The role of pro- and antiangiogenic factors in angiogenesis process by Raman spectroscopy

Raman spectroscopy and Raman imaging are powerful techniques to monitor biochemical composition around blood vessel. The aim of this study was to understand the role of pro- and antiangiogenic factors in angiogenesis process. Raman imaging and Raman single spectrum measurements allow the diagnosis of cancer biochemical changes in blood vessel based on several biomarkers simultaneously. We have demonstrated that Raman imaging combined with statistical methods are useful to monitoring pro- and antiangiogenic factors responsible for angiogenesis process. In this paper Raman markers of proangiogenic and antiangiogenic factors were identified based on their vibrational signatures. Obtained results can help understand how growing tumor create its vascular system.

Pro- and Antiangiogenic Factors in Gliomas: Implications for Novel Therapeutic Possibilities

Angiogenesis, a complex, multistep process of forming new blood vessels, plays crucial role in normal development, embryogenesis, and wound healing. Malignant tumors characterized by increased proliferation also require new vasculature to provide an adequate supply of oxygen and nutrients for developing tumor. Gliomas are among the most frequent primary tumors of the central nervous system (CNS), characterized by increased new vessel formation. The processes of neoangiogenesis, necessary for glioma development, are mediated by numerous growth factors, cytokines, chemokines and other proteins. In contrast to other solid tumors, some biological conditions, such as the blood–brain barrier and the unique interplay between immune microenvironment and tumor, represent significant challenges in glioma therapy. Therefore, the objective of the study was to present the role of various proangiogenic factors in glioma angiogenesis as well as the differences between normal and tumoral angiogenesis. Another goal was to present novel therapeutic options in oncology approaches. We performed a thorough search via the PubMed database. In this paper we describe various proangiogenic factors in glioma vasculature development. The presented paper also reviews various antiangiogenic factors necessary in maintaining equilibrium between pro- and antiangiogenic processes. Furthermore, we present some novel possibilities of antiangiogenic therapy in this type of tumors.

Prenatal Low-Dose Aspirin Use Associated with Reduced Incidence of Postpartum Hypertension among Women with Preeclampsia

Objective Postpartum hypertension (PP-HTN), defined as systolic/diastolic blood pressure (SBP/DBP) ≥140/90, on two occasions at least 4 hours apart after delivery occurs in up to 50% of preeclamptic pregnancies, and is associated with adverse maternal outcomes. Excessive production of antiangiogenic factors (i.e., soluble fms-like tyrosine kinase 1 [sFLT1]) and reduced levels of proangiogenic factors (i.e., placental growth factor [PlGF]) are associated with preeclamptic pregnancies. The aim of this study was to identify clinical risk factors and/or serum biomarkers associated with PP-HTN in preeclampsia. Study Design Preeclamptic women (n = 82, aged ≥18 years) were prospectively enrolled in an observational study. Serial blood pressures were obtained through the labor course and until 48 hours postpartum, and serum was obtained within 24 hours postpartum. Statistical analysis was performed by using Student's two-tailed t-test and Fisher's exact test. Results Baseline comorbidities and antihypertensive use were similar among those who developed PP-HTN and those who did not. Among preeclamptic patients, 33% developed PP-HTN; these had significantly more severe preeclampsia features versus no PP-HTN (96 vs. 78%, p = 0.05). PP-HTN was associated with higher re-hospitalization rates (26 vs. 6%, p = 0.01). Among those taking low-dose aspirin (ASA) for preeclampsia prophylaxis (n = 12), PP-HTN was significantly less frequent versus those not taking low-dose ASA (0 vs. 22%, p = 0.007). Low-dose ASA use was associated with significantly lower peripartum sFLT1 levels (4,650 ± 2,335 vs. 7,870 ± 6,282 pg/mL, p = 0.03) and sFLT1/PlGF ratio (397 ± 196 vs. 1,527 ± 2,668, p = 0.03). Conclusion One-third of women with preeclampsia develop PP-HTN; these patients have more severe preeclampsia and have higher re-hospitalization rates. Prenatal low-dose ASA use was associated with significantly lower incidence of PP-HTN, reduced levels of antiangiogenic factors, and lower 6-week re-hospitalization rates. These findings, if replicated, may have clinical implications on the use of low-dose ASA during pregnancy to reduce incidence of postpartum HTN. Key Points

