Background: Increase of blood pressure is accompanied by functional and morphological changes in the vascular wall. The presented study explored the effects of curcuma and black pepper compounds on increased blood pressure and remodeling of aorta in the rat model of experimental NO-deficient hypertension. Methods: Wistar rats were administered for 6 weeks clear water or L-NAME (40 mg/kg/day) dissolved in water, piperine (20 mg/kg/day), curcumin (100 mg/kg/day) or their combination in corn oil by oral gavage. The systolic blood pressure was measured weekly. Histological slices of thoracic aorta were stained with hematoxylin and eosin, Mallory's phosphotungstic acid hematoxylin (PTAH), orcein, picrosirius red and van Gieson staining and with antibodies against smooth muscle cells actin. Microscopic pictures were digitally processed and morphometrically evaluated. Results: The increase of blood pressure caused by L-NAME was partially prevented by piperine and curcumin, but the effect of their combination was less significant. Animals with hypertension had increased wall thickness and cross-sectional area of the aorta, accompanied by relative increase of PTAH positive myofibrils and decrease of elastin, collagen and actin content. Piperine was able to decrease the content of myofibrils and slightly increase actin, while curcumin also prevented elastin decrease. The combination of spices had similar effects on aortic morphology as curcumin itself. Conclusions: Administration of piperine or curcumin, less their combination, is able to partially prevent the increase of blood pressure caused by chronic L-NAME administration. The spices modify the remodeling of the wall of the aorta induced by hypertension. Our results show that independent administration of curcumin is more effective in preventing negative changes in blood vessel morphology accompanying hypertensive disease.
Matrix metalloproteinases (MMPs) are involved in cancer invasion and metastasis. Circulating tumor cells (CTCs) play role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. The aim of this study was to assess correlation between CTCs and tumor MMP1 in BC.
Cancer is a risk factor for venous thromboembolism (VTE) and plasma d‐dimer (DD) and tissue factor (TF) are established VTE associated markers. Circulating tumor cells (CTCs) are associated with the risk of VTE in metastatic breast cancer. This study aimed to correlate CTCs, blood coagulation and the urokinase plasminogen activator (uPA) system in primary breast cancer (PBC) patients. This prospective study included 116 PBC patients treated by primary surgery. CTCs were detected by quantitative RT‐PCR assay for expression of epithelial (CK19) or epithelial‐mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, ZEB1, FOXC2). Plasma DD, TF, uPA system proteins were detected by enzyme‐linked immunosorbent assays, while expressions of uPA system in surgical specimens were evaluated by immunohistochemistry. CTCs were detected in 27.6% patients. Patients with CTCs had a significantly higher mean plasma DD (ng/mL) than those of patients without CTCs (632.4 versus 365.4, p = 0.000004). There was no association between plasma TF and CTCs. Epithelial CTCs exhibit higher expression of uPA system genes compared to EMT_CTCs. Patients with CTCs had higher plasma uPA proteins than those of patients without CTCs; there was no correlation between tissue expression of uPA system, CTCs, DD or TF levels. In multivariate analysis CTCs and patients age were independent factors associated with plasma DD. We found association between plasma DD and CTCs indicating a potential role for activation of the coagulation cascade in the early metastatic process. CTCs could be directly involved in coagulation activation or increased CTCs could be marker of aggressive disease and increased VTE risk.
1 January 2017 in Oxidative Medicine and Cellular Longevity
Aronia melanocarpahas attracted scientific interest due to its dense contents of different polyphenols. We aimed to analyse effects ofAronia melanocarpa(AME) extract on blood pressure (BP), lipid peroxidation, cytokine level, total NOS activity in the left ventricle (LV), and aorta of L‐NAME‐induced hypertensive rats. 12‐week‐old male WKY rats were assigned to the control group and groups treated with AME extract (57.90 mg/kg/day), L‐NAME (40 mg/kg/day), or combination of L‐NAME (40 mg/kg/day) and AME (57.90 mg/kg/day) in tap water for 3 weeks. NOS activity, eNOS protein expression, and conjugated diene (CD) concentration were determined in the LV and aorta. After 3 weeks of L‐NAME treatment, BP was increased by 28% and concomitant treatment with AME reduced it by 21%. NOS activity of the LV and aorta in the L‐NAME group was decreased by about 40%, while AME increased it almost on the control level. AME‐induced eNOS upregulation may contribute to increase NOS activity. Moreover, AME decreased CD concentration in the LV and aorta and TNF‐αand IL‐6 production in the plasma were increased by L‐NAME treatment. In conclusion, our results showed that active substances ofAronia melanocarpamay have a positive effect on blood pressure, NOS activity, and proinflammatory processes in L‐NAME‐induced hypertension.