Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

A collaborative paper from the De Val and Smart Groups has established multiple regulatory pathways responsible for the formation of blood vessels in the developing heart. In doing so they have identified a crucial pathway that is repressed in the adult heart after injury, which may hold the key to a new and improved strategy for repair.

Enhancer analysis tracks the formation of the coronary arteries during development

The growth of new blood vessels is crucially important for the repair of heart muscle after a heart attack. However, the adult heart is not capable of growing enough of the correct type of blood vessels after injury, which contributes to the damage sustained.

The reactivation of developmental pathways in the diseased heart is a long-term aim for cardiac regenerative medicine. However, the signalling and transcriptional pathways involved in coronary vessel development are not yet understood. It is also still unclear whether the processes regulating embryonic and neonatal coronary vessel growth in the healthy heart play any role during adult coronary vascular regeneration after damage.

In a paper published in Nature Communications, led by Associate Professors Sarah De Val and Nicola Smart, the research team have used a novel enhancer-led approach to identify the transcriptional pathways involved in the development of coronary vessels in the healthy heart. Their technique has allowed direct interrogation of the behaviour of these pathways after ischemic injury in both the regenerative neonatal heart and the non-regenerative adult heart. 

They have identified three different regulatory pathways in mice which direct the formation of blood vessels in the heart during development. Of these, the main pathway responsible for the formation of new blood vessels, the angiogenesis-associated VEGFA-MEF2 pathway, is active in the healthy adult heart but is repressed after heart injury.

 

The adult heart doesn't respond "appropriately" to myocardial infarction to repair its coronary vasculature using the pathways used in the embryo to build the vasculature, which are activated in the more regenerative neonatal heart following injury. With this insight, we're in a better position to start investigating why and how to target a more efficient repair
- Prof Smart

The hypothesis is that the blood vessels do not grow well enough to repair the damaged heart because the heart appears to be inhibiting the pathway that it most needs to be active in order to successfully heal. Their results suggest that reactivating this pathway may improve blood vessel growth after heart attack. They will use a recently awarded grant from the British Heart Foundation to determine if this is correct.

 

This paper identifies novel regulators of coronary vessel growth and reveals unsuspected variations in the mechanisms regulating coronary vessel growth depending on developmental stage and disease state, observations with significant implications to future strategies for cardiac regeneration. It also identifies a novel, druggable target for therapeutic manipulations of vascular growth in the adult ischemic heart. - Prof De Val

The full paperRegulatory pathways governing murine coronary vessel formation are dysregulated in the injured adult heart, is available to read here.

Similar stories

The effect of nuclear pH on cardiac gene expression

Research led by Dr Alzbeta Hulikova and Professor Pawel Swietach has, for the first time, described the potential regulation of nuclear acid-base chemistry in neonatal and adult cardiomyocytes, and explained its relevance in the context of heart physiology and pathology.

Study indicates reasons for decline in death rates from heart attacks

A new study involving Oxford Population Health researchers finds that both prevention and improved treatments have helped reduce deaths from heart attacks - but the relative importance of each varies by country, age and sex.

Review highlights impact of Long COVID on cardiovascular system

The wide-ranging effects of Long COVID and the associated issues for healthcare providers have been revealed in a new review of the major studies into the condition, which specifically highlights the impact of Long COVID on the cardiovascular system.

Commercial development of therapeutic anti-inflammatory peptide begins

An Oxford BHF CRE “Pump Priming” award to Professor Shoumo Bhattacharya and his research group led to a great return on investment with this exclusive licensing agreement for their innovative research.

London Marathon to fund De Val and Vieira Lab research as two of eight handpicked BHF projects

Two projects aimed at tackling heart failure led by Associate Professor Sarah De Val and Dr Joaquim Vieira are to be funded by the 2022 TCS London Marathon with the British Heart Foundation as its Charity of the Year. The BHF’s runners, who are raising £3 million in funding, will include De Val Lab postdoctoral researcher Dr Alice Neal.

Dr Qiang Zhang wins Society for Cardiovascular Magnetic Resonance Early Career Award 2022

Many congratulations to Dr Qiang Zhang, Oxford BHF CRE Transition Fellow, who has won a prestigious award for his work in developing a groundbreaking technology for detecting scar in the myocardium