Biomarkers for Improved Cardiovascular Disease Management – Acute Coronary Syndrome miRNAs
Cardiovascular diseases are defined by the loss of flexibility of a patient’s blood vessels, or an obstructed and diminished blood flow. This class of diseases is the #1 cause of death in the western world, accounting for one in three deaths in Israel and one in four deaths in the UK and in the US. Cardiovascular diseases include acute coronary syndrome (ACS), stroke, diabetes and metabolic syndrome, kidney failure, other cardiac events. In all of these diseases, a vital organ or tissue, such as the heart muscle, brain, or kidney, fails to receive oxygen and nutrition. This triggers a process of escalating inflammation that leads eventually to life-threatening organ collapse.
Associated with cardiovascular disease is atherosclerotic plaque. This plaque—which is made up of fat, cholesterol, calcium, cells and other substances—is present on the inner surfaces of the arteries of all people, but certain people are more prone to plaque accumulation than others. Over time, aggregated plaque accumulation obstructs blood flow to the limbs and can result in cell suffocation, organ failure and death. Furthermore, the outer surface of plaques can rupture and the subsequent avalanche of debris can rapidly block arteries and lead to cell death, heart attack, and stroke—which in a matter of minutes can lead to the loss of limb, heart function, higher level brain cognition, and all too often—in death. We can predict the risk of acute coronary syndrome for patient by taking a traditional electrocardiogram (ECG). However, the underlying mechanisms of cardiovascular disease are not fully known. Our ability to manage distinct forms of cardiovascular disease is hindered by the absence of knowledge.
The Dangoor Centre for Personalized Medicine researchers heading this project hypothesize that the missing link in our understanding of the biological process is a particular group of nucleic acids, mainly micro-RNAs. Some of these nucleic acids appear to be critical agents that escalate inflammation and promote the clogging of blood vessels. The presence of these molecules might be useful as biomarkers, allowing us to identify high-risk patients for early intervention. Other micro-RNAs seem to reduce swelling and inflammation and might therefore offer protection against onset of cardiovascular disease.
To explore these hypotheses, the Dangoor Centre teams have been characterizing the micro-RNAs and certain other nucleic acids found in the blood, cells, and plaque accumulations of patients belonging to distinct risk groups. They use sequencing and ECG readouts for this purpose, attempting to correlate the presence of these micro-RNAs with ECG aberrations indicative of acute coronary syndrome (namely elevated ST and non-elevated ST). The Dangoor Centre researchers are also seeking those micro-RNAs which are distinct for each patient group. If successful, these biomarkers will allow us to accurately predict the most likely cardiac event for each patient and intervene accordingly.
Some patients participating in this personalized treatment and research program come from unique, poorly investigated demographic populations such as the Druze in northern Israel. The Dangoor Centre for Personalized Medicine researchers are therefore also investigating the causes of the high rates of cardiovascular disease found in these groups.