Saturday, May 28, 2022

Coronary Microvascular Disease: Study offers new insights

New research lifts the lid on cardiac microvascular dysfunction.

Coronary Microvascular Disease, also known as Microvascular dysfunction, is a non-obstructive coronary artery disease that causes the micro-arteries feeding the heart muscle not to work as they should. This affects the blood supply within the beating heart and other organs in the body, affecting people’s quality of life and life expectancy. 

Current heart scans can identify blockages in large coronary arteries, but they cannot show these tiny, hair-size micro-arteries in patients. This makes it challenging to diagnose poor myogenic tone, a normal intrinsic constriction of these micro-arteries in response to changing blood pressure

Myogenic tone controls blood flow distribution within the heart muscle and in other parts of the human body. 

A new study by the University of Bristol has shown abnormalities in the tiny blood vessels of human hearts. The abnormalities were seen in regions well beyond the large arteries with atherosclerotic blockages that trigger the need for stents or bypass surgery. 

Using tissue biopsies, scientists studied the function, structure, and alterations in pathways in the micro-arteries associated with the abnormalities in myogenic tone. 

The small heart samples (otherwise discarded) were collected from 88 patients who had no significant coronary artery blockages and were undergoing valvular cardiac surgery at the Bristol Heart Institute. Scientists also obtained cardiac samples from three human organ donors. 

Scientists found that 44 percent of the micro-arteries from patients had abnormal myogenic tone despite retaining their cell viability. This abnormality was associated with an excessive presence of a molecule called caldesmon 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 percent of patients, and all the organ donors and pigs. 

Professor Raimondo Ascione, NHS Consultant Cardiac Surgeon and Head of the TBRC at the University of Bristol, said: “It has been a pleasure to work with Professor Dora on this landmark study over the last seven years. 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.”

Kim Dora, Professor of Microvascular Pharmacology at the University of Oxford, explained: “I am so excited with the results of this study and the excellent teamwork with Professor Ascione in Bristol. 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.”

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, added“This study is the first to develop techniques to understand the links between the structure of micro-arteries and impaired myogenic tone, representing the outcome of years of painstaking work to develop the methods and apply them to micro-arteries from human hearts. The findings provide new information that will help to develop treatments for the many patients whose angina occurs without significant narrowing of their coronary arteries.”

Journal Reference: 
  1. Kim A Dora et al. Human coronary microvascular contractile dysfunction associates with viable synthetic smooth muscle cells. Doi: 10.1093/cvr/cvab218 
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