Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi in Psoriasis and Psoriatic Arthritis, 2017
VEGF and the soluble form of its receptor are found in both the skin lesion and serum of patients. In one study, VEGF and soluble VEGFR1 (sFlt1) in the sera of patients were respectively two and four times higher than in healthy controls and demonstrated significant correlation with the Psoriasis Area and Severity Index (PASI), but not soluble VEGFR2 (sKDR) (Flisiak et al. 2010). The isoform of VEGF that has been most studied in psoriasis is VEGFA, but VEGFC and, to a small extent, VEGFD have also been found in psoriasis. VEGFC can play roles in both angiogenesis and lymphangiogenesis. VEGFD is usually implicated in lymphangiogenesis. Keratinocytes, neutrophils, mast cells, macrophages and possibly fibroblasts, smooth muscle cells, and so forth, express VEGF in psoriasis. Keratinocytes from psoriatic lesions are known to express several VEGFA splice forms, including VEGF121 (the most common), followed by VEGF189, 165, and a little 145 (Man et al. 2008). One of the smallest splice forms of VEGFA, VEGF121 is weakly acidic and non–heparin binding (compared with the larger basic ones), and thus freely diffusible, and forms a wide shallow gradient in contrast with 189, which is strictly localized, and 165, which forms a gradient steep enough to form tip cells. VEGF121 is also the most abundant form in both psoriasis lesions and uninvolved skin in psoriasis patients compared with controls (Henno et al. 2009). This is a potential explanation as to why so much VEGF does not cause an increase in branching angiogenesis.
Lymphatic disorders
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
Most of the proteins encoded by these genes belong to the VEGF-C-VEGFR-3 ligand-receptor signalling complex and RAS/MAPK axis. The VEGF-C-VEGFR-3 signalling pathway is a major regulator of lymphangiogenesis. Downstream, transcription factors such as FOXC2 and ITGA9 play a major role in the development of valves in the lymphatic vessels. Mutations in the FLT4 gene that encodes VEGFR-3 protein were the first to be discovered and affect the tyrosine-kinase domain of the receptor, causing congenital primary lymphoedema. Mutations in the genes encoding the RAS/MAPK pathway cause several rare genetic conditions often called RASopathies. All RASopathies have some common clinical features such as distinct facial features and cardiac abnormalities. In addition to lymphoe- dema, these patients can also present with chylothorax and chylous ascites.
Imaging Angiogenesis
George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos in Handbook of Small Animal Imaging, 2018
Formation of new vascular networks, in which new capillaries sprout from preexisting vessels, is termed angiogenesis and it represents a biological process that is orchestrated by a number of angiogenic factors and inhibitors (Carmeliet and Jain 2000). Angiogenesis is distinct from arteriogenesis and lymphangiogenesis, and is naturally implicated in numerous biological processes, such as reproduction (female reproductive cycle and embryogenesis), wound healing, and tissue remodeling. This process is usually focal and controlled by the actions of angiogenic inhibitors, thus is self-limiting in time (Folkman 2007). On the other hand, there are numerous macro and microvascular disorders characterized by either an excess (i.e., ocular and inflammatory disorders) or an insufficient number of blood vessels (i.e., ischemic heart disease or preeclampsia). These pathologies have recently become a focus of intense research efforts directed at developing (1) novel imaging techniques for early diagnosis and prognostication, and (2) novel individualized therapeutic strategies focused on the modulation of the angiogenic process (Sinusas 2004; Dobrucki et al. 2010a; Dobrucki and Sinusas 2010).
