Deciphering the Genetic Code of Heart Health
By Manasvini Kala
When we think about heart diseases, cholesterol-filled diets, lack of exercise, and smoking often come to mind. These are the usual suspects of heart disease. However, a recent medical breakthrough takes us deeper into a potential root cause that has been in our DNA long before lifestyle choices have come into play.
A fascinating discovery exploring the genetic foundations of coronary artery dominance (CAD) has emerged in medical research from the laboratories of Dr. Tim Assimes and Dr. Kristy Red-Horse. Although it may sound like medical jargon at first, coronary artery dominance represents something simple and vital: how blood is supplied to our heart.
The interest around coronary artery dominance stems from its small, but mighty role in our body's internal dynamics. Unlike factors we can control, such as diet or exercise, coronary artery dominance is something that is pre-determined through genetics, offering a new understanding of heart disease risks.
Our hearts are supplied with blood by two main arteries: the right and left coronary arteries. Most individuals (80%) have a right-dominant coronary artery system, while others have a left-dominant or balanced system. Recent research highlighted the role of a gene called CXCL12, which has been previously implicated in heart disease and could potentially be the key to new preventive strategies. Through a comprehensive analysis involving tens of thousands of participants, scientists have linked variations in this gene to different patterns of coronary artery dominance. The CXCL12 gene makes a protein, that acts as a signal, to direct where cells should go during early heart development. This signaling is crucial for forming paths that our coronary arteries will follow, ultimately determining whether we have a right or left-dominant coronary artery system. Variations in this gene affect not just how these pathways are built, but might also influence the risk of heart problems later in life. Understanding how CXCL12 influences and affects coronary artery dominance offers a glimpse into a future where heart disease could be predicted and prevented with precision.
The research team delved deep into the genetics of coronary artery dominance and found that CXCL12 doesn't act alone; it's part of a network, a conversation within our cells that guides how our coronary arteries develop and function. By understanding the secrets behind this network, scientists can identify who might be at greater risk for heart disease and why.
But why does this matter? Knowing your coronary artery dominance could help create a unique prevention plan for your DNA. This is not meant to be generic advice to eat less and move more; it's about personalized medicine that understands your genetics specifically and how it influences your heart health.
As we learn more about the genetic factors that influence conditions like coronary artery dominance, we inch closer to a future where heart disease could be caught in its earliest, most preventable stages.
Q&A! with Dr. Themistocles Assimes
How can your findings about CXCL12 and coronary artery dominance be used in clinical settings? How might this knowledge help in treating coronary artery disease?
Dr. Assimes: Knowing your dominance pattern right now doesn’t really help from a prevention standpoint and we also would not determine that using genetics but rather some form of non-invasive imaging if we really wanted to know. Perhaps the only person who would want to know is any interventional cardiologist ahead of the revascularization procedure for CAD such as a PCI (Percutaneous Coronary Intervention) but even for those procedures, they are used to just getting the information during the angiogram part of the procedure. The clinical utility of knowing someone’s genetics of dominance is not well described in our pre-print but will be much better described in our next version of this manuscript – in the short term there is not much utility in the clinic for reasons mentioned above. In the long term, it has to do more with translating a better understanding of the mechanisms of dominance to a better understanding how coronary arteries form and grow and migrate, and then using that information to hopefully create “medical revascularization” opportunities for people with really advance CAD and multiple blocked arteries that are actually not amenable to PCI or CABG (or where such procedures are extremely high risk of failure and complications).
Full Research Publication:
https://www.medrxiv.org/content/10.1101/2023.10.27.23297507v1.full-text
Figure: CXCL12 influences coronary artery dominance in the developing heart.