INOCA was associated with significantly impaired endothelium-dependent relaxations and markedly attenuated EDH-mediated relaxation in resistance arteries compared to controls.
Observational (n=23)
Is endothelium-dependent hyperpolarisation impaired in resistance arteries of patients with INOCA compared to controls?
Systemic microvascular dysfunction in INOCA is characterized by a substantial reduction in EDH-mediated relaxation, highlighting endothelial function as a potential therapeutic target.
Abstract Background Ischemia with non-obstructive coronary artery disease (INOCA) is a clinically significant condition associated with adverse cardiovascular outcomes. Coronary microvascular dysfunction (CMD), a major contributor to myocardial ischemia in INOCA patients, remains underrecognized and poorly understood. The coronary endothelium modulates vascular tone through endothelium-derived relaxing factors (EDRFs), including vasodilator prostaglandins (PGs), nitric oxide (NO), and endothelium-dependent hyperpolarisation (EDH) factors, which act in a vessel size-dependent manner. While NO predominantly mediates vasodilation in large conduit arteries, EDH factors play a crucial role in regulating the tone of resistance arteries, and their dysfunctions are particularly relevant to CMD. Endothelial dysfunction, marked by diminished production or activity of EDRFs, is considered a key mechanism underlying CMD in INOCA. However, the specific contributions of individual EDRF components to CMD in INOCA remain unclear. Purpose This study aimed to elucidate the mechanism of microvascular dysfunction in INOCA patients, focusing on the relative contributions of EDRFs to endothelial function. Methods Patients undergoing interventional diagnostic procedure (IDP) for invasive coronary functional testing and subcutaneous fat tissue biopsy were prospectively recruited. Resistance arteries were isolated from the femoral fat samples and evaluated using wire myography. EDRF components were analyzed by assessing the inhibitory effects of indomethacin (Indo) for vasodilator PGs, Nω-nitro-L-arginine (L-NNA) for NO, and a combination of charybdotoxin (CTx) and apamin (Apm) for EDH-mediated relaxation. Results Among 23 patients enrolled (male/female 7/16, mean age 63 ± 12 years), resistance arteries (mean diameter: 286 μm) were successfully isolated and analyzed in 21 patients. Based on IDP findings, patients were classified into the INOCA group (n=17; 16 with vasospastic angina, 1 with microvascular angina) and the control group (n=4; patients with normal coronary physiology and no inducible ischemia). Baseline demographics, cardiovascular risk factors, and physiological parameters were comparable between the groups (Table). Acetylcholine induced concentration-dependent relaxations in precontracted resistance arteries in both groups; however, endothelium-dependent relaxations were significantly impaired in the INOCA group (Figure A). Notably, EDH-mediated relaxation was markedly attenuated in INOCA patients (Figures B-D), while vascular smooth muscle responses to sodium nitroprusside remained preserved. Conclusions Systemic microvascular dysfunction is prevalent in INOCA, with a substantial reduction in EDH-mediated relaxation, the primary EDRF component regulating microvascular tone. This finding provides new insights into CMD pathophysiology in INOCA and highlights the potential for endothelial function as a therapeutic target.
Onuma et al. (Sat,) conducted a observational in Ischemia with non-obstructive coronary artery disease (INOCA) (n=23). Ischemia with non-obstructive coronary artery disease (INOCA) vs. Normal coronary physiology and no inducible ischemia was evaluated on Endothelium-dependent relaxations and EDH-mediated relaxation in resistance arteries. INOCA was associated with significantly impaired endothelium-dependent relaxations and markedly attenuated EDH-mediated relaxation in resistance arteries compared to controls.