Adenosine A2a receptor promotes lymphangiogenesis and lymph node metastasis
Published in OncoImmunology, 2019
Bertrand Allard, Isabelle Cousineau, David Allard, Laurence Buisseret, Sandra Pommey, Pavel Chrobak, John Stagg
Lymphangiogenesis is increasingly recognized as an important process favoring the development and the progression of multiple inflammatory disorders including cancer.33 In various human tumors, the accumulation of intra or peri-tumoral lymphatic vessels has been consistently documented and very often associated with lymph node metastasis and worse prognosis for patients.32,49-54Very recently, the contribution of tumor-associated lymphangiogenesis and lymph node metastasis for the actual establishment of distant metastasis was distinctly evidenced in two landmark studies.55,56 Lymphangiogenesis was also shown to occur in distant organs with established metastases where it promoted further spread of the tumor cells to other organs.57 Supporting the clinical relevance of our findings, we found that expression of Adora2a and adenosine-generating ectonucleotidases were positively correlated with the levels of lymphatic or pro-lymphangiogenic markers such as Lyve1, Pdpn or Vegfc, in several types of human tumors. In this context, our findings are highly relevant as they identify a novel pathway that could be targeted to block tumor-associated lymphangiogenesis and sentinel lymph node metastasis. With various A2a receptors antagonists currently under clinical evaluation for cancer immunotherapy, our results highlight a new tumor-promoting function of A2a signaling in the TME and thus further support the development of A2a inhibitors and adenosine-targeting agents for cancer treatment.
M2b macrophages stimulate lymphangiogenesis to reduce myocardial fibrosis after myocardial ischaemia/reperfusion injury
Published in Pharmaceutical Biology, 2022
Cuiping Wang, Yuan Yue, Suiqing Huang, Keke Wang, Xiao Yang, Jiantao Chen, Jiaxing Huang, Zhongkai Wu
Macrophages produce VEGFC to promote lymphangiogenesis (Watari et al. 2008; Yamashita et al. 2009). The phenotypic heterogeneity of macrophages relates to unique functions specific to the local microenvironment. In a mouse model of renal fibrosis, a VEGFR3 inhibitor down-regulated the expression of VEGFC by M1 macrophages to reduce lymphangiogenesis and ameliorate tubule-interstitial fibrosis. M1 macrophages can cause chronic inflammation-induced lymphangiogenesis, which worsens renal fibrosis (Hwang et al. 2019). Our previous study showed that M2b macrophages can significantly reduce the level of cardiac troponin I (cTnI) and the infarct area during the early period of MI/RI (Yue et al. 2017). Whether M2b macrophages can inhibit long-term cardiac fibrosis after MI/RI has not been studied.
Isotretinoin does not alter VEGF-A and VEGF-C levels: do retinoids behave differently in dose-dependent and/or in vivo/in vitro conditions?
Published in Cutaneous and Ocular Toxicology, 2020
Erhan Ayhan, Eşref Araç, Özgür Aslan
Vascular endothelial growth factor (VEGF) family consists of VEGF-A (known as VEGF), VEGF-B, VEGF-C, VEGF-D and placental growth factor (PlGF). VEGF-A is an important regulator involved in the developmental vasculogenesis, angiogenesis and differentiation of progenitor endothelial cells. VEGF-B and PlGF induce angiogenesis in normal tissues, but their activity is much weaker than that of VEGF-A1,2. VEGF-C and VEGF-D are produced from their precursors and regulate lymphangiogenesis3,4. There are publications reporting that retinoids including isotretinoin (13-cis-retinoic acid) are successful in lymphangioma circumscriptum, angiolymphoid hyperplasia with eosinophilia, diffuse dermal angiomatosis, and Kaposi’s sarcoma5–12. In some publications, the effect of success is claimed to be the inhibitory effect on VEGF5,6. However, in the literature, it is seen that various forms of retinoids have different results on VEGF-A and VEGF-C levels when tested at different dosages, in different diseases and under different conditions such as in vivo or in vitro.13–18 However, there is no study on using only isotretinoin and its effect on VEGF-A and VEGF C in humans. Therefore, we aimed to investigate whether isotretinoin commonly used in dermatology has an effect on VEGF-A and VEGF-C.
Related Knowledge Centers
- Angiogenesis
- Edema
- Lymphatic Vessel
- Metastasis
- Physiology
- Metabolism
- Immunity
- Neoplasm
- Homeostasis
- Rheumatoid Arthritis