The influence of different diets on metabolism and atherosclerosis processes-A porcine model: Blood serum, urine and tissues 1H NMR metabolomics targeted analysis.

The global epidemic of cardiovascular diseases leads to increased morbidity and mortality caused mainly by myocardial infarction and stroke. Atherosclerosis is the major pathological process behind this epidemic. We designed a novel model of atherosclerosis in swine. Briefly, the first group (11 pigs) received normal pig feed (balanced diet group-BDG) for 12 months, the second group (9 pigs) was fed a Western high-calorie diet (unbalanced diet group-UDG) for 12 months, the third group (8 pigs) received a Western type high-calorie diet for 9 months later replaced by a normal diet for 3 months (regression group-RG). Clinical measurements included zoometric data, arterial blood pressure, heart rate and ultrasonographic evaluation of femoral arteries. Then, the animals were sacrificed and the blood serum, urine and skeletal muscle tissue were collected and 1H NMR based metabolomics studies with the application of fingerprinting PLS-DA and univariate analysis were done. Our results have shown that the molecular disturbances might overlap with other diseases such as onset of diabetes, sleep apnea and other obesity accompanied diseases. Moreover, we revealed that once initiated, molecular changes did not return to homeostatic equilibrium, at least for the duration of this experiment.

Adventitial lymphatics of internal carotid artery in healthy and atherosclerotic vessels.

OBJECTIVES: Presence of lymphatics in adventitia of major arteries remains controversial. Presence of lymphatics in adventitia of internal carotid artery was not documented and its relation to atherosclerosis was not studied. The aim of our study was to evaluate presence of lymphatic vessels in adventitia of internal carotid artery in healthy and atherosclerotic arteries. METHODS: Fragments of arterial wall of internal carotid artery were obtained during the surgical eversion endarterectomy in 15 patients with internal carotid artery stenosis and 2 healthy organ donors. 21 arteries were studied. Patients age ranged from 56 to 77 years. Fragments of arterial wall were embeded in paraffin. Lymphatics of arterial adventitia were visualized with immunohistochemistry using LYVE-1 and anty-podoplanin antibodies. RESULTS: The lymphatic vessels were visualized in adventitia of 20 carotid arteries. The serial sections have revealed that both LYVE-1 and podoplanin have identical specificity for lymphatic endothelium Number of lymphatics in adventitia significantly correlated with thickness of intima (p<0.046). CONCLUSIONS: Lymphatics are present in adventitia of internal carotid artery. Number of adventitial lymphatics increases with severity of atherosclerosis measured as intimal thickness.

Expression of collagenase-1 (MMP-1), collagenase-3 (MMP-13) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in laryngeal squamous cell carcinomas.

Matrix metalloproteinases (MMPs) that have a proteolytic activity against the components of extracellular matrix (ECM) play an important role in the invasive and metastatic spread of tumors. The role of MMPs and tissue inhibitors of MMPs (TIMPs) in laryngeal squamous cell carcinoma (LSCC) has not been elucidated sufficiently. The aim of the present study was to evaluate the correlation between the expression of collagenase-1 (MMP-1), collagenase-3 (MMP-13) and TIMP-1, as well as the clinicopathological features of LSCCs. The expression of collagenases and TIMP-1 was examined immunohistochemically in 50 cases of surgically obtained specimens of primary LSCCs. Analyses indicated that LSCC cells as well as stromal cells expressed MMP-1, MMP-13 and TIMP-1 immunostaining. Overexpression of TIMP-1 occurred more frequently in non-metastasizing cases (P=0.009). TIMP-1 and MMP-1 staining correlated significantly with the histologic type of LSCC. The keratinizing type of carcinomas exhibited higher TIMP-1 protein expression than the nonkeratinizing variety (P=0.01). TIMP-1 staining was associated with the grade of differentiation, since it was found predominantly in well and moderately differentiated carcinomas (P=0.04). The findings confirm that expression of analyzed MMPs and TIMP-1 is characteristic of LSCC and that these enzymes contribute to the progression of tumors. TIMP-1 upregulation might exhibit lower metastatic potential in LSCCs and is linked rather with an early stage of tumor progression. It seems also that TIMP-1 expression is dependent on the grade of differentiation.