From the Guidelines
Endothelial cells in coronary microvascular dysfunction (CMD) become damaged primarily through impaired endothelium-dependent arterial vasodilatation with decreased nitric oxide production, as well as increased levels of plasma endothelin that correlate with impaired coronary microvascular dilation. According to the most recent guidelines, including the 2024 ESC Guidelines for the management of chronic coronary syndromes 1, microvascular angina is caused by structural or functional changes in the coronary microvasculature, leading to impaired coronary flow reserve (CFR) and/or reduced microcirculatory conductance, and/or abnormal vasoconstriction of coronary arterioles.
Key factors associated with CMD include smoking, age, diabetes, hypertension, and dyslipidaemia, as outlined in the 2024 ESC guidelines 1. Additionally, inflammatory conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, as well as psychosocial stress, have been linked to microvascular angina. The 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction also highlights the role of impaired endothelium-dependent arterial vasodilatation and increased sensitivity to sympathetic stimulation in the pathogenesis of syndrome X, a condition characterized by angina or angina-like discomfort with exercise, ST-segment depression on exercise testing, and normal or nonobstructed coronary arteries on arteriography 1.
The mechanisms of endothelial damage in CMD are multifactorial and often synergistic, involving oxidative stress, chronic inflammation, metabolic factors, physical factors like hypertension, aging, and genetic predisposition. The damaged endothelium loses its ability to regulate vascular tone, becoming less responsive to vasodilatory signals and more prone to vasoconstriction, which ultimately impairs myocardial perfusion and contributes to symptoms like angina despite normal coronary arteries. The 2024 ESC guidelines 1 emphasize the importance of considering these factors in the diagnosis and management of microvascular angina, highlighting the need for a comprehensive approach to address the underlying causes of endothelial damage in CMD.
From the Research
Endothelial Cell Damage in Coronary Microvascular Dysfunction
Endothelial cells play a crucial role in maintaining the structural integrity and microcirculation function of the coronary microvasculature. However, various factors can contribute to endothelial injury and dysfunction, leading to coronary microvascular disease (CMD) 2.
Factors Contributing to Endothelial Cell Damage
Several factors can damage endothelial cells, including:
- Diabetes, hypertension, hyperlipidemia, and obesity, which can contribute to endothelial injury and arteriolar vasomotor dysfunction 2
- Inflammation, oxidative stress, insulin resistance, and tissue ischemia, which can dysregulate coronary endothelial homeostasis and arteriolar vasomotor function 2
- Impaired mitochondrial quality control (MQC) in endothelial cells, which can lead to EC injury and dysfunction 3
- Chronic low-grade inflammation, which is involved in coronary atherosclerosis and can lead to coronary microvascular dysfunction 4
Mechanisms of Endothelial Cell Damage
The mechanisms of endothelial cell damage in coronary microvascular dysfunction involve:
- Reduced endothelial function, which can be measured using techniques such as flow-mediated dilatation (FMD) of the brachial arteries 5
- Insufficient or uncontrolled activation of endothelial autophagy, which can facilitate the pathogenesis of CMD in diverse CVDs 6
- Disturbances in the coronary microvasculature, which can clinically manifest as diminished coronary flow reserve, a known independent risk factor for cardiac death 2