Research breakthroughs advance understanding of genetic causes of vascular disease

January 6, 2014 by Marie Daniels
Research breakthroughs advance understanding of genetic causes of vascular disease

(Medical Xpress)—The world's leading voices in the fight against pulmonary hypertension have compiled a special publication detailing the breakthrough research into the causes of this debilitating vascular disease.

Co-author Dr Rajiv Machado, from the School of Life Sciences, University of Lincoln, UK, attended the World Symposium on Pulmonary Hypertension in 2013 as an invited member of the symposium's genetics and genomics task-force.

Papers arising from this conference, which brought together the most respected clinicians and scientists in the field, have now been compiled in a special edition of Journal of the American College of Cardiology.

The symposium, which discussed several forms of resistance in lung vessels including those associated with common disorders such as and HIV, resulted in a powerful consensus around key issues and recommendations.

The replication and extension of these studies should serve to further define the genetic landscape surrounding vascular disease.

Dr Machado said: "The aim of the symposium was to report new information and how this could then be translated into clinical medicine by providing novel targets for therapy. The results have now been published as the definitive scientific consensus on this area of disease."

Dr Machado's main research focuses on (PAH), 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 include shortness of breath, dizziness, swelling (oedema) of the ankles or legs, chest pain and a racing pulse.

Dr Machado was part of a team that discovered the primary gene that causes PAH and has since gone on to investigate the disease pathway, isolating more contributory genetic mutations.

As reported at the symposium, Dr Machado's investigation of 300 patients with disparate forms of PAH - the largest study of its kind - resulted in the identification of three novel genes which appear to cause pulmonary dysfunction.  

A process called next generation sequencing (NGS) was used to exclude the likelihood of the observed genetic variation being present in the general population.

In a separate study, colleagues reported two additional genetic causes of disease present only in PAH patients and, intriguingly, a genetic variant enriched among patients but present in all of us.

Dr Machado said taken together the findings presented promising new avenues for research.

"It is extremely rare to find this form of variation in a disease like this," he said.

"Identification of this alteration may provide a new target for PAH treatment. It has wide ranging significance to our understanding of lung disease. It all contributes to the genetic architecture of the disease and our understanding of what causes it."

Dr Machado is now working on population-specific genetic patterns, looking at two subsets of PAH, including an Indian group which has no family history of the disease. He will use next generation sequencing to drive a baseline genetic profile of this previously unstudied population.

Dr Machado will also carry out full DNA sequencing to interrogate the causes of childhood PAH, a particularly severe form of disease which is currently not well understood.

Explore further: Step forward in understanding arterial disease

More information: The full paper, "Genetics and genomics of pulmonary hypertension," can be viewed at content.onlinejacc.org/article … 790605&resultClick=3

Related Stories

Step forward in understanding arterial disease

July 16, 2013
The next step has been made into isolating the origin of cells linked to the progressive disorder Pulmonary Arterial Hypertension.

New genetic cause of pulmonary hypertension identified

July 24, 2013
Columbia University Medical Center (CUMC) scientists have identified new genetic mutations that can cause pulmonary arterial hypertension (PAH), a rare fatal disease characterized by high blood pressure in the lungs. The ...

Disruption of cellular signaling identified in pulmonary arterial hypertension

December 27, 2012
(Medical Xpress)—Impairment of a key signaling cascade in the pulmonary blood vessels plays an important role in pulmonary arterial hypertension, a Yale study has found. The study appears in the advance online publication ...

Pulmonary hypertension combination therapy may lead to greater disease burden

October 22, 2012
Patients with pulmonary arterial hypertension (PAH) receiving combination therapy with intravenous (IV) PGI2 may suffer from greater disease burden compared with those receiving monotherapy or combination therapy, excluding ...

Heart drugs ineffective in treating pulmonary arterial hypertension

May 18, 2011
Despite their beneficial effects in treating heart disease, neither aspirin nor simvastatin appear to offer benefit to patients suffering from pulmonary artery hypertension (PAH), according to a National Institutes of Health ...

Adempas approved to treat pulmonary hypertension

October 9, 2013
(HealthDay)—Adempas (riociguat) has been approved by the U.S. Food and Drug Administration to treat two types of pulmonary hypertension, characterized by high blood pressure in the arteries of the lungs.

Recommended for you

Could aggressive blood pressure treatments lead to kidney damage?

July 18, 2017
Aggressive combination treatments for high blood pressure that are intended to protect the kidneys may actually be damaging the organs, new research from the University of Virginia School of Medicine suggests.

Quantifying effectiveness of treatment for irregular heartbeat

July 17, 2017
In a small proof-of-concept study, researchers at Johns Hopkins report a complex mathematical method to measure electrical communications within the heart can successfully predict the effectiveness of catheter ablation, the ...

Concerns over side effects of statins stopping stroke survivors taking medication

July 17, 2017
Negative media coverage of the side effects associated with taking statins, and patients' own experiences of taking the drugs, are among the reasons cited by stroke survivors and their carers for stopping taking potentially ...

Study discovers anticoagulant drugs are being prescribed against safety advice

July 17, 2017
A study by researchers at the University of Birmingham has shown that GPs are prescribing anticoagulants to patients with an irregular heartbeat against official safety advice.

Protein may protect against heart attack

July 14, 2017
DDK3 could be used as a new therapy to stop the build-up of fatty material inside the arteries

Heart study finds faulty link between biomarkers and clinical outcomes

July 14, 2017
Surrogate endpoints (biomarkers), which are routinely used in clinical research to test new drugs, should not be trusted as the ultimate measure to approve new health interventions in cardiovascular medicine, according to ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.