Singapore – An international team of researchers, including scientists at A*STAR’s Institute of Medical Biology (IMB), has shed new light on how the circulatory system and blood vessels are formed in the embryo. The discovery lays the groundwork for the development of new vascular drugs and treatments. The study was reported in the life sciences journal, eLife.
Many diseases are characterised by abnormal or poor blood vessel formation. For example, chronic wounds are the result of insufficient blood vessel formation, while age-related macular degeneration is the result of abnormal expansion of blood vessels which interfere with normal processes. Blood vessel formation is also a critical step in the growth and spreading of cancerous tumours, as tumours require a dedicated blood supply to provide the nutrients for growth.
As such, discovering the underlying mechanisms of blood vessel formation is extremely critical to develop therapies targeting a wide range of illnesses, by either blocking or promoting blood vessel growth, depending on the illness.
In the embryo, blood vessels develop from cells called angioblasts, which first need to move to the correct place where the respective blood vessels will form. The aorta and cardinal vein, in particular, are the very first major vessels to be developed, so as to carry blood in and out of the heart. Traditionally, scientists have thought that the protein Vascular Endothelial Growth Factor (VEGF) was responsible for guiding the angioblasts to the midline of the body for blood vessel formation. As such, the majority of current treatments target VEGF.
In this study, however, scientists found that VEGF is in fact dispensable for angioblast migration. Instead, angioblasts need to produce the Apelin receptor protein, which forms part of an alternate signalling pathway. The Apelin receptor protein in turn needs to be activated by two hormones, Apelin and Elabela. The team further found that Elabela alone is sufficient for the movement process. However, in cases with insufficient Elabela, the Apelin hormone may compensate for this deficiency and still allow correct development.
The role of Apelin and Elabela in establishing the circulatory system makes them potential targets in future development of therapeutic applications for illnesses ranging from the various cancers, and cardiovascular diseases, to even metabolic diseases such as diabetes. Anti-Apelin and anti-Elabela drugs could potentially inhibit the growth of new blood vessels to counter disorders such cancer and diabetic retinopathy, the leading cause of new blindness in working adults in developed countries, including Singapore.
IMB Senior Principal Investigator Dr Bruno Reversade, one of the study’s authors, who also led the discovery of Elabela two years ago, stated, “I am very pleased that we have further uncovered a critical role of Elabela in the establishment of the circulatory system, following its discovery as a hormone essential for heart development in 2013. We will continue to investigate how it guides blood vessel growth, with the ultimate aim of tapping on its potential as a target to address human cardiovascular diseases.”
Professor Birgit Lane, Executive Director of IMB, said, “Having successfully identified two more hormones crucial for blood vessel formation, the team’s findings have illuminated the scientific community’s understanding of the formation process. Such new insight allows us to better combat the varied disorders characterised by vascular issues and paves the way for the development of more efficient and effective treatments.”
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About A*STAR’s Institute of Medical Biology (IMB)
IMB is one of the Biomedical Sciences Institutes of the Agency for Science, Technology and Research (A*STAR). It was formed in 2007, with a mission to study mechanisms of human disease in order to discover new and effective therapeutic strategies for improved quality of life.
IMB has 20 research teams working in three primary focus areas - stem cells, genetic disease, and skin biology. The teams work closely with clinical collaborators as well as industry partners, to target the challenging interface between basic science and clinical medicine. IMB’s strategic research topics are targeted at translational research to understand the mechanisms of human disease so as to identify new strategies for disease amelioration, cure and eradication and to improve health and wellbeing. Since 2011, IMB has also hosted the inter-research institute Skin Biology Cluster platform, and leads major strategic funding programs in rare genetic diseases and in skin biology. In 2013 IMB became a founding institute of the Skin Research Institute of Singapore.
For more information about IMB, please visit www.imb.a-star.edu.sg.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.
As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.
We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and Research Institutes, the wider research community and industry. A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities primarily located in Biopolis and Fusionopolis.
For more information on A*STAR, please visit www.a-star.edu.sg.
