From the Guidelines
Endothelium injury initiates atherogenesis in the coronary arteries. This injury to the inner lining of blood vessels is the primary trigger that sets off the complex process of atherosclerosis. When the endothelium becomes damaged due to factors such as hypertension, smoking, diabetes, or high cholesterol, it allows lipids (particularly LDL cholesterol) to penetrate the arterial wall. This endothelial dysfunction leads to an inflammatory response where immune cells like monocytes adhere to the damaged area, migrate into the vessel wall, and transform into macrophages that engulf lipids to become foam cells. These foam cells form the early fatty streaks that eventually develop into atherosclerotic plaques. While clotting factors, inflammatory reactions, and scar tissue formation do play important roles in the progression of atherosclerosis, they are subsequent events that occur after the initial endothelial injury has already triggered the disease process, as supported by the study published in the European Heart Journal 1.
Some key points to consider in the development of atherosclerosis include:
- The role of plaque composition and vulnerability in the risk of plaque disruption, as noted in the study 1
- The importance of inflammation in plaque instability, with circulating levels of inflammatory markers such as C-reactive protein (CRP) correlating with the clinical course and outcome of an acute coronary syndrome 1
- The potential for endothelial injury to be triggered by various factors, including hypertension, smoking, diabetes, or high cholesterol, leading to the initiation of atherogenesis, as discussed in the context of cardiovascular disease research 1
Understanding the sequence of events in atherogenesis helps explain why controlling risk factors that protect endothelial integrity is crucial for preventing coronary artery disease. By prioritizing the protection of the endothelium, individuals can reduce their risk of developing atherosclerosis and subsequent coronary artery disease.
From the Research
Atherogenesis Initiation
The initiation of atherogenesis in the coronary arteries is a complex process involving multiple factors. The key factors that contribute to this process are:
- Endothelium injury: This is considered a primary event in the initiation of atherogenesis 2, 3. Endothelial dysfunction leads to impaired endothelium-dependent vasodilation, increased oxidative stress, and chronic inflammation.
- Acute inflammatory reaction: This reaction is also a crucial component of atherogenesis, as it promotes the adhesion of leukocytes, thrombosis, and cell proliferation 2, 3.
- Excess clotting factors and formation of scar tissues: While these factors play a role in the progression of atherogenesis, they are not considered primary initiators of the process.
Mechanisms of Atherogenesis
The mechanisms underlying atherogenesis involve:
- Endothelial cell activation (ECA): This is characterized by loss of vascular integrity, expression of leucocyte adhesion molecules, and change in phenotype from antithrombotic to prothrombotic 3.
- Impaired endothelium-dependent relaxation: This is due to decreased bioavailability of nitric oxide (NO) and increased release of oxygen-derived free radicals 2.
- Oxidative stress and inflammation: These factors contribute to the progression of atherogenesis and are associated with endothelial dysfunction 4, 5.
Clinical Implications
Endothelial dysfunction is a hallmark of atherosclerotic cardiovascular diseases and is associated with increased risk of cardiac events 4, 5. Understanding the mechanisms of atherogenesis and endothelial dysfunction is crucial for the development of effective therapeutic strategies. Pharmacotherapies targeting endothelial dysfunction, such as lipid-lowering drugs and antihypertensive drugs, have potential for treatment of cardiovascular diseases 5, 6.