plaques and cellular models was detected by immunohistochemistry, western blotting, and RT-PCR. The pathological results suggested that the vascular intima of the model control group was significantly thickened, a large amount of collagen fibers was deposited, endothelial cells were damaged and detached, and plaque and foam cell formation occurred to varying degrees on the arterial wall, with lipid deposition. Corilagin treatment significantly reduced the degree of injury in the common carotid artery and decreased the number of lipid plaques and foam cells. Additionally, corilagin downregulated MMP-1, -2, and -9 expression in the common carotid artery plaques and cellular model. Moreover, corilagin significantly inhibited NF-κB nuclear translocation in vitro. Overall, corilagin exerted substantial therapeutic effects on experimental atherosclerotic minipigs via the downregulation of MMP-1, -2, and -9 expression.

Metabonomics Study of TCM Formula: Qutan Huayu Tongmai Granule as an Effective Treatment for Atherosclerosis in Mini-Pigs

To investigate the effects of QuTan HuaYu TongMai granule (QHTG) on the perturbed metabolism of atherosclerosis mini-pig model, a serum metabonomics method based on Liquid chromatography/mass spectrometry was developed. Principal component analysis and partial least squares-discriminate analysis models were established for the metabonomics analysis. The effect of high dose QHTG group is equivalent with those of positive drugs group in PCA score plots. Some significantly changed metabolites, including lyso-PCs, metabolites of vitamin D3 and fatty acids were found to be reasonable in explaining the anti-atherosclerosis mechanism of QHTG. Metabonomic approach is helpful to further understand the pathophysiology of atherosclerosis in mini-pigs and the therapeutic mechanism of QHTG. Our work also indicated that the LC–MS based metabonomics method is a potential tool for performing intervention and mechanism research of traditional Chinese medicine (TCM).

Medial elastic structure alterations in atherosclerotic arteries in minipigs: plaque proximity and arterial site specificity.

Using a model of atherosclerosis in minipigs, we analyzed changes in elastic structure within the medial sections of the abdominal aorta and left interventricular coronary artery both in the vicinity of and distal to atheromatous plaques. Twenty-four animals, divided into three groups, were fed either a control diet or a hypercholesterolemic and hyperhomocysteinic atherogenic diet, alone or in association with an antihypertensor, namely isosorbide dinitrate (Risordan). The atherogenic diet, administered for a period of four months, induced in the minipig advanced noncalcified atherosclerotic lesions that were histologically similar to those found in humans. A morphodensitometric analysis of the medial elastic structures was carried out on images obtained from specifically stained transverse arterial sections examined under a light microscope. The volume density of the elastic structures was diminished in the arterial media of the atherosclerotic animals due to opening and widening of the fenestrae in the elastic laminate and increased communication between the interlamellar spaces. Whereas this elastolytic process was uniform and independent of the proximity of atheromatous plaques in the left interventricular coronary artery, it was intensified in the vicinity of the plaques in the abdominal aorta. Overall elastolytic activity was increased in the walls of atheromatous artery in both arterial sites, and metalloproteinases were implied in this increase of activity. We previously reported that treatment with isosorbide dinitrate significantly reduced the moderate systolic hypertension and the increase in transparietal stress observed in the abdominal aorta of atheromatous animals. We report here that isosorbide dinitrate prevented the atherogenic-diet-induced deterioration of the elastic structure in these arteries; complete inhibition of changes to the elastic laminae was evident in areas remote from plaque formation, but only partial inhibition in the vicinity of such plaques. It did not, however, prevent structural damage in the left interventricular coronary artery or modify the increase in parietal elastolytic activity in either of the two arteries. This suggests that damage to the elastic structure in atheromatous arteries is dependent not only on overall elastolytic activity but also on localized factors, possibly related to parietal stresses, affected by the presence of atheromatous plaques.

The influence of atenolol and prazosin on serum lipids and atherosclerosis in minipigs fed a hyperlipidemic diet

1. 1. The effect of the adrenergic blockers prazosin and atenolol were tested in hypercholesterolemic Göttingen minipigs. 2. 2. After 1 yr there was a significant reduction of plasma triglycerides and total cholesterol in the medicated animals as compared to untreated ones. 3. 3. No significant difference in atherosclerotic lesions was observed.

Influence of nicotinic acid, niceritrol and β-pyridylcarbinol on experimental hyperlipidemia and atherosclerosis in mini-pigs

A study was undertaken to test for suitable conditions for examining the hypolipidemic and antiatherosclerotic actions of nicotinic acid, niceritrol and β-pyridylcarbinol in hypercholesterolemic mini-pigs. Hypercholesterolemia was produced in 50 female pigs by adding 11% dried egg yolk +0.5–0.75% cholesterol to their diet for 12–19 months. The animals were divided into 3 groups according to the response of their initial plasma cholesterol value (“low” ∼500; “medium” ∼700; “high” ∼1000 mg/100 ml). The plasma triglycerideconcentrations were increased in the latter two groups but not in the former. Most of the cholesterol was present in the LDL ( d = 1.006-1.063). In the medium group 0.5–0.75% of β-pyridylcarbinol or niceritrol in the diet produced a long-lasting and significant decrease of the plasma cholesterol concentration by about 150 mg/100 ml, predominantly by reducing the raised plasma LDL, whereas nicotinic acid produced only a transient decrease. In the “low”-cholesterol group, β-pyridylcarbinol and niceritrol also only produced a transient decrease. Atherosclerotic lesions developed in the coronary arteries and abdominal aorta of the “medium”- and “low”-cholesterol groups. Most of the increase of cholesterol esters took place in the intima. Niceritrol and β-pyridylcarbinol markedly reduced the lipid-infiltrated area of the abdomimal aorta and the accumulation of free and esterified cholesterol in the abdominal aorta and coronary arteries, whereas nicotinic acid was less effective in the latter respect. Part of the antiatherosclerotic action of β-pyridylcarbinol and niceritrol was due to their hypocholesterolemic effect. A more direct action on the vascular wall was probably also involved.