Co-immobilization of CD133 antibodies, vascular endothelial growth factors, and REDV peptide promotes capture, proliferation, and differentiation of endothelial progenitor cells

Abstract Background Chronic heart failure (CHF) remains a leading cause of morbidity and mortality and it is characterized by vascular endothelial dysfunction. During the last decades, endothelial progenitor cells (EPCs) are being used as an index of the endothelium restoration potential, therefore reflecting the vascular endothelial function. Exercise training has been shown to stimulate the mobilization of EPCs at rest in CHF patients. However, the effect of exercise training on the acute respond of EPCs after maximum exercise in CHF patients remains unknown. Purpose The purpose of the study was to assess the effect of a cardiac rehabilitation (CR) program on the acute respond of EPCs after maximum exercise in patients with CHF. Methods Forty-four consecutive patients (35 males) with stable CHF [mean±SD, Age (years): 56±10, BMI (kg/m2): 28.7±5.2, EF (%): 33±8, Peak VO2 (ml/kg/min): 18.4±4.4, Peak work rate (watts): 101±39] enrolled a 36-session CR program based on high-intensity interval exercise training. All patients underwent an initial symptom limited maximal cardiopulmonary exercise testing (CPET) on an ergometer before the CR program and a final maximal CPET after the CR program. Venous blood was drawn before and after each CPET. Five circulating endothelial populations were identified and quantified by flow cytometry; CD34+/CD45-/CD133+, CD34+/CD45-/CD133+/VEGFR2, CD34+/CD133+/VEGFR2, CD34+/CD45-/CD133- and CD34+/CD45-/CD133-/VEGFR2. EPCs values are expressed as cells/million enucleated cells in medians (25th-75th percentiles). Results The acute mobilization of EPCs after the final CPET was higher than after the initial CPET in 4 out of 5 circulating endothelial populations. Most specifically, difference of the acute mobilization of CD34+/CD45-/CD133+ cells [initial CPET: 25 (15–46) vs final CPET: 49 (26–71), p=0.002], CD34+/CD45-/CD133+/VEGFR2 cells [initial CPET: 3 (2–5) vs final CPET: 8 (5–12), p<0.001], CD34+/CD45-/CD133- cells [initial CPET: 129 (52–338) vs final CPET: 250 (129–518), p=0.03] and CD34+/CD45-/CD133-/VEGFR2 cells [initial CPET: 2 (1–4) vs final CPET: 6 (3–9), p<0.001] increased after the final CPET. The acute mobilization of CD34+/CD133+/VEGFR2 cells [initial CPET: 3 (−1–7) vs final CPET: 5 (0–15), p=0.441] did not differ between the 2 CPETS. Conclusion A 36-session cardiac rehabilitation program increases the acute respond of endothelial progenitor cells after maximum cardiopulmonary exercise training in patients with chronic heart failure, therefore indicating the beneficial effect of exercise training on the vascular endothelial function. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning” in the context of the project

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Intravitreal anti‐vascular endothelial growth factors, panretinal photocoagulation and combined treatment for proliferative diabetic retinopathy: a systematic review and network meta‐analysis

Acta Ophthalmologica ◽

10.1111/aos.14681 ◽

2020 ◽

Author(s):

Matteo Fallico ◽

Andrea Maugeri ◽

Andrew Lotery ◽

Antonio Longo ◽

Vincenza Bonfiglio ◽

...

Keyword(s):

Systematic Review ◽

Diabetic Retinopathy ◽

Growth Factors ◽

Proliferative Diabetic Retinopathy ◽

Meta Analysis ◽

Combined Treatment ◽

Vascular Endothelial Growth Factors ◽

Panretinal Photocoagulation ◽

Vascular Endothelial ◽

Endothelial Growth Factors

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Proteolytic Cleavages in the VEGF Family: Generating Diversity among Angiogenic VEGFs, Essential for the Activation of Lymphangiogenic VEGFs

Biology ◽

10.3390/biology10020167 ◽

2021 ◽

Vol 10 (2) ◽

pp. 167

Author(s):

Jaana Künnapuu ◽

Honey Bokharaie ◽

Michael Jeltsch

Keyword(s):

Growth Factors ◽

Molecular Level ◽

Specific Antigen ◽

Receptor Activation ◽

Vascular Endothelial Growth Factors ◽

Vascular Endothelial ◽

Turn On ◽

C And N ◽

Proteolytic Cleavages ◽

Endothelial Growth Factors

Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymphangiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptors. At least five different proteases mediate the activating cleavage of VEGF-C: plasmin, ADAMTS3, prostate-specific antigen, cathepsin D, and thrombin. All of these proteases except for ADAMTS3 can also activate VEGF-D. Processing by different proteases results in distinct forms of the “mature” growth factors, which differ in affinity and receptor activation potential. The “default” VEGF-C-activating enzyme ADAMTS3 does not activate VEGF-D, and therefore, VEGF-C and VEGF-D do function in different contexts. VEGF-C itself is also regulated in different contexts by distinct proteases. During embryonic development, ADAMTS3 activates VEGF-C. The other activating proteases are likely important for non-developmental lymphangiogenesis during, e.g., tissue regeneration, inflammation, immune response, and pathological tumor-associated lymphangiogenesis. The better we understand these events at the molecular level, the greater our chances of developing successful therapies targeting VEGF-C and VEGF-D for diseases involving the lymphatics such as lymphedema or cancer.

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Study of Microvessel Density and the Expression of Vascular Endothelial Growth Factors in Adrenal Gland Pheochromocytomas

International Journal of Endocrinology ◽

10.1155/2014/104129 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Magdalena Białas ◽

Grzegorz Dyduch ◽

Joanna Dudała ◽

Monika Bereza-Buziak ◽

Alicja Hubalewska-Dydejczyk ◽

...

Keyword(s):

Growth Factors ◽

Microvessel Density ◽

Antiangiogenic Therapy ◽

Prognostic Significance ◽

Operation Technique ◽

Vascular Endothelial Growth Factors ◽

Vascular Endothelial ◽

Vascular Architecture ◽

Laparoscopic Operation ◽

Endothelial Growth Factors

Angiogenesis (neoangiogenesis), a process of neovascularization, is an essential step for local tumor growth and distant metastasis formation. We have analysed angiogenesis status: vascular architecture, microvessel density, and vascular endothelial growth factors expression in 62 adrenal pheochromocytomas: 57 benign and 5 malignant. Immunohistochemical evaluation revealed that vascular architecture and vessel density are different in the central and subcapsular areas of the tumor. Furthermore, we have observed a strong correlation between number of macrophages and microvessel density in the central and subcapsular areas of the tumor and between the expression of VEGF-A in tumor cells and microvessel density in central and subcapsular areas of the tumor. Secondary changes in these tumors influence the results and both vascular architecture and microvessel density are markedly disturbed by hemorrhagic and cystic changes in pheochromocytomas. These changes are partially caused by laparoscopic operation technique. However, no differences in vascular parameters were found between pheochromocytomas with benign and malignant clinical behavior. Our observation showed that analysis of angiogenesis, as a single feature, does not help in differentiating malignant and benign pheochromocytomas and has no independent prognostic significance. On the other hand, high microvessel density in pheochromocytoma is a promising factor for antiangiogenic therapy in malignant cases.

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