**Author details**

studied groups confirms some stable dynamic equilibrium of the factors concentrations. Probably, nonspecific effects of the factors in the studied ligand/receptor pairs on angiogen‐ esis processes are of somewhat conservative nature comprising prevention of excessive pro‐ tease activity, and sufficient for an adequate angiogenesis at the studied terms of pregnancy. However, use of these ratios is not informative to characterize the pathologic processes at studied terms in patients of these groups, excluding the ratio MMP‐9/TIMP‐1 at 11‐14 weeks of pregnancy. The observed reduction in MMP‐9/TIMP‐1 at 11‐14 weeks may serve as an alert

88 Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy

This study revealed the features of humoral systems regulating angiogenesis during physi‐ ological pregnancy and in patients with successful and unsuccessful perinatal outcomes. We found that deviations in the peripheral blood contents of angiogenesis‐related factors: VEGF‐ R1, VEGF‐R2, MMP‐9 and TIMP‐1 in patients with the history of missed abortion do not reflect critical for angiogenesis events in the first trimester of pregnancy. However, a significant dis‐ balance of soluble factors, regulating angiogenesis, detected in patients with missed abor‐ tion shows that matrix metalloproteinases and their tissue inhibitors play the leading role in pregnancy losses before 6 and 7–8 weeks. Analysis of ligand/receptor ratios complements the obtained results, as we have found a significant decrease in the VEGF/VEGF‐R1 and VEGF/ VEGF‐R2 ratios before 6 weeks of pregnancy despite the fact that there were no significant differences between individual molecules forming these pairs. The nature of VEGF/VEGF‐R1 and VEGF/VEGF‐R2 ratios alterations within the groups at the studied terms suggests the presence of a single mechanism that regulates interactions between VEGF and its receptors VEGF‐R1 and VEGF‐R2. In patients with pregnancy losses at 11‐14 weeks, we found low con‐ centrations of PLGF and sVEGF‐R1 and also of MMP‐2 and MMP‐9, and reduction in MMP‐2/ TIMP‐2 ratio, which are probably insufficient for an adequate angiogenesis at this term. Since an adequate angiogenesis is the determining factor for the development of pregnancy, early identification of criteria alerting about a trouble in fetoplacental system will also have diagnos‐ tic and prognostic value. Detection of the markers is especially important in cases of habitual pregnancy loss of unknown origin, because the disturbance of angiogenesis may be one of the causes of missed abortion. Taking into account difficulties with obtaining placental tissue at the studied terms of pregnancy, the angiogenesis‐related factors may serve as unbiased indi‐ cators of placental angiogenesis. The obtained results allow to presume various mechanisms of pregnancy pathology at early terms and to demonstrate the possibility of using the analysis

of ligand/receptor pairs to characterize the angiogenesis processes in early pregnancy.

The authors express their deep appreciation and gratitude to employee of Department of Perinatal Pathology, Kulikova G.V and the Department of Library and Information Resources

of the development of critical events.

**5. Conclusions**

**Acknowledgements**

Marina M. Ziganshina\*, Lyubov V. Krechetova, Lyudmila V. Vanko, Zulfiya S. Khodzhaeva, Ekaterina L. Yarotskaya and Gennady T. Sukhikh

\*Address all correspondence to: mmz@mail.ru

Federal State Budget Institution "The Research Center for Obstetrics, Gynecology and Perinatology" of the Ministry of Healthcare of the Russian Federation, Moscow, Russia

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## **Pathogenic Angiogenic Mechanisms in Alzheimer's Disease Pathogenic Angiogenic Mechanisms in Alzheimer's Disease**

Chaahat Singh, Cheryl G. Pfeifer and Wilfred A. Jefferies Chaahat Singh, Cheryl G. Pfeifer and Wilfred A. Jefferies

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/66403

#### **Abstract**

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Vascular dysfunction is a crucial pathological hallmark of Alzheimer's disease (AD). Studies have reported that beta amyloid (Aβ) causes increased blood vessel growth in the brains of AD mouse models, a phenomenon that is also seen in AD patients. This has given way to an alternative angiogenesis hypothesis according to which, increased leakiness in the blood vessels disrupts the blood‐brain barrier (BBB) and allows unwanted blood products to enter the brain causing progression of disease pathology, promoting amyloid clumping and aggregation along with impaired cerebral blood flow. Furthermore, the expression of melanotransferrin in AD model and patients may contribute to angiogenesis. The objective of this chapter is to attempt to establish a link between the vascular damage and AD pathology. Curbing the vascular changes and resulting damage seen in the brains of AD model mice and improving their cognition by treating with FDA‐approved anti‐angiogenic drugs may expedite the translational potential of this research into clinical trials in human patients. This direction into targeting angiogenesis will facilitate new preventive and therapeutic interventions for AD and related vascular diseases.

**Keywords:** Alzheimer's disease, amyloid beta, blood‐brain barrier, angiogenesis

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
