What is unstable angina?
Unstable angina, also known as acute coronary syndrome (ACS), is a serious and potentially life-threatening condition characterized by chest pain or discomfort that occurs at rest, with minimal exertion, or unpredictably, and is often indicative of an impending heart attack (myocardial infarction). Unstable angina is considered a medical emergency and requires prompt evaluation and treatment.
The underlying cause of unstable angina is usually the rupture or erosion of atherosclerotic plaques in the coronary arteries, which supply oxygen-rich blood to the heart muscle. When a plaque ruptures or erodes, it can lead to the formation of a blood clot (thrombus) that partially or completely blocks the flow of blood through the affected coronary artery. This reduction in blood flow deprives the heart muscle of oxygen, leading to ischemia (a lack of oxygen), which manifests as chest pain or discomfort known as angina.
What is the relationship between unstable angina and oxidative stress?
The relationship between unstable angina and oxidative stress is intertwined, with oxidative stress playing a significant role in the pathophysiology of unstable angina and its progression to acute coronary events such as myocardial infarction (heart attack). Here’s how oxidative stress contributes to unstable angina:
- Endothelial Dysfunction: Oxidative stress can impair the function of the endothelium, the inner lining of blood vessels, leading to endothelial dysfunction. This dysfunction reduces the ability of the endothelium to produce and release vasodilators such as nitric oxide (NO) and prostacyclin, which help regulate vascular tone and maintain blood flow. Endothelial dysfunction results in vasoconstriction, increased vascular tone, and reduced vasodilation, leading to reduced coronary blood flow and increased susceptibility to coronary artery spasm and thrombosis, contributing to unstable angina.
- Inflammation and Atherosclerosis: Oxidative stress promotes inflammation within the arterial wall, contributing to the initiation and progression of atherosclerosis, a condition characterized by the buildup of plaque (fatty deposits) in the arterial walls. Inflammatory cytokines, chemokines, and adhesion molecules produced in response to oxidative stress recruit immune cells (such as monocytes and macrophages) to the arterial wall, where they contribute to the formation of atherosclerotic plaques. These plaques can become unstable and prone to rupture or erosion, leading to the formation of blood clots (thrombosis) and the onset of unstable angina.
- Platelet Activation and Thrombosis: Oxidative stress promotes platelet activation and aggregation, leading to the formation of blood clots within the coronary arteries. ROS can activate platelets directly and induce the release of pro-thrombotic factors, such as thromboxane A2 and adenosine diphosphate (ADP), which enhance platelet aggregation and thrombus formation. Platelet activation and thrombosis contribute to the occlusion of coronary arteries, leading to myocardial ischemia and unstable angina.
- Mitochondrial Dysfunction: Oxidative stress can disrupt mitochondrial function within cardiac myocytes (heart muscle cells), impairing energy production and cellular metabolism. Mitochondrial dysfunction reduces the capacity of cardiac myocytes to cope with ischemic stress and increases their susceptibility to ischemia-induced injury and cell death, contributing to myocardial ischemia and unstable angina.
- Antioxidant Defenses: Imbalance between ROS production and antioxidant defenses in the coronary arteries can contribute to oxidative stress and endothelial dysfunction in unstable angina. Reduced levels of antioxidants, such as superoxide dismutase, catalase, and glutathione, compromise the ability of the arterial wall to neutralize ROS and protect against oxidative damage, exacerbating vascular dysfunction and thrombosis.
Overall, oxidative stress plays a central role in the pathogenesis of unstable angina by promoting endothelial dysfunction, inflammation, atherosclerosis, platelet activation, thrombosis, and mitochondrial dysfunction in the coronary arteries.