Coronary microvascular dysfunction (CMD) refers to structural and functional
abnormalities of the microcirculation that impair myocardial perfusion. CMD plays
a pivotal role in numerous cardiovascular diseases, including myocardial ischemia
with non-obstructive coronary arteries, heart failure, and acute coronary
syndromes. This review summarizes recent advances in CMD pathophysiology,
assessment, and treatment strategies, as well as ongoing challenges and future
research directions. Signaling pathways implicated in CMD pathogenesis include
adenosine monophosphate-activated protein kinase/Krüppel-like factor
2/endothelial nitric oxide synthase (AMPK/KLF2/eNOS), nuclear factor erythroid
2-related factor 2/antioxidant response element (Nrf2/ARE), Angiotensin II (Ang
II), endothelin-1 (ET-1), RhoA/Rho kinase, and insulin signaling. Dysregulation
of these pathways leads to endothelial dysfunction, the hallmark of CMD.
Treatment strategies aim to reduce myocardial oxygen demand, improve
microcirculatory function, and restore endothelial homeostasis through mechanisms
including vasodilation, anti-inflammation, and antioxidant effects. Traditional
Chinese medicine (TCM) compounds exhibit therapeutic potential through
multi-targeted actions. Small molecules and regenerative approaches offer
precision therapies. However, challenges remain in translating findings to
clinical practice and developing effective pharmacotherapies. Integration of
engineering with medicine through microfabrication, tissue engineering and AI
presents opportunities to advance the diagnosis, prediction, and treatment of
CMD.