Step forward in understanding arterial disease

Further strides have been made into isolating the origin of cells that could lead to a greater understanding of what goes into the development of our blood circulating systems.

University of Lincoln Life Sciences academic Dr Rajiv Machado, with colleagues from the University of Cambridge, King’s College London and Papworth Hospital, has revealed the recent findings in a research letter to The American Journal of Respiratory and Critical Care Medicine.

Dr Machado’s main research area is in Pulmonary Arterial Hypertension (PAH) which is a progressive disorder characterised by abnormally high blood pressure (hypertension) in the pulmonary artery, the blood vessel that carries blood from the heart to the lungs. Symptoms are shortness of breath, dizziness, swelling (oedema) of the ankles or legs, chest pain and a racing pulse.

In this latest study, researchers investigated genetically identical twins, both of which had the genetic marker responsible for PAH. However, only one had the disorder which resulted in both a heart and lung transplant.

From this starting block, the team were able to investigate the origin of blood outgrowth endothelial cells (BOEC), which are stem cells and good candidates for vascular (re-) generating cell therapy. However, uncertainty remains as to the specific origin of these cells.

The researchers study of the twins and the mutation they both harboured enabled them to identify a marker to show that those stem cells, the BOECs, were very unlikely to have come from the heart or lungs.

Dr Machado said: “When the circulating BOECs were cultured from the new heart and lungs they still showed the mutation. Hence, they must have been produced in a different organ/s. The importance of this is that scientists are keen to know the origin of these cells both as a proxy for basic science and to provide an understanding of what goes into the development of our blood circulating systems. If we can in one fell swoop remove two organs as being contributory then we are another step closer to knowing where these cells come from.”

Leading academic on cardiovascular disease joins University

A scientist who discovered the genes that cause a disease linked to lung and heart failure has joined the team at the University of Lincoln’s School of Life Sciences.

Dr Rajiv Machado was previously a recipient of an independent British Heart Foundation fellowship in the Division of Genetics and Molecular Medicine, King’s College London.

He discovered the major gene that causes Pulmonary Arterial Hypertension (PAH) while in the third year of his PhD at the University of Leicester’s Department of Medical Genetics in 2000.

The condition is a progressive disorder characterised by abnormally high blood pressure (hypertension) in the pulmonary artery, the blood vessel that carries blood from the heart to the lungs. Symptoms are shortness of breath, dizziness, swelling (oedema) of the ankles or legs, chest pain and a racing pulse.

Dr Machado said: “Pulmonary Arterial Hypertension is fairly uncommon but extremely important in terms of understanding the way in which the lung works. Research in this area informs a huge number of more common diseases. It is currently incurable and has a high mortality rate. In terms of diagnosis and treatment the research I am doing opens up a number of new pathways we need to go down.”

The discovery of the PAH gene established Dr Machado’s name in the field of genetics and led to a surge in publications, foremost of which was the report of this work in the prestigious journal Nature Genetics. The findings were also awarded an American patent.

Dr Machado’s continuing research has since been featured in many other journals including one of the highest impact factor ranking publications in the world, The New England Journal of Medicine in which he and colleagues reported the identification of a second gene predisposing to forms of pulmonary hypertension. More recently, he reported the contribution of three more genes within the same pathway as underlying this spectrum of disease.

In 2008 Dr Machado was co-chairman of the Genetics and Genomics Committee at the third World Health Organisation (WHO) conference on pulmonary hypertension, producing a seminal paper in the Journal of American College of Cardiology (JACC). Dr Machado is attending the WHO summit in February 2013, for which he has already written a paper that will be combined with inputs from other eminent health experts.

The summit will seek to incorporate ideas and lessons from regional and international consultations, thereby building a powerful consensus around key issues and recommendations on health to feed into the global process that will start later in 2013.

Dr Machado said: “It will set the ground rules to our state of knowledge. Following the summit a seminal statement will be issued on where we are going as understood by the WHO. It really does inform clinical practice, basic science and treatment.”

In 2011, Dr Machado was integral to efforts that led to the discovery of a gene underlying the developmental disorder Adams-Oliver syndrome, characterised by limb and scalp defects, accompanied by a host of cardiac and vascular complications. This finding was noted by international publications including the American Journal of Medical Genetics which provided an editorial to mark the work.

On his appointment at the University of Lincoln, Dr Machado said: “The reason Lincoln is so appealing is that it is a university full of ambition with really good people at the helm. The institution has got the wherewithal to build a new research park which is going to be world-class. With the team of academics now in place at the University this is a place that is definitely moving forward fast and it is exciting to be a part of that.”