Discoveries about abnormalities in the tiny blood vessels of human hearts should lead to new treatments, according to a UK study.
Researchers from the Universities of Bristol and Oxford hope their findings will lead to the development of new treatments for people with angina-like symptoms without blockages, if they are recovering from a heart attack or have unexplained heart failure.
Although heart scans can identify blockages in large coronary arteries, they are unable to show tiny, hair-size micro-arteries, making it impossible to diagnose poor myogenic tone, which is thought to develop independent of disease in the larger arteries.
In this BHF-funded study, which has taken seven years, the team, led by Professor Raimondo Ascione at the University of Bristol and Professor Kim Dora at the University of Oxford used tissue biopsies to study the function, structure and alterations in pathways in the micro-arteries that link to abnormalities in myogenic tone.
They took small heart samples from 88 patients with no large coronary artery blockages and undergoing valvular cardiac surgery at the Bristol Heart Institute, and also obtained cardiac samples from three human organ donors from the Newcastle Institute of Transplantation Tissue Biobank and 45 pigs treated at the University of Bristol Translational Biomedical Research Centre (TBRC).
The results, published recently in Cardivascular Research, showed that 44% of the micro-arteries from patients had abnormal myogenic tone, despite retaining their cell viability.
This abnormality was associated with an excessive presence of caldesmon, a molecule within the muscle cells in the wall of the abnormal micro-arteries, and with poor alignment of these contracting cells compared to micro-arteries with normal myogenic tone from the other 66% of patients, and all the organ donors and pigs.
The researchers say their findings provide new insights on coronary microvascular dysfunction that could predate the development of clinically known heart disease.
Professor Raimondo Ascione, NHS consultant cardiac surgeon and Head of the TBRC at the University of Bristol, said: “No study had focused on ex vivo poor myogenic tone of the cardiac microcirculation before. These tiny arteries are sited deep within the cardiac wall, well beyond the blocked arteries we treat in the NHS with stents or bypass surgery and cannot be seen with a naked eye.
“Our study lifts the lid on cardiac microvascular dysfunction. It could help to develop new treatments to help patients with angina-like symptoms without coronary blockages, or those recovering from a heart attack or unexplained heart failure.”
Professor Kim Dora, professor of microvascular pharmacology at the University of Oxford, said she was excited by the results, adding: “Not only will our findings enhance the development of new medical treatments and possibly new patient imaging modalities, but they represent a new ex-vivo research model for thousands of scientists globally working on microvascular dysfunction in the heart and other organs.”
There is now a new area of research that confirms thousands of patients, mostly postmenopausal women, have angina-like symptoms despite their coronary angiogram showing no obvious blockages of the large epicardial arteries in the heart that are usually treated with stent or bypass.
Dora KA, Borysova L, Ye X et al. Human coronary microvascular contractile dysfunction associates with viable 2 synthetic smooth muscle cells. Cardiovascular Research June 2021.
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