Peripartum cardiomyopathy: epidemiology, pathophysiology, and management

The article summarizes the current knowledge on epidemiology, pathophysiology, and management of patients with peripartum cardiomyopathy. The incidence of peripartum cardiomyopathy varies and largely depends on the geographic region. The overall mortality reaches up to 4-28%. Risk factors for developing peripartum cardiomyopathy include multiple pregnancies and multiple births, family history, smoking, diabetes mellitus, hypertension, preeclampsia, poor nutrition, older or adolescent maternal age, and long-term treatment with beta-adrenergic agonists. Genetic factors play the leading role in the pathophysiology of peripartum cardiomyopathy. It is generally confirmed by family history and the incidence variation depending on the geographical region. The pathogenetic role of vasoinhibin, an isoform of prolactin, is described. Vasoinhibin has antiangiogenic, proapoptotic, proinflammatory, and vasoconstrictor effects. The important role of an imbalance between angiogenic and antiangiogenic factors is discussed. There are no guidelines for obstetricians and gynecologists on the management of pregnant women, parturient women, and postpartum women. One of the reasons is the absence of evidence. An urgent cesarean section is indicated if the pregnant woman has acute heart failure and requires inotropic support and/or invasive therapy. However, 2018 ESC Guidelines for the Management of Cardiovascular Diseases during Pregnancy recommend vaginal delivery in these patients.

Outcomes of pregnancies in women with extremely high ratio of sFlt-1 / PlGF: a series of clinical cases

Preeclampsia as one of the manifestations of placental dysfunction associated with dysregulation of pro- and antiangiogenic factors. During normal pregnancy, the concentration of antiangiogenic factor sFlt-1 remains low, which allows accurate transmission of signals induced by proangiogenic factors VEGF and PlGF. This balance is crucial to maintain physiological vasodilation. Under hypoperfusion, the placenta increases the synthesis of sFlt-1, trying to increase maternal pressure and increase placental perfusion.The objective: to study the clinical outcomes of pregnancies in a group with extremely high ratios of sFlt-1 and PlGF.Materials and methods. The results of determining the levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sfLT-1), which were performed during 2017-2020 in the serum of 128 pregnant women at 18–39 weeks, were analyzed.Results. The mean age of pregnant women was 28,4±4 years. The average gestational age during the study was 26±5 weeks. The majority of pregnant women had signs of IUGR (62,5%) and/or preeclampsia (50%) during the study. The average level of the sFlt/PIGF ratio was 1747 pg/ml. In 100% of cases with a digital ratio of more than 850, signs of an obstetric angiogenic catastrophe that required immediate delivery developed during the nearest future. The average time from analysis to delivery was 10 days. In 50% of pregnant women, urgent delivery was required within 48 hours after analysis. Favorable neonatal results were observed in 37,5% of women.Conclusion. We found a tendency for worsening perinatal outcomes in women with extremely high sFlt-1/PlGF ratios after reaching 850. Careful monitoring of the pregnant woman and consideration of need for prophylactic administration of corticosteroids to accelerate fetal lung maturation in this group is rational.

Immunology and Pathology in Ocular Drug Development

Clear vision is dependent on features that protect the anatomical integrity of the eye (cornea and sclera) and those that contribute to internal ocular homeostasis by conferring hemangiogenic (avascular tissues and antiangiogenic factors), lymphangiogenic (lack of draining lymphatics), and immunologic (tight junctions that form blood–ocular barriers, immunosuppressive cells, and modulators) privileges. The later examples are necessary components that enable the eye to maintain an immunosuppressive environment that responds to foreign invaders in a deviated manner, minimizing destructive inflammation that would impair vision. These conditions allowed for the observations made by Medawar, in 1948, of delayed rejection of allogenic tissue grafts in the anterior chamber of mouse eye and permit the sequestration of foreign invaders (eg, Toxoplasma gondii) within the retina of healthy individuals. Yet successful development of intraocular drugs (biologics and delivery devices) has been stymied by adverse ocular pathology, much of which is driven by immune pathways. The eye can be intolerant of foreign protein irrespective of delivery route, and endogenous ocular cells have remarkable plasticity when recruited to preserve visual function. This article provides a review of current understanding of ocular immunology and the potential role of immune mechanisms in pathology observed with intraocular drug delivery.