Angiotensin 1-7 formation in breast tissue is attenuated in breast cancer - a study on the metabolism of angiotensinogen in breast cancer cell lines.

The tissue renin-angiotensin system (RAS) plays an important role in the development and progression of many diseases. It has been confirmed that angiotensin II (ANG II) participates in the proliferation and angiogenesis of breast cancer. Moreover, some RAS dysregulations in cancer have been observed. Recent studies on the role of two opposite axes of angiotensinogen metabolism - ACE (angiotensin-converting enzyme)/ANGII/AT1R (angiotensin receptor type 1) and ACE-2/ANG 1-7/MAS (mitochondrial assembly) - indicate their importance in tumor growth and invasion, but studies describing the metabolic pathways in breast cancer and the role of newer angiotensins, such as ANG 1-12, remain lacking. In this study, the metabolism of angiotensinogen fragments in three breast cancer lines, namely, MDA-MB-231, MCF-7, and T-47D, compared with normal breast tissue cells (PCS-600) was estimated. Incubation of the cancer cells with angiotensinogen resulted in the prevalent formation of ANG 1-7. A difference in the ability to form ANG II was observed between cell lines. In normal breast cells, the strong predominance of the ACE-2/ANG 1-7/MAS pathway was detected. In cancer cells, differences in angiotensinogen metabolism depending on cancer line were observed; the prevalence of the ACE/ANG II/AT1R pathway was shown. Expressions of the RAS component were dysregulated in cancer cells and differed between cell lines. In conclusion, the ability of breast cancer cells to produce numerous angiotensin peptide metabolites was demonstrated. The metabolism of angiotensinogen differed between various types of breast cancer cells. The obtained results indicate the greater importance of the classical pathway - ACE/ANG II/AT1R - in breast cancer cells. The production of ANG 1-12 seems to be marginal in breast tissue, but a tendency for the higher formation of this peptide in cancer cells was observed. The production of ANG 1-7 was significantly lower in cancer cells, whereas the expression of MAS receptor was higher than that in the control. This finding suggests that substances with MAS receptor agonist activity could be useful in the treatment of breast cancer, but this requires further investigations.

Urocortin 2 in patients with hypertension treated with angiotensin converting enzyme inhibitors or angiotensin receptor blockers.

Urocortin 2 (Ucn2) - corticotropin-releasing hormone receptor 2 signalling has favourable effects in the cardiovascular system, including vasodilation, lowering of blood pressure and systemic peripheral resistance, increase in cardiac output and cardiac contractility, as well as cardioprotection against ischemia-reperfusion injury. Vasodilation and lowering of blood pressure seem to be very interesting and important effects, but their mechanism and interaction with the antihypertensive drugs have not been evaluated. The aim of the present study was to assess the relationship between Ucn2 concentration and antihypertensive therapy in patients with primary hypertension. We examined a group of 65 patients with primary hypertension receiving at least 3 antihypertensive drugs. In all of them plasma level of Ucn2, anthropometric measurements, biochemical tests, ambulatory blood pressure monitoring (ABPM), and echocardiography were performed. There were no differences in Ucn2 level related to beta-blockers, calcium channel blockers or diuretics, but we observed that in patients treated with angiotensin converting enzyme inhibitors (ACEI) (n = 52) serum Ucn2 levels were significantly higher than in patients treated with angiotensin-receptor blockers (ARBs) (n = 13) (10.93 versus 5.56 ng/mL; P < 0.05). Moreover, we did not observe any differences in terms of blood pressure on ABPM, biochemical measurements, left ventricular mass index, or presence of diabetes. In addition, in a small subgroup receiving alpha-blockers we also found a lower level of Ucn2, with coexisting higher systolic blood pressure at night, higher left ventricle mass index (LVMI) and more frequent occurrences of diabetes compared to non-alpha-blockers. Our findings suggest that the hypotensive action of renin-angiotensin-aldosterone system blockade may be related to the urocortin system. Ucn2 may be an important element in the mosaic of blood pressure-lowering factors in patients treated for essential hypertension.